卵磷脂对砷染毒非洲绿猴肾细胞细胞膜损伤的作用

目的 观察卵磷脂对亚砷酸钠(NaAsO2)染毒非洲绿猴肾细胞(Vero)细胞膜损伤的作用.方法 将体外培养Vero细胞分为4组:对照组(生理盐水)、砷模型组(2.20 mg/L NaAsO2)、卵磷脂高剂量+砷干预组(53.33 mg/L卵磷脂+2.20 mg/L NaAsO2)、卵磷脂低剂量+砷干预组(13.32 mg/L卵磷脂+2.20 mg/L NaAsO2),每组6瓶细胞,每2天换液1次,培养120 h.采用分光光度法测定细胞膜Na+,K+-ATP酶活性,高效液相法测定细胞膜磷脂组分磷脂酰丝氨酸(PS)、磷脂酰乙醇胺(PE)、磷脂酰胆碱(PC)和神经鞘磷脂(SM).结果 对照组、砷模型组、卵磷脂高剂量+砷干预组、卵磷脂低剂量+砷干预组细胞膜Na+,K+-ATP酶活性分别为(O.962 ±0.081)×106、(0.544±0.037)×106、(0.647±0.043)×106、(0.550±0.020)× 106 U·kg-1·h-1,各组间比较,差异有统计学意义(F=43.58,P<0.01).与对照组比较,其他3组细胞膜Na+,K+-ATP酶活性明显降低(P均<0.05);与砷模型组比较,卵磷脂高剂量+砷干预组明显增高(P<0.05),而卵磷脂低剂量+砷十预组未见明显改变(P>0.05).与对照组[(0.087±0.003)、(0.127±0.053)、(0.588±0.105)、(0.07l±0.029)g/L]比较,砷模型组PS、PE、PC、SM水平[(0.051±0.018)、(0.073±0.030)、(0.240 4-0.038)、(0.047±0.121)g/L]均明显降低(P均<0.05);卵磷脂高剂量+砷干预组PS、PE、PCI(0.084±0.011)、(0.109±0.363)、(0.591±0.476)g/L]未见明显改变(P均>0.05),而SM[(0.057±0.004)g/L]明显降低(P<0.05);卵磷脂低剂量+砷干预组PS、PE、SM[(0.058±0.020)、(0.086±0.177)、(0.048±0.103)g/L]明显降低(P均<0.05),而PCI(0.521±0.098)g/L]未见明显改变(P>0.05).与砷模型组比较,卵磷脂高剂量+砷干预组PS、PE、PC、SM明显增高(P均<0.05);卵磷脂低剂量+砷干预组PS、PE、SM未见明显改变(P均>0.05),PC明显增高(P<0.05).结论 高剂量卵磷脂对砷染毒Vero细胞膜损伤具有一定的保护作用.

Abstract：

Objective To observe the lecithin's effect on membrane of African green monkey kidney cells (Vero) exposed to sodium arsenite(NaAsO2). Methods Vero cells cultured in vitro were divided into 4 groups:control group (saline), model group (2.20 mg/L NaAsO2), high eoncentration of lecithin and arsenic group (53.33mg/L lecithin + 2.20 mg/L NaAsO2), low eoncentration of lecithin and arsenic group( 13.32 mg/L lecithin + 2.20 mg/L NaAsO2), 6 bottles of cells in each group, medium was changed every 2 days, cultured for 120 h. Na+ ,K+-ATPase activities of membrane were measured by spectrophotometry, and membrane phospholipids composition including phosphatidylserine (PS), phosphatidylethano-lamine (PE), phosphatidylcholine (PC) and sphingmyelin (SM) were measured by high performance liquid chromatography (HPLC). Results The Na~, K+-ATPase activities of membrane of control group, model group, high concentration of lecithin and arsenic group, low concentration of lecithin and arsenic group were (0.962 ± 0.081) × 106, (0.544 ± 0.037) × 106, (0.647 ± 0.043) x 106, (0.550±Compared with control group, the Na+ ,K+-ATPase activities of other 3 groups were significantly reduced (all P < 0.05). Compared with model group, the Na+ ,K+-ATPase activity in high concentration of lecithin and arsenic group was significantly higher (P < 0.05),but in low concentration of lecithin and arsenic group did not change significantly (P > 0.05). Compared with control group[(0.087 ± 0.003), (0.127 ± 0.053), (0.588 ± 0.105),(0.071 ± 0.029)g/L], PS, PE, PC, SM levels in model group[(0.051 ± 0.018), (0.073 + 0.030), (0.240 ±0.038), (0.047 ± 0.121 )g/L] were significantly lower(all P < 0.05) ;PS, PE, PC in high concentration of lecithin and arsenic group[(0.084 ± 0.011), (0.109 ± 0.363), (0.591 ± 0.476)g/L] did not change significantly(all P > 0.05), but SM[(0.057 ± 0.004)g/L] significantly decreased(P < 0.05) ;PS, PE, SM levels of low concentration of lecithin and arsenic group[(0.058 ± 0.020), (0.086 ± 0.177), (0.048 ± 0.103)g/L] significantly reduced (all P < 0.05), the PC did not change significantly [(0.521±0.098 )g/L, P > 0.05]. Compared with model group,the levels of PS, PE, PC, SM in high concentration of lecithin and arsenic group were significantly higher(all P <0.05);PS, PE, SM levels in low concentration of lecithin and arsenic group did not change significantly(all P > 0.05), and PC was significantly higher(P < 0.05). Conclusions High concentration lecithin has certain protective effect on Vero cell membrane exposured to sodium arsenite.     

硒对氟致大鼠肾脏损伤保护作用的实验观察

目的 观察硒对氟致大鼠肾脏损伤的保护作用,探讨硒的最佳作用剂量及作用靶点.方法 断乳SD雄性大鼠80只,按体质量随机分8组,每组10只.对照组饮用自来水;染氟组饮用50 mg/L的氟化钠溶液;低、中、高硒组分别饮用0.375、0.750、1.500 mg/L的亚硒酸钠溶液;氟+低、中、高硒组分别饮用50 mg/L的氟化钠和0.375、0.750、1.500 mg/L的亚硒酸钠两两组合的溶液.染毒6个月后,测大鼠肾脏组织的氧化水平和核因子κB(NF-κB)的表达量.结果 染氟组大鼠体质量[(695.95±55.89)g]低于对照组[(782.69±56.12)g,P＜0.01],染氟组谷胱甘肽过氧化物酶(GSH-Px)活性[(55.86±5.09)U/mgprot]与对照组[(68.66±4.52)U/mgprot]比较,差异无统计学意义(P＞0.05),但有降低的趋势.染氟组大鼠总抗氧化能力(T-AOC)水平[(7.54±1.35)U/mgprot]低于对照组[(9.03±0.37)U/mgprot,P＜0.05],染氟组丙二醛(MDA)水平[(3.86±0.31)nmol/mgprot]高于对照组[(3.14±0.32)nmol/mgprot,P＜0.05].氟+高硒组GSH-Px活性[(74.99±8.41)U/mgprot]高于染氟组[(55.86±5.09)U/mgprot,P＜0.05],MDA水平[(3.17±0.20)nmol/mgprot]低于染氟组[(3.86±0.31)nmol/mgprot,P＜0.05].染氟组、高硒组和氟+低硒组的NF-κB的表达水平(0.360±0.015,0.367±0.007,0.376±0.006)高于对照组(0.312±0.022,P均＜0.05),氟+高硒组(0.312±0.005)低于染氟组(0.360±0.015,P＜0.05).结论 1.500 mg/L硒是本实验条件下硒对慢性氟中毒致大鼠肾脏损伤的最佳保护作用剂量,NF-κB可能是硒拮抗氟中毒的药物靶点.

Abstract：

Objective To explore the protective effect of selenium, an antioxidant, on fluoride-induced renal injury in rats and find out the optimal level of selenium against fluoride toxicity and its valid molecular target.Methods All 80 male weanling SD rats were randomly divided into 8 groups by body weight as follows: normal control group(drinking tap water), fluoride exposed group (drinking water containing 50 mg/L of NaF), low, middle,high selenium exposed groups(drinking water containing 0.375, 0.750, 1.500 mg/L of Na2SeO3) and low, middle,high Se-fluoride groups (drinking water containing both 50 mg/L NaF and three doses of Na2SeO3 as abovementioned, respectively). After 6 months, the rats were killed then the oxidation level and nuclear factor κB(NF-κB)expression level in kidney were measured. Results The weight of the fluoride exposed group[(695.95 ± 55.89 )g]was significantly deceased than the controls[(782.69 ± 56.12)g, P ＜ 0.01]. Glutathione peroxidase(GSH-Px)activity of fluoride exposed group[(55.86 ± 5.09)U/mgprot] was not significantly different but decreased. Tatal antioxidant capacity (T-AOC) activity in fluoride exposed group [(7.54 ± 1.35)U/mgprot] significantly decreased than the controls[(9.03 ± 0.37 )U/mgprot, P ＜ 0.05]. In addition, a significant increase of malondialdehyde ( MDA )in fluoride exposed group[(3.86 ± 0.31 )mnol/mgprot, P ＜ 0.05] was observed than the controls[(3.14 ± 0.32)nmol/mgprot, P ＜ 0.05]. GSH-Px activity of high Se-fluoride group[(74.99 ± 8.41 )U/mgprot] was significantly higher than the fluoride exposed group[(55.86 ± 5.09)U/mgprot, P ＜ 0.05] and its MDA level[(3.17 ± 0.20)nmol/mgprot] was lower than the fluoride exposed group[(3.86 ± 0.31 ) nmol/mgprot, P ＜ 0.05]. NF-κB expression levels of fluoride group, high selenium group and low Se-fluoride group(0.360 ± 0.015,0.367 ± 0.007,0.376 ± 0.006,respecyively) were obviously increased compared with the controls(0.312 ± 0.022, P ＜ 0.05); it was significantly lower in high Se-fluoride group(0.312 ± 0.005) than in fluoride exposed group(0.360 ± 0.015, P ＜ 0.05). Conclusions Na2SeO3 of 1.5 mg/L is the optimal dose against chronic fluorosis on kidney injury under this experimental condition.NF-κB is likely to be a target molecule of the selenium as an antagonist on fluorosis.     

亚砷酸钠对大鼠外周血淋巴细胞DNA损伤的研究

目的 研究亚砷酸钠(NaAsO2)染毒对大鼠外周血淋巴细胞DNA的损伤作用.方法 Wistar大鼠32只,体质量180～200 g,雌雄各半,按体质量随机分为4组,分别为0(对照)、0.05、0.15、0.45 mg/L NaAsO2染毒组,每组8只.大鼠自由饮用含不同剂量NaAsO2的水,每天测量体质量并记录水消耗量.连续染毒30 d后,眼眶静脉采血,应用单细胞凝胶电泳试验评价大鼠外周血淋巴细胞的损伤程度.结果 0.05、0.15、0.45mg/L染砷组大鼠的体质量增长[(121.00±38.57)、(120.62±42.80)、(125.38±48.68)g]和饮水量[(36.9±6.2)、(37.9±5.8)、(39.3±4.2)ml/d]与对照组[(119.25±47.27)g、(38.4±5.1)ml/d]比较,差异无统计学意义(F值分别为0.040、0.828,P均＞0.05).0.05、0.15、0.45 mg/L染砷组大鼠的外周血淋巴细胞拖尾率[46.25%(185/400)、57.00%(228/400)、64.00%(256/400)]、彗星尾长[(32.89±17.18)、(58.74±36.28)、(77.55±35.73)μm]、尾矩[(6.29±3.74)、(11.20±9.64)、(17.30±12.60)μm]显著高于对照组[39.25%(157/400)、(18.73±15.83)、(2.61±1.05)μm,P均＜0.01];随着染砷剂量的增加,淋巴细胞拖尾率、彗星尾长和尾矩均呈上升趋势.结论 低剂量砷染毒可引起大鼠外周血淋巴细胞DNA的损伤.

Abstract：

Objective To explore the DNA damage in peripheral blood lymphocytes of rats exposed to sodium arsenite. Methods Thirty-two Wistar rats, weighing 180 - 200 g, equal male and female, were randomly divided into 4 groups, 8 in each group. Sodium arsenite 0(control) ,0.05,0.15,0.45 mg/L were given through drinking water for 30 days. Body weight and drinking water consumption were measured every day. Blood were collected and DNA damage in peripheral blood lymphocytes was examined by single cell gel electrophoresis.Results The increase of body mass[( 121.00 ± 38.57), ( 120.62 ± 42.80), ( 125.38 ± 48.68)g]and water intake [(36.9 ± 6.2), (37.9 ± 5.8), (39.3 ± 4.2)ml/d]in 0.05,0.15,0.45 mg/L sodium arsenite groups were compared with the control group[( 119.25 ± 47.27)g, (38.4 ± 5.1 )ml/d], and the difference were not significant (F = 0.040,0.828, all P ＞ 0.05). The tail ratios[46.25%(185/400) ,57.00%(228/400),64.00%(256/400)], tail lengths [(32.89 ± 17.18), (58.74 ± 36.28), (77.55 ± 35.73 ) μm]and tail moments [(6.29 ± 3.74), ( 11.20 ± 9.64),(17.30 ± 12.60)μm]in 0.05,0.15,0.45 mg/L sodium arsenite groups were significantly higher than those of the control group[39.25%(157/400), (18.73 ± 15.83),(2.61 ± 1.05)μm, all P ＜ 0.01], and the tail ratios,tail lengths and tail moments in lymphocytes increased with increased doses of arsenic concentration. Conclusions Low doses of arsenic exposure can induce DNA damage in peripheral blood lymphocytes of rats.     

异基因间充质干细胞移植治疗多发性肌炎/皮肌炎的临床研究

目的 探讨异基因间充质干细胞(MSC)移植治疗多发性肌炎/皮肌炎(PM/DM)的临床疗效及安全性.方法 8例难治性PM/皮肌炎患者经静脉输注异基因骨髓或脐带来源MSC,评价患者移植前后血清肌酸激酶(CK)、手工肌力评分(MMT8)等实验室及临床指标,采用配对t检验.结果 异基因MSC移植后随访6～12个月.5例患者移植后1周血清CK值由移植前(1681±430)U/L下降至(886±248)U/L(P＜0.05),移植后2周(474±61)U/L、1个月(293±89)U/L、3个月(202±70)和6个月(175±46)U/L继续下降,与移植前比,差异均有统计学意义(P＜0.05).2例患者在随访9个月时病情复发,血清CK上升.MMT8在移植后1个月67±3、3个月64±10、6个月64±4均显著上升,与移植前45±14比,差异有统计学意义(P＜0.05).所有患者移植后2周口服糖皮质激素(甲泼尼龙)用量较移植前显著减少[(18±6)mg与(34±15)mg,P＜0.05].2例以肺间质病变为主的患者,移植后临床症状缓解、肺部高分辨率CT显示间质性肺炎明显改善.1例以皮肤难治性溃疡为主的皮肌炎患者,移植后溃疡明显愈合.所有患者均无移植相关并发症.结论 异基因MSC移植治疗PM/皮肌炎安全有效,其长期疗效有待进一步观察.

Abstract：

Objective To explore the clinical efficacy of allogenic mesenchymal stem cells transplantation (MSCT) in patients with refractory polymyositis/dermatomyositis (PM/DM). Methods Bone marrow derived mesenchymal stem cells (BM-MSC) or umbilical cord derived mesenchymal stem cells (UC-MSC)were infused intravenously in 8 PM/DM patients. The clinical manifestations and laboratory parameters,including serum creatin in kinase (CK) and manual muscle test 8 (MMT8) score, were compared before and after MSCT. Staistically andlyzed by paired t-test. Results The eight patients were followed up for six to twelve months after MSCT. The level of serum CK decreased from (1681±430) to (886±248) U/L one week after MSCT (P＜0.05) and further decreased at week 2 (474±61) U/L, 1 month (293±89) U/L, 3 month (202±70) U/L and 6 month (175±46) U/L, respectively (all P＜0.05). MMT8 score increased to 1 month [(67±3) vs (45±14), P＜0.05], 3 month [(64±10) vs (45±14), P＜0.05], 6 month [(64±4) vs (45±14),P＜0.05] after MSCT. The dosage of glucocorticoid steroid were tapered in all patients 2 weeks after MSCT [(18±6) mg vs (34±15) mg, P＜0.05]. Clinical symptoms of interstitial pneumonia of both patients were relieved after MSCT, which was confirmed by the result of high resolution CT (HRCT) of the lung.The skin ulcers tended to be recovered after the transplantation in one DM patient. All patients did not develop transplantation related complications. Conclusion Allogenic MSCT is an effective and safe approach for the treatment of refractory PM/DM. However, extensive follow-up study is needed for long-term benefit evaluation.     

英夫利西单抗对类风湿关节炎患者血清抗酒石酸酸性磷酸酶5b的影响

目的 观察英夫利西单抗治疗活动性类风湿关节炎(RA)患者前后血清抗酒石酸酸性磷酸酶5b(TRACP-5b)水平,并分析其与RA患者各项活动性指标及疗效的相关性,比较不同抗RA药物对骨侵蚀的影响并阐明可能的机制.方法 36例RA患者随机分为2组,英夫利西单抗治疗组16例,甲氨蝶呤(MTX)治疗组20例,记录所有患者24周的临床及实验室指标.对比2组间及组内血清TRACP-5b水平的差异,并分析其与RA各项活动性指标及疗效的相关性.计量资料组间比较采用秩和检验、成组设计和配对设计的t检验,计数资料采用x2检验,相关分析采用Spearman、Pearson相关分析.结果 基线X线表现为Ⅰ、Ⅱ、Ⅲ、Ⅳ期的RA患者血清TRACP-5b水平分别为(1.69±0.48)、(2.64±1.13)、(3.34±1.07)、(4.05±0.25)U/L,Ⅲ、Ⅳ期TRACP-5b水平与Ⅰ期比较差异有统计学意义(P＜0.05).治疗24周后,英夫利西单抗治疗组血清TRACP-5b水平为(2.16±1.09)U/L,较MTX治疗组[(3.05±0.93)U/L ]低,差异有统计学意义(P＜0.05);较英夫利西单抗组治疗前血清TRACP-5b水平[(3.07±1.32)U/L]低,差异有统计学意义(P＜0.05).活动性RA血清中TRACP-5b基线水平与病程、健康评价呈正相关(r=0.313,P=0.043;r=0.443,P=0.007).结论 TRACP-5b血清水平随RA关节X分期增加而升高;血清TRACP-5b的治疗变化可能反映了英夫利西单抗对RA骨破坏的抑制作用.治疗24周后,英夫利西单抗治疗组血清TRACP-5b水平较甲氨蝶呤治疗组明显低,提示英夫利西单抗对破骨细胞的抑制作用可能优于MTX.

Abstract：

Objective To detect the serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) in patients with rheumatoid arthritis (RA) before and after infliximab treatment and analyze the relevance between TRACP-5b and activity indexes of RA.The effect of different medicines on bony erosion in RA and its possible mechanism were explored.Methods Patients were divided into two groups:16 patients were treated with inffiximab for 24 weeks (group 1 ),25 patients were treated with MTX for 24 weeks (group 2).The core indicators of RA activity were evaluated.Ranked test,grouped design and matched t test was used to examine the quantity data between groups,while numerate data was analyzed with qui-square test.Correlation between data was tested by Spearmen's and Pearson's tests.RestltsThe levels of TRACP-5b in patients with X-ray stagesⅠ ,Ⅱ ,Ⅲ ,Ⅳ were elevated at the baseline.The levels of TRACP-5b in phase Ⅲ and Ⅳ were [(3.34±1.07) U/L] and[(4.05±0.25) U/L] respectively,higher (P＜0.05) than those in phase Ⅰ[(1.69±0.48) U/L].At week 0,week 12,and week 24,the serum levels of TRACP-5b in group 1 were(3.07±1.32),(2.72±1.18),(2.16±1.09) U/L respectively,while the levels in week 12,and 24 were significantly lower than those of week 0(P＜0.05).A significant decrease of serum TRACP-5b level in group 1[(2.16±1.09 ) U/L]when compared to group two[ (3.05±0.93) U/L] after 24 weeks.TRACP=5b level was positively correlated with the course of disease (r=0.313,P=0.043 ),HAQ(r=0.443,P=0.007).Conclusion Infliximab can reduce TRACP-5b level in RA and inhibit inflammatory bone loss.TRACP-5b can be used to evaluate the efficacy of biological agents in treating RA.     

椎动脉支架置入术后sICAM-1、hs-CRP和TNF-α血清浓度的变化及其临床意义

目的 观察椎动脉支架置入术后血清炎性细胞因子的动态变化并探讨其临床意义.方法 纳入48例椎动脉支架置入术患者,以48例单纯接受脑血管造影的患者作为对照组,在支架置入(血管造影)前以及支架置入后24 h、48 h、3 d、1周和3周时检测血清可溶性细胞间黏附分子-1(soluble intercellular adhension molecule-1,sICAM-1)、高敏C-反应蛋白(high-sensitivity C-reactive protein,hs-CRP)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平.结果 与支架置入前相比,支架置入组支架置入后24 h时血清ks-CRP[(4.85 4±0.53)mg/L对(2.57±0.36)mg/L,P＜0.05]、TNF-α[(2.42±0.34)μg/L对(1.08±0.37)μg/L,P＜0.05]和sICAM-1[(449.43±47.16)μg/L对(269.15±37.46)μg/L,P＜0.05]水平均显著增高.hs-CRP水平在支架置入后48 h时达高峰[(6.24±0.59)mg/L],3周时[(2.51±0.29)mg/L]恢复至支架置入前水平[(2.57±0.36)mg/L];TNF-α水平支架置入后3 d时[(2.30±0.25)μg/L]达高峰,3周时[(1.89±0.13)μg/L]仍维持在较高水平;sICAM-1水平则持续升高至3周时[(296.95±59.72)μg/L].支架置入组支架置入后24 h血清hs-CRP、TNF-α和sICAM-1水平分别显著高于对照组造影后24 h时的(3.25±0.40)mg/L、(1.184±0.19)μg/L和(336.57±50.18)μg/L(P均＜0.05).结论 椎动脉支架置入术后血清hs-CRP、TNF-α和sICAM-1水平显著增高,提示支架置入引起了持续时间较长的炎症反应.

Abstract：

Objective To observe the dynamic changes of serum inflammatory factors after vertebral artery stenting and to investigate its clinical significance. Methods A total of 48 patients treated with vertebral artery stenting were included, and 48 patients only received cerebral angiography were used as a control group. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), high-sensitivity C-reactive protein (hs-CRP) and tumor-necrosis factor-α (TNF-α) were detected before procedure (angiography), at 24 h, 48 h, 3 d, and 1 and 3 weeks after procedure (angiography). Results The serum levels of hs-CRP (4. 85 ± 0. 53 mg/L vs. 2. 57 ±0. 36 mg/L,P＜0. 05), TNF-α (2.42 ±0. 34 μg/L vs. 1. 08 ±0. 37 μg/L,P ＜0. 05) and sICAM-1 (449.43 ± 47. 16 μg/L vs. 269. 15 ± 37. 46 μg/L, P ＜ 0. 05) at 24 hours after procedure in the stenting group were significantly elevated compared with those before procedure. The Hs-CRP level (6.24 ± 0.59 mg/L) reached the peak at 48 hours after procedure. At week 3 (2. 51 ±0.29 mg/L), it returned to the level before procedure (2. 57 ±0. 36 mg/L); TNF-α level reached the peak at day 3 (2.30 ± 0.25 μg/L), and it remained higher level at week 3 (1. 89 ±0. 13 μg/L); the sICAM-1 level continued to rise at week 3 (296. 95 ± 59. 72 μg/L). The serum hs-CRP, TNF-α and sICAM-1 levels at 24 hours after procedure in the stenting group were significantly higher than those (3. 25 ±0.40 mg/L、J. 18 ±0. 19 μg/L and 336. 57 ± 50. 18μg/L) in the control group (all P＜0.05). Conclusions The serum hs-CRP, TNF-α, sICAM-1 levels were significantly elevated after vertebral artery stenting. It was suggested that the stenting caused a longer duration of inflammatory response.     

血浆甘露聚糖结合凝集素与类风湿关节炎肾损害的相关性研究

目的 检测类风湿关节炎(RA)相关性肾损害患者甘露聚糖结合凝集素(MBL)的血浆水平,探讨MBL在RA相关肾损害中可能的作用机制.方法 用酶联免疫吸附试验(ELISA)法检测19例RA相关肾损害患者、49例RA不伴肾损害患者及40名健康对照者的血浆MBL水平,并收集RA患者临床资料及相关实验室检查资料进行对比分析.采用x2检验、t检验和Spearman相关分析进行统计学处理.结果 较无肾损害组比,RA相关肾损害组患者肿胀压痛关节数增多[(15±9)和(9±11)个],晨僵时间延长[(2.9±1.3)和(2.3±1.6)h],其他(除肾脏)关节外伴随症状发生率明显升高[(42.1%和16.3%),P＜0.01或P＜0.05];但二组间RA病程、关节畸形的发生率差异无统计学意义(P＞0.05);RA相关肾损害组血小板(PLT)[(376±155)×109/L和(304±121)×109/L]、循环免疫复合物(CIC)[(4.3±3.0)和(2.9±3.3)g/L]、红细胞沉降率(ESR)[(79±46)和(53±31)mm/1 h]、类风湿因子(RF)[(77±42)和(52±49)U/ml]、C反应蛋白(CRP)[(32±28)和(23±18)mg/L]、免疫球蛋白IgG[(11.7±2.6)和(8.4±2.4)g/L]、补体C3[(1.18±0.53)和(0.94±0.21)g/L]高于RA无肾损害组(P＜0.01或P＜0.05),血浆白蛋白(Alb)[(26±13)比(30±9)g/L]低于无肾损害组(P＜0.05);二组RA患者血浆MBL水平均较对照组血浆MBL水平[(3.1±0.5)mg/L]显著下降(P＜0.01),RA相关肾损害组MBL水平[(1.7±1.2)mg/L]较无肾损害组MBL水平[(1.4±1.3)mg/L]升高(P＜0.05);RA相关肾损害组MBL与IgG、C3、CRP、尿蛋白定量(24 h)呈正相关(r分别为0.6,0.6,0.47,0.57;P＜0.05).结论 RA相关肾损害与免疫复合物相关;RA相关肾损害患者血浆MBL水平是升高的,血浆中高水平MBL可能是RA相关肾损害的发病机制之一.

Abstract：

Objective To detect the serum level of mannose binding lectin (MBL) in patients with renal injury induced by rheumatoid arthritis (RA), and to investigate the role of MBL in the pathogenesis of renal injury in RA. Methods ELISA was used to measure the serum MBL level of 19 RA patients with renal injury, 49 RA patients without renal injury and 40 healthy individuals. The clinical features and laboratory markers were compared and analyzed by chi-square test, two independent samples t-test and Spearman's correlation analysis. Results Compared with RA patients without renal injury, the number of tender and swollen joints [(15±9) vs (9±11)], duration of morning stiffness [(2.9±1.3) vs (2.3±1.6) h] and extraarticular manifestations (42.1％ vs 16.3％) in RA patients with renal injury were significantly higher (P＜0.05or P＜0.01). There was no significant difference between the two groups in RA disease duration and jointdeformity(P＞0.05). In patients with renal injury, the level of platelet count [(376±155)×109/L vs (304±121)×109/L], CIC[(4.3±3.0) vs (2.9±3.3) g/L], ESR[(79±46) vs (53±31) mm/1 h], RF[(77±42) vs (52±49)U/ml], CRP[(32±28)vs (23±18)mg/L], IgG[(11.7±2.6)vs (8.4±2.4)g/L], C3[(1.18±0.53)vs (0.94±0.21) g/L] were higher than those in RA patients without renal injury (P＜0.01 or P＜0.05); the level of Alb [(26±13) vs (30±9) g/L] was lower than that in RA patients without renal injury (P＜0.05). The level of serum MBL in the two groups of RA patients was significantly lower than that in the healthy group [(3.1±0.5)mg/L](P＜0.01), and the level of serum MBL in RA patients with renal injury [(1.7±1.2) mg/L] was higher than that in RA patients without renal injury [(1.4±1.3) mg/L](P＜0.05). The level of serum MBL in RA patients with renal injury showed a positive correlation with IgG, C3, CRP and 24 h urine protein level (r=0.6, 0.6, 0.47, 0.57; P＜0.05). Conclusion Renal injury in RA patients is immune complex dependent. The serum level of MBL is higher in patients with renal injury, therefore, high-concentration MBL may be one of a potential causes of renal injury in RA patients.     

氟致体外培养人脐静脉血管内皮细胞损伤的实验观察

目的 观察不同剂量的氟对体外培养人脐静脉血管内皮细胞(HUVEC)的影响.方法 在HUVEC培养液中加入不同剂量的氟化钠(NaF),分别为0(对照)100、400、700、1000、2000 μmol/L,每组设6个复孔,连续培养48 h,收集细胞培养液与细胞.瑞氏-吉姆萨染色观察细胞形态,吖啶橙荧光染色测定细胞凋亡,四唑氮蓝(MT T)比色法检测细胞活性;分光光度法检测细胞培养液中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)水平及诱导型一氧化氮合酶(iNOS)、内皮型一氧化氮合酶(eNOS)活性;RT-PCR法检测细胞iNOS mRNA和eNOS mRNA表达水平;双抗体夹心ELISA法检测细胞培养液中细胞黏附因子(ICAM-1)、血管黏附因子(VCAM-1)水平.结果 随染氟剂量增加,HUVEC细胞数量减少,结构改变;400～2000μmol/L NaF组SOD活性[(6.627±0.213)、(6.668±0.152)、(5.935±0.122)、(4.755±0.182)kU/L]较对照组[(7.457±0.398)kU/L]降低(P＜0.05或＜0.01),GSH-Px活性[(481.284±43.785)、(492.223±16.474)、(382.762±25.167)、(293.687±24.881)kU/L]较对照组[(585.078±47.323)kU/L]降低(P＜0.05或＜0.01),MDA水平[(0.609±0.011)、(0.646±0.016)、(0.852±0.013)、(1.188±0.045)nmol/L]较对照组[(0.512±0.027)nmol/L]升高(P＜0.05或＜0.01);iNOS活性[(3.604±0.115)、(3.615±0.075)、(3.848±0.103)、(4.275±0.079)kU/L]较对照组[(2.798±0.136)kU/L]增强(P均＜0.01),iNOS mRNA表达增强,eNOS活性[(5.539±0.079)、(5.503±0.064)、(5.226±0.142)、(4.809±0.107)kU/L]较对照组[(5.996±0.155)kU/L]减弱(P＜0.05或＜0.01),eNOSmRNA表达减弱;ICAM-1水平[(0.852±0.102)、(0.886±0.061)、(0.961±0.158)、(1.418±0.167)μg/L]较对照组[(0.687±0.046)μg/L]升高(P＜0.05或＜0.01),VCAM-1水平[(2.719±0.197)、(2.946±0.167)、(3.173±0.225)、(3.613±0.153)μg/L]较对照组[(2.375±0.067)μg/L]升高(P均＜0.01).结论 高剂量氟降低抗氧化酶活性,使一氧化氮代谢紊乱,细胞因子异常表达,以此抑制血管内皮细胞生长、结构改变并致细胞凋亡,为高氟致血管内皮损伤的重要因素.

Abstract：

Objective To study the effect of different concentrations of fluoride on cultured human umbilical vein vascular endothelial cells(HUVEC). Methods Different doses of sodium fluoride (NaF) were added to HUVEC culture medium, fluoride concentrations were 0(control), 100,400,700,1000,2000 μmol/L, respectively,6 re-set hole in each group. After continuous culture for 48 h, cells and culture medium were collected. Cell morphology was studied by Wright-Giemsa staining; cells apoptosis was determined by acridine orange fluorescence staining; cell activity was measured by methyl thiazolyl tetrazolium (MTT) assay; superoxide dismutase (SOD),glutathione peroxidase(GSH-Px) activity, malonaldehyde(MDA) content, induced nitricoxide synthase(iNOS), and endothelia nitricoxide synthase(eNOS) activity in cell culture medium were determined by spectrophotometry; cell iNOS mRNA and eNOS mRNA expression were detected by RT-PCR; intercellular adhesion molecule-1 (ICAM-1)and vascular cell adhesion molecule-1 (VCAM-1) levels were detected by double antibody sandwich ELISA method.Results With increased dose of fluoride, HUVEC cells decreased, the structure changed. In 400 - 2000 μmol/L group, the SOD activity[(6.627 ± 0.213), (6.668 ± 0.152), (5.935 ± 0.122), (4.755 ± 0.182)kU/L] was lower than those of the control group[(7.457 ± 0.398)kU/L, P ＜ 0.05 or ＜ 0.01], GSH-Px activity[(481.284 ± 43.785),(492.223 ± 16.474), (382.762 ± 25.167), (293.687 ± 24.881 )kU/L] was also lower than those of the control group [(585.078 ± 47.323)kU/L, P ＜ 0.05 or ＜ 0.01], MDA level[(0.609 ± 0.011 ), (0.646 ± 0.016), (0.852 ± 0.013),(1.188 ± 0.045)nmol/L] was higher than those of the control group[(0.512 ± 0.027)nmol/L, P ＜ 0.05 or ＜ 0.01];iNOS activity[(3.604 ± 0.115), (3.615 ± 0.075), (3.848 ± 0.103), (4.275 ± 0.079)kU/L] also was higher than those of the control group[(2.798 ± 0. 136)kU/L, all P ＜ 0.01], iNOS mRNA expression increased, eNOS activity [(5.539 ± 0.079), (5.503 ± 0.064), (5.226 ± 0.142), (4.809 ± 0. 107)kU/L] decreased compared to those of control group[(5.996 ± 0.155)kU/L, P ＜ 0.05 or ＜ 0.01], eNOS mRNA expression decreased; ICAM-1 levels [(0.852 ± 0. 102), (0.886 ± 0.061 ), (0.961 ± 0.158), (1.418 ± 0. 167)μg/L] increased compared to those of the control group[(0.687 ± 0.046)μg/L, P ＜ 0.05 or ＜ 0.01], VCAM-1 levels[(2.719 ± 0.197), (2.946 ± 0.167),(3.173 ± 0.225 ), (3.613 ± 0. 153 ) μg/L] was higher than those of the control group [(2.375 ± 0.067 ) μg/L, all P ＜0.01]. Conclusions High concentrations of fluoride reduce the activity of antioxidant enzymes, which leads to metabolic disorders of nitric oxide and abnormal cytokines expression, thereby inhibiting vascular endothelial cell growth, structural change and induced apoptosis. This is an important factor in high fluoride-induced vascular endothelial injury.     

血管性血友病因子和ADAMTS-13水平与急诊冠状动脉支架置入术后冠状动脉血流的关系

目的 探讨急性ST段抬高型心肌梗死(STEMI)患者血浆血管性血友病因子(vWF)和其裂解酶ADAMTS-13水平与急诊冠状动脉支架置入术后冠状动脉心肌梗死溶栓试验(TIMI)血流的关系.方法 根据支架释放后即刻造影显示的TIMI血流情况,将2007年9月至2009年12月期间在我院行急诊冠状动脉支架置入术的STEMI患者分为TIMI≤2级组(最终入选43例)和TIMI 3级组(最终入选43例),并选择同期冠状动脉造影正常的胸闷、胸痛患者作为阴性对照组(43例).采用双抗体夹心酶联免疫吸附法(ELISA)分别在入院即刻、冠状动脉介入术开始即刻以及介入术后1周检测患者外周血vWF和ADAMTS-13水平.结果 在不同时间TIMI≤2级组和TIMI 3级组血浆vWF水平均显著高于阴性对照组(均P＜0.05).TIMI≤2级组血浆vWF水平在不同时间均显著高于T1MI 3级组[分别为入院即刻(6721.83±1380.58)U/L比(4786.12±2362.01)U/L,P＜0.05;介入术开始即刻(5744.65±1240.71)U/L比(3011.33±2270.40)U/L,P＜0.05;介入术后1周(2001.48±931.70)U/L比(1365.17±724.12)U/L,P＜0.05].3组患者入院即刻和介入术开始即刻血浆ADAMTS-13水平差异无统计学意义.术后1周TIMI ≤2级组ADAMTS-13水平明显高于TIMI 3级组[(406.93±101.44)mg/L比(270.34±115.12)mg/L,P＜0.05].logistic回归分析表明,入院即刻vWF水平(OR:1.917,P＜0.01)和介入术开始即刻vWF水平(OR:2.016,P＜0.01)均是影响支架术后冠状动脉TIMI血流的危险因素.结论 STEMI患者急诊支架术后冠状动脉TIMI血流状况与患者术前血浆vWF水平有关,vWF与ADAMTS-13的失衡可能是急诊支架置入术后冠状动脉血流缓慢的原因之一.

Abstract：

Objective To investigate the relationship between post-stenting coronary thrombolysis in myocardial infarction (TIMI) flow and plasma von Willebrand factor (vWF) and its cleaving protease(ADAMTS-13) levels in patients with ST segment elevation myocardial infarction (STEMI). Methods STEMI patients who underwent primary percutaneous coronary intervention ( PCI ) and stenting between September, 2007 and December, 2009 were enrolled. According to the post-stenting TIMI flow, patients were divided to TIMI≤2 group (n =43) and TIMI 3 group (n =43). Patients with chest pain or dyspnea and normal coronary angiographic results served as control group ( n = 43 ). The levels of vWF and ADAMTS-13 were measured by ELISA at three time points: immediatly after admission, beginning of PCI and 1 week after PCI. Results Levels of vWF in STEMI patients at all 3 time points were significantly higher than in control patients, and the level of vWF was significantly higher in TIMI ≤2 group than in TIMI 3 group [at admission: (6721.83 ± 1380.58) U/L vs. (4786. 12 ±2362.01) U/L, P ＜0.05; at the beginning of PCI: (5744.65 ±1240. 71) U/L vs. (3011.33 ±2270.40) U/L, P＜0. 05 and at 1 week after PCI: (2001.48 ± 931.70) U/L vs. ( 1365. 17 ± 724. 12 ) U/L, P ＜ 0. 05]. ADAMTS-13 levels were similar among groups at admission and at beginning of PCI, however, the level of ADAMTS-13 at 1 week after PCI was significantly higher in TIMI≤2 group than that in TIMI 3 group [(406. 93 ± 101.44 )mg/L vs. ( 270. 34 ± 115.12) mg/L, P ＜0. 001]. Logistic regression analysis showed that both vWF at admission(OR=1.917, P＜0.01) and vWF at the beginning of PCI (OR=2.016, P＜0. 01) were risk factors of TIMI≤2. Conclusion Increased vWF during peri-PCI periods was associated with post-stenting coronary TIMI ≤2 after primary PCI in STEMI patients, and the imbalance between vWF and ADAMTS-13 may thus play an important role in the development of slow flow post PCL     

短期铁缺乏对大鼠甲状腺功能的影响

目的 研究短期铁缺乏对大鼠甲状腺功能的影响,并探讨其机制,为碘缺乏病的防治工作提供新的线索和思路.方法 选择健康SPF/VAF级初断乳SD雄性大鼠22只,按体质量随机分为对照组(饲料含铁量为65 mg/kg)和铁缺乏组(饲料含铁量为15 mg/kg),每组11只.喂养4周后,测定大鼠体质量和甲状腺质量,并计算甲状腺相对质量.取大鼠全血并分离血清,采用生化法检测血红蛋白、血清铁水平和总铁结合力;化学发光法检测血清游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)和促甲状腺激素(TSH)水平.甲状腺常规固定包埋切片后,免疫组化染色观察甲状腺过氧化物酶(TPO)蛋白表达情况.结果 铁缺乏组大鼠体质量[(214.3±18.1)g]比对照组[(243.8±16.4)g]减轻(t=4.002,P＜0.01),甲状腺绝对质量[(11.9±1.6)mg]比对照组[(13.4±1.3)mg]降低(t=2.369,P＜0.01),但甲状腺相对质量[(0.055±0.004)g/kg]与对照组[(0.055±0.006)g/kg]比较未见明显变化(t=0.162,P＞0.05).铁缺乏组大鼠血红蛋白水平[(100.4±8.9)g/L]和血清铁水平[(7.0±0.8)μmol/L]比对照组[(146.5±16.3)g/L、(26.1±5.1)μmol/L]降低(t值分别为8.233、12.277,P均＜0.01),总铁结合力[(124.8±6.3)μmol/L]比对照组[(74.0±4.6)μmol/L]升高(t=21.531,P＜0.01).铁缺乏组大鼠血清FT3、FT4和FT3/FT4[(4.71±0.53)、(29.69±2.63)pmol/L、0.16±0.02]均较对照组[(5.69±0.61)、(31.98±2.49)pmol/L、0.18±0.01]降低(t值分别为4.044、2.096、3.255,P＜0.01或＜0.05).铁缺乏组大鼠TPO蛋白表达强度较对照组减弱.结论 铁缺乏可导致甲状腺功能低下,可能与铁缺乏状态下TPO活性降低有关,碘铁联合补充可能会改善铁缺乏地区碘缺乏病防治的效果.

Abstract：

Objective To explore the effect of short-term iron deficiency on thyroid function of rat and its mechanism, and to provide new clues and ideas for prevention and control of iodine deficiency disorders. Methods Twenty-two healthy SPF/VAF level weaning male SD rats were randomly divided into control group(iron content in diet was 65 mg/kg) and iron deficiency group(iron content in diet was 15 mg/kg) by body weight, and 11 in each group respectively. After 4 weeks feeding, body weight and thyroid glands weight were measured, and the relative weight of thyroid gland was calculated. Rat whole blood was collected and serum was separated. Hemoglobin, serum iron levels and total iron binding capacity were tested using biochemical assay;serum free iodine thyroid three original acid (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels were detected by chemiluminescence;after thyroid were fixed in formalin, embedded with paraffin and sectioned regularly, and immunohistochemical stained, the protein expression of thyroid peroxidase(TPO) was observed. Results Compared with control group [(243.8 ± 16.4)g], iron deficiency group of animals had less body weight[(214.3 ± 18.1 )g, t = 4.002, P ＜ 0.01];there was a lower absolute thyroid weight in iron deficiency group[(11.9 ± 1.6)mg]than in control group[(13.4 ±1.3)mg, t = 2.369, P ＜ 0.01], but no significant changes of the relative weight of thyroid gland between the two groups[(0.055 ± 0.004),(0.055 ± 0.006)g/kg, t = 0.162, P ＞ 0.05]. Hemoglobin and serum iron in iron deficiency group were ( 100.4 ± 8.9)g/L and (7.0 ± 0.8)μmol/L, which were less than that in control group[( 146.5 ±16.3)g/L, (26.1 ± 5.1 )μmol/L, t = 8.233,12.277, all P ＜ 0.01]. Total iron binding capacity in control group was (74.0 ± 4.6)μ mol/L and that in iron deficiency group[(124.8 ± 6.3)μmol/L], and the difference was significant (t = 21.531, P＜ 0.01). At the same time, their serum hormones FT3, FT4 and FT3/FT4[(4.71 ± 0.53), (29.69 ±2.63)pmol/L, 0.16 ± 0.02]were lower than that in control group[(5.69 ± 0.61),(31.98 ± 2.49)pmol/L, 0.18 ±0.01, t = 4.044,2.096,3.255, P ＜ 0.01 or ＜ 0.05]. The expression of TPO protein decreased in iron deficiency group than in control group. Conclusions Iron deficiency reduces thyroid function, which perhaps is due to the reduction of TPO activity. Combined supplementation of iodine and iron will possibly improve the prevention effect on iodine deficiency disorder in iron deficiency areas.     

曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响

目的 探讨曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响。方法 随机将65只C57BL/6小鼠分为对照组、模型组、小、中、大剂量曲美他嗪处理组和还原型谷胱甘肽处理组,除模型组15只外,其他组均为10只。采用D-氨基半乳糖联合脂多糖腹腔注射建立急性肝衰竭模型。取肝组织匀浆检测丙二醛(MDA)和过氧化物酶(CAT)含量,采用RT-PCR法和Western blot法分别检测肝组织还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶( NOX2/4) mRNA水平和蛋白表达。结果 模型组血清ALT、AST和肝匀浆MDA水平分别为(121.4±3.7)U/L、(208.9±27.4)U/L和(51.0±20.5)nmol/mg,均显著高于对照组【分别为(35.3±3.2)U/L、(49.9±4.4)U/L和(14.1±5.2)nmol/mg,P＜0.05】,而模型组肝匀浆CAT水平为(51.7±16.8)U/mg,显著低于对照组【(110.2±33.7)U/mg,P＜0.05】;模型组NOX2/4 mRNA和蛋白相对水平分别为(8.2±2.0)/(1.2±0.1)和(2.6±0.1)/(1.3±0.1),均显著高于对照组【分别为(1.0±0.2)/(0.5±0.1)和(1.0±0.1)/(0.4±0.1),P＜0.05】,中、大剂量曲美他嗪处理组血清ALT和AST及肝匀浆MDA水平分别为(86.4±1.00)U/L、(154.0±6.2)U/L和(22.5±1.9)nmol/mg及(81.1±1.5)U/L、(134.7±5.3)U/L和(20.1±3.7)nmol/mg,均显著低于模型组【分别为(121.4±3.7)U/L、(208.9±27.4)U/L和(51.0±20.5)nmol/mg,P＜0.05】,肝匀浆CAT水平分别为(99.4±15.5)和(102.3±15.5),均显著高于模型组【(51.6±16.8),P＜0.05】;肝组织NOX2/4 mRNA及蛋白相对表达量分别为(5.6±0.2)/(0.7±0.0)和(5.2±1.4/0.6±0.1)及(1.7±0.2)/(0.7±0.2)和(1.5±0.1)/(0.6±0.2),均显著低于模型组【(8.2±2.0)/(1.2±0.1)和(2.6±0.1)/(1.3±0.1),P＜0.05】。结论 曲美他嗪可能通过下调肝组织NOX2/4表达减轻氧化应激损伤,改善D-Galn/LPS诱导的急性肝衰竭小鼠肝损伤。     

血小板衍生生长因子和Ⅰ型胶原在饮水砷暴露小鼠肝组织中的表达

目的 探讨血小板衍生生长因子(PDGF)和Ⅰ型胶原(Col-Ⅰ)在饮水砷暴露小鼠肝组织中的表达及其意义.方法 50只昆明种雄性小鼠被分成对照组、iAs3+组、iAs5+组.分别饮用自来水,亚砷酸钠溶液(NaAsO2,含砷离子300 mg/L),砷酸钠溶液(Na2HAsO4·7H2O,含砷离子300 mg/L).10个月后处死小鼠,使用全自动生化分析仪检查肝功能,包括血清丙氨酸转氨酶(ALT)、天冬氨酸转氧酶(AST)、球蛋白(GLB);Masson染色肝组织,检测单位视场内的纤维面积;免疫组化(SABC)法检测肝组织中PDGF和Col-Ⅰ的表达.结果 ①对照组、iAs3+组、iAs5+组,血清ALT水平分别为(36.67±3.51)、(61.46±13.85)、(43.31±4.21)U/L,组间比较差异有统计学意义(F=6.56,P<0.05),iAs3+组明显高于对照组(P<0.05);血清AST水平分别为(135.00±20.42)、(510.86±59.01)、(258.93±22.40)U/L,组间比较差异有统计学意义(F=83.33,P<0.05),iAs3+、iAs5+组均明显高于对照组(P<0.05),iA3+组明显高于iAs5+组(P<0.05);血清GLB水平分别为(20.86±0.61)、(26.94±3.73)、(24.59±5.27)g/L,组间比较差异无统计学意义(F=2.80,P>0.05).②光镜下染砷组小鼠肝组织出现明显的细胞变性、坏死、再生,汇管区炎细胞浸润,纤维增生.对照组(0.069±0.013)、iAs3+组(0.192±0.108)和iAs5+组(0.143±0.122)单位视场内的纤维面积组间比较,差异有统计学意义(F=1.91,P<0.05),iAs3+组明显高于对照组(P<0.05).③对照组、iAs3+组、iAs5+组PDGF、Col-Ⅰ光密度值分别为202.788±7.462、174.382±7.706、177.644±7.811,200.11±7.46、176.47±10.20、177.38±7.95,组间比较差异均有统计学意义(F值分别为102.91、78.51,P均<0.05),与对照组比较,iAg3+、iAs5+组PDGF、Col-Ⅰ光密度值明显降低(P<0.05).表明肝组织内PDGF、Col-Ⅰ表达明显增多.且PDGF在汇管区、间隔细胞、窦旁细胞内均有表达,而Col-Ⅰ表达广泛分布于血管及胆管周围,并自门管区向肝实质内延伸形成纤维间隔.结论 长期饮水砷暴露,可导致慢性肝脏损伤、肝纤维化形成.PDGF、Col-Ⅰ在砷敛小鼠肝纤维化形成中起重要作用.     

异甘草酸镁与复方甘草酸单胺治疗药物性肝损伤患者疗效比较研究*

目的 分析比较异甘草酸镁与复方甘草酸单胺治疗药物性肝损伤(DILI)患者的疗效。方法 2018年1月～2020年1月我院收治的DILI患者102例,随机分为观察组51例和对照组51例,分别给予异甘草酸镁或复方甘草酸单胺静脉滴注治疗14～28 d。采用放射免疫法检测层粘连蛋白(LN)、透明质酸酶(HA)、III型前胶原(PC-III)和IV型胶原(IV-Col)水平,采用ELISA法检测超氧化物歧化酶(SOD)、一氧化氮(NO)、白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。结果 治疗后,观察组血清ALT和AST水平分别为(42.7±12.5)U/L和(38.2±9.4)U/L,显著低于对照组【分别为(64.5±21.9)U/L和(55.6±15.2)U/L, P＜0.05】;血清HA、PC-III和IV-Col水平分别为(138.2±21.5)mg/L、(85.6±17.4)μg/L和(141.5±16.4)μg/L,显著低于对照组【分别为(182.1±23.9)mg/L、(123.8±19.4)μg/L和(175.4±18.7)μg/L,P＜0.05】;血清SOD和NO水平分别为(90.3±10.1)U/L和(79.8±9.3)μmol/L,显著高于对照组【分别为(74.9±8.6)U/L和(54.0±7.9)μmol/L,P＜0.05】,而血清IL-6和TNF-α水平分别为(11.2±2.5)pg/mL和(26.4±3.6)ng/L,显著低于对照组【分别为(16.8±2.7)pg/mL和(41.3±5.9)ng/L,P＜0.05】。结论 应用异甘草酸镁治疗DILI患者临床疗效优于复方甘草酸单胺,可有效改善血生化指标和肝纤维化指标,可能与减轻了机体氧化应激和炎症反应有关。     

联合降压对中青年女性高血压病患者性功能的影响

目的 探讨以非洛地平为基础的联合降压方案在降压达标的基础上对中青年女性高血压病患者性功能的影响.方法 研究采用前瞻性、随机、平行、对照、开放、固定治疗的设计方案.选择2008-2009年在兰州大学第二医院就诊的中青年(年龄18～60岁)女性1～2级高血压病患者99例,随机分2组:非洛地平缓释片5 mg/d+厄贝沙坦片150 mg/d(F+I组,n=49),非洛地平缓释片5 mg/d+琥珀酸美托洛尔片47.5 mg/d(F+M组,n=50).以美国女性性功能指数量表(FSFI)进行问卷调查并检测血清雌二醇和总睾酮的含量,随访24周.FSFI总分以小于25.5定义为性功能障碍,以血压＜140/90 mm Hg(1 mm Hg=0.133 kPa)为达标.结果 F+I组与F+M组治疗第4、8、12周和第24周血压达标率分别为42.9%比62.0%、89.8%比90.0%、93.9%比94.0%和98.0%比96.0%,两组之间比较差异均无统计学意义(均P＞0.05).绝经前与绝经后患者在F+I组治疗后性欲指数和性唤起功能指数均升高(P分别＜0.05或＜0.01),雌二醇水平升高[绝经前:(50.3±37.4)pg/L比(54.4±10.8)pg/L,绝经后:(18.4±2.9)pg/L比(20.2±3.1)pg/L,P分别＜0.05或＜0.01],睾酮水平下降[绝经前:(722.8±277.1)ng/L比(650.0±156.0)ng/L,绝经后:(841.2±279.3)ng/L比(761.9±197.8)ng/L,P分别＜0.05或＜0.01];在F+M组治疗后性欲指数和阴道湿润度指数均降低(均P＜0.01),雌二醇水平降低[绝经前:(57.4±9.7)pg/L比(51.1±12.1)pg/L,绝经后:(19.8±2.3)pg/L比(17.8±3.3)pg/L,均P＜0.01],睾酮水平升高[绝经前:(775.6±217.8)ng/L比(886.0±186.4)ng/L,绝经后:(812.5±311.3)ng/L比(914.4±300.2)ng/L,均P＜0.01].高血压组FSFI总分与年龄和收缩压水平均呈负相关(均P＜0.01).结论 非洛地平缓释片与厄贝沙坦片或琥珀酸美托洛尔片联合降压达标率相同.前者可以在一定程度改善女性高血压病患者性功能.     

氟中毒大鼠骨组织中内质网应激实验研究

目的 观察内质网应激在氟中毒大鼠骨组织中的变化,探索内质网应激在氟骨症发病机制中的可能作用.方法 48只Wistar大鼠,按体质量分成4组,每组12只.对照组和低钙组分别饲以常食饲料(含钙量为0.790%)和自制低钙饲料(含钙量为0.063%),饮用自来水(含NaF＜1 mg/L);高氟组和低钙高氟组分别饲以常食饲料和自制低钙饲料,饮用加氟(NaF,221 mg/L)自来水.实验期间动物自由进食、进水,每周测体质量1次.实验期3个月.生化方法检测大鼠血清氧化应激酶、尿酸(URIC)和碱性磷酸酶(ALP)活性.抽提大鼠一侧股骨骨干的总RNA,利用RT-PCR技术分析内质网应激相关基因BIP、Xbp1、CHOP和PDI的表达水平.结果 低钙高氟组血清丙二醛(MDA)水平高于对照组[(14.74±3.11)μmol/L比(10.15±1.96)μmol/L,P＜0.05];高氟组血清谷胱甘肽过氧化物酶(GPx)的活性高于对照组[(3.87±0.41)×103 U/L比(2.85±0.55)×103U/L,P＜0.05];高氟组和低钙高氟组的尿酸(URIC)分别低于对照组和低钙组[(73.95±9.52)μmol/L比(110.43±25.48)μmol/L,(54.32±22.09)μmol/L比(101.71±17.01)μmol/L/L,P＜0.05].低钙高氟组大鼠的ALP活性高于对照组[(24.77±4.57)×103 U/L比(12.91±3.97)×103 U/L,P＜0.01)].低钙组和低钙高氟组BIP/GAPDH的表达高于对照组(1.38±0.24、1.35±0.12比1.14±0.06,P＜0.05).低钙高氟组的Xbp1/GAPDH的表达高于对照组和低钙组(1.48±0.20比1.02±0.25、1.07±0.25,P＜0.01);低钙高氟组的CHOP/GAPDH的表达高于对照组(0.84±0.18比0.52±0.07,P＜0.05).结论 氟中毒大鼠机体内氧化应激态和骨形成有明显的增强,并伴有骨组织细胞的内质网应激.说明内质网应激与氧化应激很可能都参与了氟骨症的发病机制.     

不同组合人工肝支持系统治疗乙型肝炎病毒相关早、中期慢加急性肝衰竭患者的疗效及对炎症指标的影响

目的 比较不同组合人工肝支持系统治疗乙型肝炎病毒相关早、中期慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者的疗效及对炎症指标的影响.方法 纳入2019年1月至2020年1月在成都市公共卫生临床医疗中心治疗的早、中期...     

恩替卡韦联合甘草酸二铵治疗慢性乙型肝炎患者效果研究*

目的 探讨应用恩替卡韦联合甘草酸二铵治疗慢性乙型肝炎(CHB)患者的短期效果和血清细胞因子水平变化。方法 2019年1月～2020年2月我院收治的98例CHB患者,被随机分为对照组49例和观察组49例,两组均接受恩替卡韦治疗,在此基础上,给予观察组加用甘草酸二铵口服,两组均持续治疗观察12个月。采用放射免疫法检测血清透明质酸 (HA) 、层粘连蛋白(LN) 、IV型胶原( CIV) 、III型前胶原(PIIIP) 水平,采用ELISA法检测血清白介素 2(IL- 2)、白介素4(IL- 4)、白介素 10(IL- 10)和肿瘤坏死因子α(TNF-α)水平,使用流式细胞仪检测外周血 T 细胞亚群。结果 在治疗12个月末,观察组血清ALT复常率为87.8%,显著高于对照组的71.4%(P＜0.05);观察组血清ALT和AST水平分别为(32.3±6.9)U/L和(38.3±4.7)U/L,显著低于对照组【分别为(47.5±7.6)U/L和(52.9±5.1)U/L,P＜0.05】;观察组血清HA和PⅢP水平分别为(90.6±9.5)ng/mL和(141.6±32.6)ng/mL,显著低于对照组【分别为(126.8±14.6)ng/mL和(168.2±29.9)ng/mL,P＜0.05】;观察组血清IL-4和TNF-α水平分别为(48.8±7.9)ng/L和(11.3±1.9)ng/L,显著低于对照组【分别为(62.6±8.8)ng/L和(18.5±1.7)ng/L,P＜0.05】,而血清IL-10水平为(19.2±2.5)ng/L,显著高于对照组【(12.7±3.4)ng/L,P＜0.05】;观察组外周血CD4⁺细胞百分比和CD4⁺/CD8⁺细胞比值分别为(43.5±5.5)%和(1.6±0.2),显著高于对照组【分别为(38.4±4.7)%和(1.4±0.4),P＜0.05】。结论 应用恩替卡韦联合甘草酸二铵治疗CHB患者可有效改善患者肝功能,抑制肝纤维化进程,控制体内炎症反应,改善免疫功能紊乱。