大蒜油对正己烷在小鼠体内代谢成2,5.己二酮的影响

目的 探讨大蒜油对正己烷(n-hexane)在小鼠体内代谢成2,5.己二酮(2,5.hexanedione,2,5-HD)的影响.方法 取健康成年昆明种小鼠,随机分为正己烷染毒组和大蒜油干预组,分别灌胃给予正己烷和大蒜油,染毒结束后取血,分离血清经乙酸乙酯萃取后气相色谱法测定血清中2,5-HD含量.结果 (1)一次性给予4000 mg/kg正己烷后,小鼠血清中2,5-HD含量随时间延长而增加,10 h后达峰值,20 h后几乎不能检出;(2)对照组小鼠血清中未检出2,5-HD;随着正己烷染毒量的增加,小鼠血清中2,5-HD含量明显增加,2000、4000和6000 mg/kg组染毒8 h后小鼠血清2,5-HD含量分别为8.04、16.68和22.38μg/ml,呈明显的剂量一效应关系;(3)不同周龄小鼠给予正己烷8 h后血清中2,5-HD含量有明显差异,5周龄组(22.83;μg/ml)分别大于4周(19.59μg/ml)和6周龄组(16.42μg/ml),差异有统计学意义(P<0.05);(4)不同性别小鼠给予同剂量正己烷后,雌性小鼠血清中2,5-HD含量(13.22 t,g/na)高于雄鼠(10.34μg/ml),差异有统计学意义P<0.05;(5)正己烷染毒前后2 h分别给予80 mg/kg大蒜油,血清中2,5-HD含量与单纯染毒组相比均明显降低,差异有统计学意义(P<0.05),但染毒前给药组较染毒后给药组更低,但差异无统计学意义(P>0.05);染毒前2 h给予不同剂量大蒜油,10、20、40、80 mg/kg大蒜油+3 000 mg/kS正已烷组小鼠血清2,5-HD含量比染毒组分别降低16.2%、20.8%、22.8%和32.1%,差异有统计学意义(P<0.05,P<0.01),呈明显的剂量一效应关系.结论 在雌性小鼠血清中正己烷的代谢产物2,5-HD高于雄性;5周龄小鼠血清2,5-HD含量较4周和6周龄小鼠高;正己烷染毒前后给予大蒜油可明显减少2,5-HD的生成.     

正已烷对人体血清中髓鞘碱性蛋白的影响

目的 了解正已烷接触对人体血清中髓鞘碱性蛋白(MBP)的影响.方法 选取正已烷接触1年以上的工人269名作为接触组,同时选取未接触正已烷的工人104名作为对照组,测定工人尿中2,5-已二酮的含量,并依据WS/T 243-2004<职业接触正己烷的生物限值>,将含量超出和未超出生物限值的工人分为高接触组和低接触组,使用酶联免疫吸附法测定工人血清中MBP水平.结果 接触组工人尿中2,5-己二酮含量均值为(3.10±1.35)mg/L,对照组尿中2,5-已二酮含量均小于最低检出限(0.5mg/L).低接触组和高接触组工人血清中MBP表达的水平分别为(1.62±0.23)和(2.43±0.24)μg/L,明显高于对照组[(0.78±0.12)μg/L],差异均有统计学意义(P<0.01).经双变量Pearson相关分析,血清中MBP表达水平与尿中2,5-已二酮的含量呈正相关(r=0.781,P<0.01).结论 正已烷接触可导致人体血清中MBP表达水平升高,血清中MBP可作为正已烷接触的效应标志物.

Abstract：

Objective To explore the effects of n-hexane on expression of serum myelin proteins (MBP) in workers occupationally exposed to n-hexane.Methods In this study,269 workers exposed to n-hexane for more than one year and 104 subjects not exposed to n-hexane served as the exposure group and the control group,respectively.The urinary 2,5-hexanedione levels in all subjects were detected.On the basis of urinary 2,5-hexanedione levels,the exposure group was divided into the high exposure sub-group and low exposure sub-group.The serum myelin basic protein (MBP) levels were measured by ELISA kit.Results The mean concentration of urinary 2,5-hexanedione in the exposed group was (3.10±1.35) mg/L,The concentration of urinary 2,5-hexanedione in the control group was undetectable.The levels of serum MBP in the high exposure sub-group and low exposure sub-group were (2.43±0.24) and (1.62 ±0.23) (μg/L,respectively,which were significantly higher than that (0.78±0.12) μg/L in the controls (P<0.01).Pearson correlation analysis showed the positive correlation between serum MBP levels and urinary 2,5-hexanedione levels (r =0.781,P<0.01).Conclusion The results of present study showed that the serum MBP levels of workers occupationally exposed to n-hexane significantly elevated,and the serum MBP can serve as the effective biomarker of n-hexane exposure.     

大蒜油对正己烷染毒小鼠毒性拮抗作用

目的探讨大蒜油减少小鼠正己烷活性代谢产物的生成作用,为减少正己烷中毒提供实验依据。方法健康成年昆明小鼠,随机分为正己烷染毒组和大蒜油干预组,分别灌胃给予正己烷和大蒜油+正己烷,取血,分离血清经乙酸乙酯萃取后,气相色谱法测定血清中2,5-己二酮(2,5-HD)含量。结果小鼠经正己烷单次灌胃染毒后测定血清2,5-HD含量为(0.14±0.14)μg/mL,10 h后达峰值(24.63±3.52)μg/mL,至染毒后20 h降至(0.02±0.04)μg/mL;正己烷染毒前后给予大蒜油使小鼠6h血清2,5-HD含量分别较单纯染毒组降低32.1%(P<0.01)、24.4%(P<0.05);提前给予大蒜油使小鼠4～14 h含量降低26%～54%不等,其中染毒后4、6、8、10 h与单纯染毒组比较,差异有统计学意义(P<0.05或P<0.01),但大蒜油并未改变正己烷染毒小鼠2,5-HD含量曲线的形状和达峰时间。结论大蒜油可抑制正己烷染毒小鼠2,5-HD的产生,降低血清2,5-HD水平,降低正己烷毒性。     

正己烷对人体血清髓鞘P0与P2蛋白抗体的影响

目的 了解正己烷对人体血清髓鞘P0蛋白抗体与P2蛋白抗体表达的影响.方法 选取接触正己烷1年以上的工人269名作为接触组,同时选取未接触正己烷的工人104名作为对照组,测定工人尿中2,5-己二酮的含量,并依据WS/T243-2004<职业接触正己烷的生物限值>将含量超出和未超出生物限值的工人分别设为高接触组和低接触组,进一步使用酶联免疫吸附法测定工人血清中P0抗体、P2抗体的水平.结果 正己烷接触组工人尿中2,5-己二酮含量均值为(3.10±1.35)mg/L,对照组尿中2,5-己二酮含量均低于最低检出限.接触组工人血清中P0抗体(IgG、IgM)和P2抗体(IgG、IgM)表达均明显增加,与对照组相比,差异有统计学意义(P＜0.01),但接触组之间差异无统计学意义(P＞0.05).结论 正己烷可导致人体血清中P0抗体以及P2抗体升高,血清中P0抗体以及P2抗体可作为正己烷接触的易感性标志物,这将有助于正己烷职业中毒的早期发现与治疗,同时也为制定卫生标准提供新的理论依据.

Abstract：

Objective Exploring the effects of n-hexane on expression of serum myelin proteins in occupational exposure workers, and finding the early biomarker of n-hexane exposure. Methods In the study, 373 subjects were recruited, 269 exposure workers (work experience of more than 1 year)and 104 nonexposure workers were selected. Firstly examined the level of urinary 2,5-hexanedione in the two groups,based on urinary 2,5-hexanedione biological limit value (4 mg/L), the exposed group was divided into highexposed group and low-exposed group. And then collected blood samples and extracted serum. Human peripheral myelin protein zero (PO) antibody (IgG, IgM) and human peripheral myelin protein two(P2)antibody (IgG, IgM) analysis was performed according to ELISA kit. Results The concentration of urinary 2,5-hexanedione in the exposed group was (3.10± 1.35 ) mg/L. The level of PO antibody (IgG, IgM ) and P2 antibody (IgG, IgM) in the high-exposed group and low-exposed group were both higher than that in the controls (P＜0.01). Conclusion P0 antibody and P2 antibody could be used as the early biomarkers of nhexane exposure, which not only evaluate the occupational hazards in the early, but also provide the policy maker with scientific evidence.     

顶空-气相色谱质谱法测定血中正己烷代谢物2,5-己二酮

目的建立顶空-气相色谱质谱法测定血中正己烷代谢产物2,5-己二酮的方法。方法 3 ml血样加入内标物喹啉后,置70℃水浴40 min,经HP-5柱分离,内标工作曲线法定量。结果血中2,5-己二酮浓度在0.4μg/ml~1mg/ml时线性关系良好,相关系数为0.9994。方法的精密度相对标准偏差在5.7%~8.1%之间,血液样品加标回收率在89.2%~103.6%之间,方法检出限为0.2μg/ml。应用该法测定职业正己烷接触者53名和非正己烷接触者30名血中2,5-己二酮,结果显示职业正己烷接触者血中2,5-己二酮含量明显高于非正己烷接触者,并与接触正己烷浓度呈正线性相关(P0.01)。结论建立的顶空气相色谱法测定2,5-己二酮方法简便、快速、干扰少,可用于职业接触正己烷的生物监测。     

CYP2E1在大蒜油拮抗正己烷神经损伤中的作用

目的 研究CYP2E1在大蒜油(garlic oil,GO)阻止正己烷(n-hexane)致大鼠周围神经损伤的作用及其机制.方法 雄性Wistar大鼠50只,随机分为正常对照组、GO对照组、正己烷模型组、GO低剂量加正己烷组和高剂量加正己烷组(n=10).模型组及GO低、高剂量组大鼠分别给予2000 mg/kg正己烷灌胃;GO低、高剂量组大鼠在正己烷灌胃前1h分别给予40、80 mg/kg GO灌胃,GO对照组给予80 mg/kg,每周6次,持续10周.每2周测步态评分,监测大鼠周围神经损伤情况.于第10周末,断头处死大鼠,检测肝组织中CYP2E1表达及活力的改变,以及血清中2,5-己二酮(2,5-HD)含量的变化.结果 与正常对照组相比,GO对照组大鼠肝脏中CYP2E1含量及活力分别下降83.1％和48.3％,且差异均有统计学意义(P＜0.01);与正常对照组相比,模型组大鼠肝脏中CYP2E1含量及活力分别升高122.5％和72.2％,且差异均有统计学意义(P＜0.01);与模型组相比,GO低、高剂量组大鼠肝脏中CYP2E1含量分别降低32.9％和39.1％,且CYP2E1活力分别降低27.4％和44.5％,差异均有统计学意义(P＜0.01);与模型组相比,GO低、高剂量组大鼠血清中2,5-HD含量分别下降47.7％和78.7％,且差异均有统计学意义(P＜0.01).各组步态评分显示,模型组及GO低、高剂量组均明显高于对照组,但GO低、高剂量组低于模型组,差异有统计学意义(P＜0.05).结论 GO能够有效拮抗正己烷的外周神经损伤,其机制可能与肝脏中CYP2E1含量及活力降低,使正己烷代谢为2,5-HD减少有关.     

地塞米松预处理对大鼠光气吸入性肺损伤基质金属蛋白酶-9表达的影响

Objective To investigate the effects of dexamethasone on expression of matrix metalloproteinase-9 (MMP-9) in rats with acute lung injury induced by phosgene. Methods The rats were randomly divided into 3 groups: normal control group that consists of the rats with air exposure, phosgene group that consists of the rats with phosgene exposure and dexamethasone group that consists of the rats with phosgene exposure after 2.5 mg/kg dexamethasone being injected. Wet and dry ratio of the lung (W/D) was calculated, and leukocyte count and total protein content of bronchoalveolar lavage fluid (BALF) were recorded at 2 h after exposure. The concentrations of MMP-9 in the serum and BALF were measured by enzyme-linked immunosorbent assay. The pathologic changes of lung tissues were observed under light microscopy. The immunohistochemistry and the RT-PCR were used to detect the contents of MMP-9 in the lung tissue. Results Compared with phosgene group, the lung W/D, protein content and WBC count in of BALF dexamethasone group was significantly decreased (P＜0.01). MMP-9 levels of the serum and BALF in dexamethasone group were (4.799±0.043) μg/L and (15.052±0.029) μg/L, respectively, which were significantly lower than those [(9.439±0.100) and (20.640±0.446) μg/L] in phosgene group (P＜0.01). Compared with phosgene group (2.789±0.282), the expression level(1.183±0.260) of lung M MP-9 mRNA in dexamethasone group was significantly lower than that in phosgene group (P＜0.01).Histological experimental results showed the marked hyperemia and thickening of alveolar wallsand stroma cells infiltrating and more visible alveolar structure damage of alveolar walls in phosgene group while the alveolar structure and the alveolar walls were clear and slightly thickened with inflammatory cells in dexamethasone group. Immunohistochemical results showed that MMP-9 protein expression levels of lung and brochus tissues in normal control group and dexamethasone group were weakly positive, which in phosgene group were strongly positive. Conclusion Dexamethasone has a beneficial effects on acute lung injury induced by phosgene in rats due to the inhibiting MMP-9.     

大蒜油对正己烷致大鼠周围神经病变影响

目的探讨大蒜油(garlic oil,GO)对正己烷(n-hexane)所致大鼠周围神经病变的影响。方法雄性SD大鼠60只,随机分为对照组、模型组、大蒜油低、高剂量组,灌胃给予大蒜油40,80 mg/(kg.bw),1 h后灌胃给予正己烷2 500 mg/(kg.bw),模型组灌胃给予等量正己烷,每周5次,持续8周,测定神经行为学指标。结果模型组大鼠后肢撑力指数(9.58 cm)与对照组(7.28 cm)比较明显增加(P0.05),大蒜油低、高剂量组后肢撑力指数分别为7.94和6.99 cm,与对照组比较,差异无统计学意义(P0.05);对照、模型、大蒜油低、高剂量组倒挂网格指数分别为10.0,3.0,6.0和8.0 s,大蒜油组倒挂网格指数低于对照组(P0.05),高于模型组(P0.05);大蒜油组步态明显优于模型组(P0.05)。结论大蒜油具有保护正己烷所致大鼠周围神经病变的作用。     

两种拟除虫菊酯类农药抗雄激素活性的Hershberger实验研究

目的 研究两种拟除虫菊酯类农药氯氰菊酯和甲氰菊酯在体内的抗雄激素作用.方法 6周龄雄性SD大鼠去势后恢复一星期,按体重随机分为8组,每组6只,包括阴性对照组,氯氰菊酯与甲氰菊酯低、中、高剂量组,阳性对照组.各组动物均皮下注射丙酸睾酮(TP)100μg/(kg·d)连续7 d.阴性对照组、两种拟除虫菊酯农药组和阳性对照组分别皮下注射给予花生油、氯氰菊酯[45、90、180mg/(kg·d)]、甲氰菊酯[10、20、40mg/(kg·d)]、氟他胺(20mg/kg),连续7 d,观察大鼠性附属组织及血清激素水平的变化.结果 两种拟除虫菊酯类农药各剂量组与阴性对照组比较,大鼠性附属器官精囊腺、背侧前列腺、腹侧前列腺和提肛肌重量,以及大鼠血清睾酮(T)、促卵泡激素(FSH)和黄体生成素(LH)水平差异均无统计学意义.阳性对照组与阴性对照组比较,大鼠各性附属器官重量均降低,大鼠LH水平升高,差异均具有统计学意义.结论 氯氰菊酯和甲氰菊酯对去势雄性大鼠的性附属器官重量和血清T、FSH和LH水平无明显影响,未显示出抗雄激素活性.

Abstract：

Objective To observe the anti-androgenic activity of two pyrethroids (cypermethrin and fenpropathrin) in vivo. Methods SD rats aged 6 weeks were castrated ,and then housed for one week. The rats were randomly divided into groups, six in each: negative control group, cypermethrin and fenpropathrin group, positive control group. The rats were subcutaneously injected with testosterone propionate (TP) 100 μg/(kg·d) for 7 consecutive days. Peanut oil, cypermethrin [ 45, 90, 180 mg/(kg·d)], fenpropathrin[10, 20, 40 mg/ (kg·d) ], fiutamide[ 20 mg/(kg·d) ] were subcutaneously injected for 7 consecutive days at the same time. The sex accessory glands and serum hormone were detected. Results Compared with the negative group, no significant differences were observed in the sex accessory glands/tissues (seminal vesicles with coagulating glands, dorsolateral prostate, the ventral prostate and levator ani muscles) and the levels of serum hormones of the pyrethroids groups. Compared with the negative group, the masses of all the sex accessory glands/tissues decreased significantly in the positive group . Compared with the negative group, the level of LH increased significantly in the positive group. Conclusion No obvious anti-androgenic effects induced by cypermethrin and fenpropathrin in castrated SD rats has been observed.     

利尿剂在三聚氰胺及三聚氰酸致大鼠急性肾损伤中的治疗作用

Objective To investigate the effect of diuretic (furosemide) therapy on kidney injury induced by melamine and cyanuric acid in rats. Methods 36 male Spragne Dawley rats were random disided into 3 groups. Group A was treated with 2mL of water daily, group B was treated with melamine and cyanuric acid ( each 100 mg/kg) daily for 4 days and then 2ml of water daily, group C was treated with the same as group B at the first 4 days and then treatment with furosemide (20mg/kg) daily. Samples of blood and 24h urine were collected to detective biochemical indexes, and kidney sections were performed on days 4 and 11 ( each end point, n = 6). The kidneys were observed with histopathology and renal crystal deposition scores were determined. Results On the 4th day, group B and group C were resulted in acute kidney injury such as oliguria [ ( 3. 39 ± 1.02 ) ml, ( 3. 20 ± 0. 86 ) ml ] and high serum creatinine [ ( 153.54 ±27. 08)μmol/L, (160. 11 ± 19. 55)μmol/L] and renal melamine cyanurate crystal were found in the renal tissues. On the 11th day, the renal crystal deposition score in the rats was reduced by 9. 52% ( P >0. 05). Compared with those of the 4th day in group B, it reduced by 63.63%( P <0.05) in group C. Urine volume were increased significantly compared with those of the 4th day( P < 0. 05 ) in group C [ from (3.20±0. 86)ml to (25.96 ±5.97)ml] and group B [ from(3. 39 ± 1.02)ml to (8. 57 ± 1.66)ml] , and Urine volume in group C was increased significantly more than that in group B ( P < 0. 05 ). The serum creatinine was obviously reduced as compared with those of the 4th day in group B and C( P <0.05), from[ (153. 54±27.08) μmol/L] to [ ( 106. 10 ±5.53) μmol/L] in group B and from [ ( 160. 11 ± 19. 55) μmol/L] to [ (67. 17 ± 12. 80 ) μmol/L] in group C, but the serum creatinine in group B was still higher than that in group A and C ( P < 0. 05). Conclusions Furosemide can attenuate the damage of acute kidney injury induced by melamine and cyanuric acid.     

双酚A在染毒雄性大鼠血清中时间-浓度关系

目的 探讨经口给予雄性大鼠双酚A(bisphenol A,BPA)后,血清中BPA时间-浓度关系.方法 66只无特定病原体(specific pathogen free,SPF)级雄性SD大鼠应用数字表法随机分为10个实验组和1个对照组,每组6只.各实验组大鼠一次性灌胃给予300 mg/kg剂量的BPA后,在0.5、1、2、4、6、12、24、36、60、84 h时间点各采集一组大鼠血液,分离出血清,用荧光-高效液相色谱法检测血清中游离型和总BPA浓度.结果 大鼠一次性经口染毒后,1 h血清中总BPA浓度最高,达17.13μg/ml,2 h血清中BPA浓度急剧下降,24 h血清中总BPA浓度又上升到15.18μg/ml,持续观察84 h,血清中BPA仍有0.51μg/ml.游离型BPA含量较低,染毒0.5 h,血清中游离型BPA浓度为0.57 μg/ml,而后急剧下降,1 h下降到0.06μg/ml,4 h下降到0.03μg/ml,36 h仅有0.01μg/ml.在染毒0.5 h,游离型BPA在血清中所占的百分率最高,为血清总BPA的4.15%(0.57/13.73),其他各时间点血清中游离型BPA所占的百分率均较低.结论一次性经口给予大鼠BPA后,血清中主要以结合型BPA存在,血清总BPA随染毒时间的延长出现双峰现象,可能与BPA代谢过程中肝肠循环有关.     

肝脏中乙醇脱氢酶活力在大蒜油阻止大鼠正己烷神经损伤中的变化

目的 研究大蒜油(garlic oil,GO)对正己烷(n-hexane)所致大鼠周围神经损伤的保护作用及其机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、模型组、大蒜油低剂量组和高剂量组(n=10);正常对照组动物给予等体积生理盐水灌胃,模型组和大蒜油低、高剂量组大鼠分别给予2000mg/kg正己烷灌胃,大蒜油低、高剂量组大鼠于正己烷灌胃前1 h分别给予40和80mg/kg大蒜油灌胃,每周6次,持续10周.每周测步态评分和转棒指数,监测大鼠周围神经损伤情况.10周末,断头处死大鼠,测定肝组织中乙醇脱氢酶(ADH)、丙二醛(MDA)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)、抑制羟基自由基能力.结果 与正常对照组相比,模型组大鼠步态评分明显升高,差异有统计学意义(P＜0.01),而转棒指数明显下降.肝脏中ADH活力[(3.64±0.73)U/mgpro]上升49.8%,肝脏中GSH-Px、T-AOC和抑制羟基自由基能力水平下降[分别为(182.0±41.7)、(1.10±0.27)、(162.1±26.1)U/mg pro],MDA含量[(1.89±0.42)nmol/mg pro]上升,与正常对照组[分别为(2.43±0.54)U/mgpro、(273.3±48.8)U/mg pro、(1.89±0.42)U/mg pro、(196.3±36.9)U/mg pro、(1.28±0.28)nmol/mg pro]的差异均有统计学意义(P＜0.05或P＜0.01).与模型组相比,大蒜油低、高剂量组大鼠步态评分明显降低,差异有统计学意义(P＜0.05),而转棒指数明显升高,差异均有统计学意义(P＜0.05或P＜0.01);与正常对照组相比,肝脏中ADH活力分别降低了25.3%和86.0%,GSH-Px、GSH、T-AOC及抑制羟基自由基能力水平明显上升,MDA含量明显下降,差异均有统计学意义(P＜0.05或P＜0.01).结论 大蒜油能够有效拮抗正己烷诱导所致的外周神经损伤,其机制可能与肝脏ADH活力降低有关.     

大、小鼠吸收和代谢双酚A的差异

目的 探讨相同剂量双酚A(bisphenol A,BPA)经口染毒后,引起大、小鼠血清BPA浓度差异的机制.方法 无特定病原体(specic pathogen free,SPF)级雄性SD大鼠和ICR小鼠各18只,一次性经口给予300 mg/kg的BPA后,在第0.5、1.0、12.0小时时间点各采集6只大、小鼠血液,用荧光-高效液相色谱法(fluorescence-high performance liquid chromatography,FL-HPLC)检测血清中BPA浓度;大、小鼠各6只采用原位小肠吸收模型循环灌流100 ml 0.1 mmol/L BPA灌流液,用FL-HPLC法分别检测第0.5、1.0、2.0小时时间点灌注液中BPA浓度和灌流后2.0 h血清中的浓度;采用逆转录PCR(RT-PCR)方法检测大、小鼠肝脏尿苷二磷酸葡萄糖醛酸转移酶2B1(UDP-glucuronosyltransferase 2B1,UGT2B1)mRNA的表达水平,并采用FL-HPLC法检测UGT2B1的酶活性;大、小鼠各6只禁食24 h后,一次性经口给予300 ms/kg BPA,收集24 h粪便,用FL-HPLC法检测粪便中BPA含量.结果 300 ms/kg BPA经口染毒后第0.5、1.0、12.0小时时间点小鼠血清中BPA浓度分别为(66.57±14.95)、(51.16±16.06)、(22.73±5.00)μg/ml,大鼠血清中BPA浓度分别为(15.63±5.65)、(18.34±5.02)、(7.65±2.58)μg/ml,各时间点小鼠均高于大鼠,差异有统计学意义(F值分别为50.660,17.957,8.420,P值均＜0.05);0～、0.5～、1.0～2.0 h小鼠小肠各时间段吸收速率分别为(10.20±4.20)、(1.49±0.67)、(1.31±0.55)μg·cm-2·min-1均高于大鼠相应时间段吸收率[(1.87 ± 0.69)、(0.47±0.13)、(0.36 ± 0.08)μg·cm-2·min-1],差异均有统计学意义(F值分别为14.954、8.877、11.536,P值均＜0.05).0.1 mmol/L BPA灌肠2 h后小鼠血清中的BPA浓度为(22.64±4.35)μg/ml,高于大鼠的(4.13±0.83)μg/ml,差异有统计学意义(F=74.643,P=0.000);大鼠肝脏中BPA代谢酶UGT2B1 mRNA的表达水平和酶活性明显高于小鼠;300 mg/kg BPA经口染毒24 h后,大鼠经粪便排出的BPA量为(1.50±0.32)mg/g,高于小鼠的(0.57±0.35)ms/g,差异有统计学意义(F=21.215,P=0.001).结论 大、小鼠经口给予300 mg/kg BPA染毒后,由于小鼠肠吸收BPA的能力高于大鼠,而大鼠代谢及排出BPA能力高于小鼠,引起小鼠血清中BPA的浓度明显高于大鼠.     

2,5-己二酮不同作用时间对大鼠坐骨神经P_0蛋白及血清P_0蛋白抗体水平的影响

目的探讨正己烷代谢产物2,5-己二酮不同作用时间对大鼠坐骨神经髓鞘结构蛋白P0蛋白及外周血中P0蛋白抗体水平的影响。方法选用400mg/kg2,5-己二酮每日经口灌胃染毒Wistar大鼠,观察大鼠的一般状况改变,分别于第0、1、2、3、4周取材,采用免疫组化技术观察不同染毒时间大鼠坐骨神经横断面P0蛋白表达水平,并采用酶联免疫吸附试验检测不同染毒时间,大鼠外周血中P0蛋白抗体的水平。结果随着染毒时间的延长,大鼠逐渐出现明显的中毒症状。P0蛋白在坐骨神经横断面呈不均匀分布,髓鞘较轴索明显;未染毒大鼠坐骨神经横断面P0蛋白呈较高水平表达,随着染毒时间的延长,坐骨神经横断面P0蛋白表达水平有逐渐降低的趋势。染毒0、1、2、3和4周大鼠外周血中P0蛋白抗体阳性率分别为33.3%、26.7%、46.7%、46.7%和84.6%。外周血中P0蛋白抗体的阳性率随染毒时间延长呈现明显增加的趋势(χ2=11.007,P0.05)。结论正己烷代谢产物2,5-己二酮能够破坏大鼠周围神经髓鞘,降低坐骨神经中P0蛋白的水平,提高外周血中P0蛋白抗体的水平。     

盐酸戊乙奎醚治疗百草枯急性肺损伤的实验研究

目的 研究盐酸戊乙奎醚注射液(长托宁)对百草枯(PQ)急性肺损伤的干预作用及其机制.方法 选取80只健康成年雄性Wistar大鼠随机分为对照组(10只)、100 mg/kg PQ染毒组(10只)、100 mg/kg PQ染毒+33 μg/kg长托宁治疗组(30只)、100 mg/kg PQ染毒+66μg/kg长托宁治疗组(30只).2个治疗组分别于给药后的36、72 h及7 d处死.HE染色行肺组织病理学检查.取肺组织检测基质金属蛋白酶-2(MMP-2)、小窝蛋白-1、羟脯氨酸(HYP),取血清、支气管肺泡灌洗液(BALF)进行内皮素(ET)的检测.结果 病理学检查证实大鼠急性肺损伤模型复制成功.染毒组大鼠肺组织中MMP-2、HYP及血清、BALF中ET含量分别为(1.77±0.40)μg/g、(2.91±0.79)μg/g、(505.23±124.69)μg/ml、(640.38±136.60)μg/ml,均高于对照组[分别为(0.95±0.66)μg/g、(1.48±0.69)μg/g、(95.48±46.01)μg/ml、(200.40±88.39)μg/ml]差异均有统计学意义(P<0.05);长托宁治疗组的上述各指标均较染毒组下降,差异亦有统计学意义(P<0.05).染毒组大鼠肺组织中小窝蛋白-1含量为(1.77±0.82)μg/g,明显低于对照组[(5.39±1.68)μg/g],差异有统计学意义(P<0.05);长托宁治疗组的小窝蛋白-1含量均高于染毒组,差异有统计学意义(P<0.05).结论 长托宁可降低PQ染毒大鼠肺组织MMP-2、HYP以及血清和BALF中ET的含量,提高小窝蛋白-1的含量,进一步减轻百草枯所致的肺损伤.     

亚硒酸钠与核黄素联合暴露对高脂饮食大鼠血脂及血清肝生化指标的影响

目的研究亚硒酸钠与核黄素联合暴露对高脂饮食雄性大鼠血脂及血清肝生化指标的影响。方法将60只健康SPF级雄性SD大鼠按体重随机分为空白对照组(10只)和高脂组(50只),分别给予基础饲料和高脂饲料;喂养4周后,将50只高脂组大鼠按照血脂水平和体重随机分为5组,分别为高脂对照组、1.84μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组、18.40μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组、1.84μg/kg亚硒酸钠+3.50 mg/kg核黄素干预组和18.40μg/kg亚硒酸钠+3.50 mg/kg核黄素干预组,每组10只。采用灌胃方式进行染毒,同时,空白对照组和高脂对照组给予相同体积的生理盐水,染毒容量为10 ml/kg,每天1次,连续60 d。分别于第0(染毒前)、20、40、60天,测定大鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平;并于第60天,检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)的水平。结果与空白对照组比较,染毒期间高脂对照组及各干预组大鼠血清TC、TG、LDL-C的水平均升高,除第60天时1.84μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组大鼠血清TG水平外,差异有统计学意义(P0.05);而血清HDL-C水平均未见显著变化。与高脂对照组相比,第20、40天时1.84μg/kg亚硒酸钠+0.70mg/kg核黄素干预组大鼠血清TC、TG的水平及1.84μg/kg亚硒酸钠+3.50 mg/kg核黄素干预组大鼠血清TG的水平以及第60天时1.84μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组大鼠血清TC、TG、LDL-C的水平及18.40μg/kg亚硒酸钠+0.70mg/kg核黄素干预组大鼠血清TC的水平均下降,差异有统计学意义(P0.05);而各干预组大鼠血清HDL的水平均无明显改变。与空白对照组比较,高脂对照组、18.40μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组和1.84μg/kg亚硒酸钠+3.50mg/kg核黄素干预组大鼠血清ALT的水平以及高脂对照组、18.40μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组和18.40μg/kg亚硒酸钠+3.50 mg/kg核黄素干预组大鼠血清AST的水平均升高,差异有统计学意义(P0.05)。与高脂对照组相比,仅1.84μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组大鼠血清ALT的水平降低,差异有统计学意义(P0.05);1.84μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组、18.40μg/kg亚硒酸钠+0.70 mg/kg核黄素干预组以及1.84μg/kg亚硒酸钠+3.50 mg/kg核黄素干预组大鼠血清AST的水平降低,差异均有统计学意义(P0.05)。结论适量亚硒酸钠与核黄素联合暴露可以拮抗高脂饮食所致雄性大鼠血脂及血清肝生化指标的升高。     

骨化三醇对SD大鼠经链脲佐菌素诱导糖尿病发生过程的影响

目的探讨骨化三醇[1,25（OH）2D3]对链脲佐菌素（streptozocin,STZ）所致SD大鼠糖尿病发生过程的影响,为人类1型糖尿病的预防提供实验依据。方法将28只雄性SD大鼠随机分为3组。20只大鼠采用STZ造成糖尿病模型,其中1,25（OH）2D3组（n=10）造模前4周接受1,25（OH）2D31μg/（kg·d）溶于0.05 ml花生油灌胃,STZ对照组（n=10）造模前4周采用花生油灌胃,0.05ml/d。STZ对照组和1,25（OH）2D3组均于实验第5周开始第1天腹腔注射福氏完全佐剂（CFA）,0.5 ml/只,第2天按30 mg/kg STZ枸椽酸溶液腹腔注射,以STZ对照组全部成模为准,停止造模;成模后2周处死。其余8只为正常对照组,采用花生油灌胃,0.05ml/d,灌胃4周,不注射STZ。观察1,25（OH）2D3对STZ所致SD大鼠糖尿病发病情况及对胰岛素、血糖的影响。结果 STZ对照组10只大鼠全部造模成功,1,25（OH）2D3组10只大鼠中6只成模,造模成功率差异有统计学意义（P〈0.05）。1,25（OH）2D3组血糖曲线下面积（AUC）为（21.301±4.699）mmol·h/L,明显低于STZ对照组[（31.183±4.567）mmol·h/L],差异有统计学意义（P〈0.05）。1,25（OH）2D3组胰岛素AUC为（1.105±0.356）μg·h/L,明显高于STZ对照组[（0.472±0.162）μg·h/L],差异有统计学意义（P〈0.05）。血清1,25（OH）2D3水平与胰岛素AUC呈正相关,而与血糖AUC呈负相关,有统计学意义（r=0.517,P=0.04;r=-0.562,P=0.02）。结论 1,25（OH）2D3对STZ所致SD大鼠糖尿病的发生有一定的预防作用。