姜黄素抑制TLR4/HMGB1通路保护脂多糖诱导急性肺损伤的作用

目的探讨姜黄素对脂多糖(LPS)诱导急性肺损伤的保护作用及相关机制。方法将24只SD大鼠随机分为对照组、LPS组和LPS+姜黄素组,每组8只。检测肺损伤指标(氧分压、肺干湿重比、肺病理评分)、肺组织炎症反应程度[肿瘤坏死因子(TNF)-α、白介素(IL)-6、单核细胞趋化蛋白(MCP)-1以及肺组织中Toll样受体4(TLR4)、高迁移率族蛋白B1(HMGB1)表达水平]。结果LPS组氧分压显著低于对照组(P<0.05),而肺干湿重比、肺病理评分、TNF-α、IL-6、MCP-1、TLR4、HMGB1表达水平显著高于对照组(P<0.05);LPS+姜黄素组氧分压高于LPS组(P<0.05),肺干湿重比、肺病理评分、TNF-α、IL-6、MCP-1、TLR4、HMGB1表达水平显著低于LPS组(P<0.05)。结论姜黄素可能通过抑制TLR4/HMGB1通路,降低肺炎症反应程度,发挥保护LPS诱导急性肺损伤作用。     

参附注射液对大鼠机械通气相关性肺损伤的保护作用及其机制

目的 探讨参附注射液(Shenfu injection,SF)对大鼠机械通气(mechanical ventilation,MV)相关性肺损伤的保护作用及其机制. 方法 40只健康成年雄性Wister大鼠采用随机数字表法分为4组,每组10只:对照组(C组)、正常潮气量MV组(N组)、大潮气量MV组(L组)、大潮气量MV+SF处理组(SF组).C组保留自主呼吸;N组、L组和SF组MV4h,潮气量分别设置为8～10 ml/kg、40 ml/kg、40 ml/kg,SF组于MV前15 min静脉注射SF 10 ml/kg.实验结束处死动物,收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),测定BALF中总蛋白、IL-1β、IL-18和TNF-α的浓度;取肺组织,测量湿/干重比(wet/dry,W/D),采用免疫组化法检测肺组织NF-κB的表达,观察病理学改变并进行肺损伤评分. 结果 SF组BALF中TNF-α、IL-1β、IL-18浓度分别为(65±11)、(47±9)、(58±8) ng/L,较L组(99±7)、(69±7)、(86±7) ng/L明显降低(P＜0.05);SF组大鼠肺损伤评分、W/D、肺组织NF-κB光密度值分别为(8.5±1.8)分、(5.0±1.6)、(0.32±0.28),较L组(14.1±2.7)分、(5.5±1.8)、(0.54±0.33)均明显降低(P＜0.05). 结论 SF可减轻大鼠MV相关性肺损伤,其机制可能与SF抑制肺内NF-κB通路的活性且降低肺内炎性因子的释放有关.     

维生素C减轻失血性休克引起的大鼠肺树突细胞聚集及肺损伤

目的 探讨失血性休克对大鼠肺组织树突细胞聚集及肺损伤的影响,以及维生素C的保护作用.方法 SD大鼠(6～7周龄)42只,按数字随机法随机分为对照组、失血性休克2h、6h、24 h组及失血性休克+维生素C2h、6h、24 h组等7组,每组各6只.以股动脉放血法建立大鼠失血性休克模型.免疫组化和逆转录聚合酶链反应(RT-PCR)法检测肺组织树突细胞特异性细胞间粘附分子非整合素蛋白-3(DC-SIGN)表达情况.同时检测肺TNF-α、IL-6含量,髓过氧化物酶(MPO)活性,并进行肺损伤评分.结果 对照组肺中DC-SIGN蛋白表达很少,失血性休克组表达显著升高(P＜0.05),失血性休克后2h肺DC-SIGNmRNA含量就开始增高,休克后24 h仍呈升高趋势.失血性休克组大鼠肺TNF-α、IL-6 mRNA水平升高(P＜0.05),MPO活性增加(P＜0.05),病理损伤显著加重(P＜0.05).失血性休克大鼠在复苏前给予维生素C干预后,上述现象均减轻(P＜0.05).结论 失血性休克可能通过促进肺组织树突细胞聚集引起急性肺损伤.维生素C对这一过程有抑制作用.     

Effects of cyclooxygenase - 2 inhibitor on peritoneal function and angiogenesis in uremic peritoneal dialysis rats

Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on angiogenesis and peritoneal function of uremic peritoneal dialysis rats. Methods Forty - eight male SD rats were selected, and they were randomly divided into five groups: normal control group(n=8), sham operation group(n=8), uremia group(5/6 nephrectomy, n=8), PD group [4.25% PD solution, 2 weeks PD model(n=8) and 4 weeks PD model(n=8)], PD + celecoxib intervention group[treated by celecoxib(20 mg/kg) via oral gavage, n=8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures, functions, peritoneal tissue capillary density (microvessel density, MVD) and COX-2, vascular endothelial growth factor (VEGF) expression level, and the impacts of celecoxib on uremic peritoneal dialysis rats peritoneal angiogenesis and peritoneal function were study. Results With the conduct of the peritoneal dialysis, peritoneal thickness increased, the inflammatory cells infiltrated, peritoneal equilibration test (PET) showed that ultrafiltration volume decreased significantly (P＜0.05), the amount of glucose transport rate rised significantly (P＜0.05), but the celecoxib could improve net ultrafiltration volume (P＜0.05), and reduce the glucose transport rate (P＜0.05). The peritoneal tissue MVD and COX - 2, VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group (all P＜0.05), were significantly lower in PD + Celecoxib intervention group than that in uremia group (P＜0.05). The correlation analysis showed that the level of COX-2 protein expression with MVD, VEGF protein expression was positively correlated (both P＜0.05), the level of VEGF protein expression and MVD was positively correlated (P＜0.05). Conclusions In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised, and the capillaries production increased in peritoneal tissue. Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats. Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats, possibly through inhibition of COX-2 expression to reduce the production of VEGF.     

异丙酚联合机体低氧预处理对大鼠肺缺血再灌注损伤的影响

目的 探讨异丙酚联合机体低氧预处理对大鼠肺缺血再灌注损伤的影响.方法 健康雄性SD大鼠90只,体重250～320 g,随机分为5组(n=18):假手术组(S组)、肺缺血再灌注组(IR组)、异丙酚组(P组)、机体低氧预处理组(WBHP组)和异丙酚联合机体低氧预处理组(PW组).IR组采用阻断左肺门45 min后再灌注的方法制备大鼠单肺缺血再灌注损伤模型,P组夹闭左肺门前30 min持续静脉输注异丙酚30 mg·kg-1·h-1;WBHP组夹闭左肺门前先行机体低氧预处理;PW组夹闭左肺门前30 min持续静脉输注异丙酚30 mg·kg-1·h-1和机体低氧预处理.分别于再灌注0.5、1、4 h时测定肺组织TNF-α、IL-1、IL-6和MDA的含量,SOD活性,计算肺湿干重比(W/D).结果 与S组比较,IR组、P组、WBHP组和PW组T1～3时肺组织TNF-α、IL-1、IL-6和MDA的含量及W/D升高,SOD活性降低(P＜0.05);与IR组比较,P组、WBHP组和PW组T1～3时TNF-α、IL-1、IL-6和MDA的含量及W/D降低,SOD活升高(P＜0.05);与P组和WBHP组比较,PW组T2,3时TNF-α和IL-6的含量及W/D降低,SOD活性升高,T3时IL-1和MDA的含量降低(P＜0.05).P组与WBHP组各指标差异无统计学意义(P＞0.05).结论 异丙酚联合机体低氧预处理减轻肺缺血再灌注损伤的作用较单独应用时强,可能与联合应用时抑制炎性反应的作用增强和抗氧化能力提高有关.     

早期生长反应因子-1在移植肺缺血再灌注过程中的炎症损伤作用

目的 探讨早期生长反应因子-1(EGR-1)在移植肺缺血再灌注过程中的炎症损伤作用.方法 选择SD大鼠作为供、受者,建立左肺移植模型.实验分为4组:再灌注1 h组、再灌注2 h组和再灌注4 h组,移植后对移植肺分别进行1、2和4 h的再灌注;选取未进行移植和再灌注的供肺作为对照组.采用荧光定量实时聚合酶链法检测各组肺组织中EGR-1和白细胞介素(IL)-1β mRNA 的相对表达量,并检测支气管肺泡灌洗液(BAL)中性粒细胞数、肺组织湿/干质量比(W/D)及髓过氧化物酶(MPO)活性等指标.结果 各再灌注组EGR-1和IL-1β mRNA的相对表达量均高于对照组,并且随着再灌注时间的延长而明显增高,4组间比较,差异均有统计学意义(P＜0.05).各组肺组织W/D、BAL中性粒细胞数以及MPO活性也均高于对照组,并且随着再灌注时间的延长而显著增高,4组间比较,差异均有统计学意义(P＜0.05),各组EGR-1 mRNA与IL-1β mRNA的表达呈显著的正相关(r=0.921,P＜0.01).各组EGR-1 mRNA的表达与BAL中性粒细胞数呈显著的正相关(r=0.876,P＜0.01).结论 EGR-1由肺缺血诱导产生和表达;在肺缺血再灌注过程中,通过IL-1β的参与,EGR-1发挥重要的炎症损伤作用.     

盐酸戊乙奎醚对体外循环致大鼠急性肺损伤的影响

目的 评价盐酸戊乙奎醚对体外循环(CPB)致大鼠急性肺损伤的影响.方法 成年雄性SD大鼠40只,4～6月龄,体重330～420 g,采用随机数字表法,将其随机分为4组(n=10):假手术组(S组)仅进行动脉和静脉穿刺置管;急性肺损伤组(ALI组)、低剂量盐酸戊乙奎醚组(PL组)和高剂量盐酸戊乙奎醚组(PH组)建立CPB模型;PL组和PH组分别在预冲液中加入盐酸戊乙奎醚0.6和2.0 mg/kg,ALI组加入等容量生理盐水,进行CPB1h.于CPB前和CPB结束后2h采集动脉血样,进行血气分析;于CPB结束后2h时采集上腔静脉血样,测定血浆TNF-α和IL-6的浓度;取肺组织测定含水量、MDA含量和谷胱甘肽过氧化物酶(GSH-px)活性,光镜下观察病理学改变.结果 与S组比较,ALI组、PL组和PH组CPB结束后2h时PaO2降低,肺组织含水量、MDA含量和血浆TNF-α和IL-6的浓度升高,肺组织GSH-px活性降低(P＜0.05);与ALI组比较,PL组和PH组CPB结束后2h时PaO2升高,肺组织含水量、MDA含量和血浆TNF-α和IL-6的浓度降低,肺组织GSH-px活性升高(P＜0.05),病理学损伤减轻;与PL组比较,PH组CPB结束后2h时PaO2升高,肺组织含水量、MDA含量和血浆TNF-α和IL-6的浓度降低,肺组织GSH-px活性升高(P＜0.05),病理学损伤减轻更明显.结论 盐酸戊乙奎醚0.6和2.0 mg/kg可减轻CPB致大鼠急性肺损伤,且与剂量有关,其机制与抑制脂质过氧化反应和炎性反应有关.     

维持性血液净化患者微炎症状态的临床研究

目的：观察血液透析患者与腹膜透析患者微炎症状态存在情况,比较两种不同类型血液净化治疗微炎症状态的差别。方法：选择我院透析中心血液透析患者58例,腹膜透析患者49例,健康对照组57例,空腹采取静脉血检测超敏CRP（hs-CRP）、IL-6、IL-8、TNF-α,比较各组数值的情况。结果：血液透析组、腹膜透析组超敏CRP（hs-CRP）、IL-6、TNF-α均高于健康对照组（P〈0.05）;IL-8均高于对照组,但无统计学差异（P〉0.05）。血液透析组与腹膜透析组比较,超敏CRP（hs-CRP）高于腹膜透析组（P〈0.05）;两组比较IL-6、IL-8、TNF-α均无统计学差异。结论：血液透析、腹膜透析患者均存在较高的微炎症状态,两者相比血液透析患者微炎症状态高于腹膜透析,但腹膜透析患者的前炎症因子与血液透析水平相同。     

盐酸戊乙奎醚预先给药对新生大鼠内毒素性急性肺损伤时NF-κB活性的影响

目的 探讨盐酸戊乙奎醚预先给药对新生大鼠内毒索性急性肺损伤时NF-kB活性的影响.方法 健康新生Wistar大鼠30只,雌雄不拘,日龄7 d,体重18～21 g,随机分为3组(n=10):对照组(C组)、急性肺损伤组(ALI组)和盐酸戊乙奎醚预先给药组(P组).采用腹腔注射内毒素3 mg/kg的方法制备急性肺损伤模型,P组腹腔注射盐酸戊乙奎醚0.5 mg/kg,30 min后制备模型,C组腹腔注射等容量生理盐水.于腹腔注射内毒素4 h时处死大鼠取肺,称重后计算肺湿,干重比,电镜下观察肺组织病理学结果,采用免疫组织化学法检测NF-kB p65的表达水平,采用酶联免疫吸附法测定TNF-α、IL-1 β及IL-10的含量.结果 与C组比较,ALI 组和P组肺湿/干重比、TNF-α、IL-1β、IL-10含量及NF-KB p65表达水平升高(P＜0.05);与ALI 组比较,P组肺湿/干重比、TNF-α、IL-1β、IL-10含量及NF-kBp65表达水平降低(P＜0.05).病理学结果显示:P组肺组织损伤程度较ALI组明显减轻.结论 盐酸戊乙奎醚预先给药可通过抑制肺组织NF-kB活化,降低炎性反应,减轻新生大鼠内毒素性急性肺损伤.     

Nod样受体蛋白3炎性体抑制剂格列苯脲对机械通气致小鼠急性肺损伤的保护作用

目的 探究Nod样受体蛋白3(Nod-like receptor protein-3,NLRP3)炎性体抑制剂格列苯脲对机械通气导致的小鼠急性肺损伤是否具有保护作用. 方法 28只7～9周的清洁级ICR雄性小鼠,按完全随机分组法分为4组:对照组(CON组,6只)、格列苯脲组(GLY组,6只)、机械通气组(VEN组,8只)和格列苯脲+机械通气组(GLY+VEN组,8只).VEN组和GLY+VEN组机械通气4h后与CON组及GLY组麻醉插管后4h测定肺泡灌洗液中蛋白含量及炎性细胞数量,测量肺组织湿/干重比(wet/dry,W/D),观察肺组织病理学改变,ELISA法检测肺组织IL-1β、IL-6、TNF-α的含量. 结果 VEN组肺泡灌洗液中蛋白浓度和细胞数量[(0.534±0.104) g/L和(3.4±0.7)×105/ml]比CON组[(0.167±0.021) g/L和(1.9±0.5) ×105/ml]升高(P＜0.01);GLY+VEN组肺泡灌洗液中蛋白浓度和细胞数量[(0.425±0.083) g/L和(2.4±0.6) ×105/ml]比VEN组下降(P＜0.05).VEN组肺组织W/D(5.1±0.5)与CON组(4.4±0.4)比较,差异有统计学意义(P＜0.01),GLY +VEN组肺组织W/D(4.7±0.4)与VEN组比较,差异有统计学意义(P＜0.05).VEN组和GLY+VEN组肺组织中IL-1β、IL-6和TNF-α蛋白表达与CON组比较,明显升高(P＜0.05),GLY+VEN组IL-1β和IL-6表达与VEN组比较,表达明显降低(P＜0.05).结论 机械通气前给予格列苯脲可有效减少小鼠肺组织炎症细胞聚集,减轻肺水肿,机制可能与其抑制炎性体的激活有关.     

Effect of the JAK2/STAT3 signaling pathway on epithelial mesenchymal transition of the peritoneum in uremic peritoneal dialysis rats

Objective To investigate whether the JAK2/STAT3 signaling pathway is involved in the epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells in uremic peritoneal dialysis (PD) rats. Methods A total of 48 male Sprague-Dawley (SD) rats were randomly separated into six groups: normal control group (NC group, n=8), sham group (n=8), uremic group (n=8), PD group (n=8), S3I-201 control group (n=8) and S3I-201 group (n=8). Uremic model generated by 5/6 nephrectomy surgery in rats was established. The rats of PD group, S3I-201 control group and S3I-201 group received daily infusion of 4.25% glucose-based peritoneal dialysate fluid (3 ml/100 g) from PD catheters for 28 days. Rats of S3I-201 group were injected with STAT3 inhibitor S3I-201 (2.5 mg/kg) solution from the catheters every other day; the same dose of the solvent of S3I-201 was simultaneously given to S3I-201 control group rats. After PD for 28 days, peritoneal function, pathologic changes, and microvessel density (MVD) were evaluated. Creatinine, urea nitrogen and interleukin-6 (IL-6) concentration in blood and dialysate, and protein and mRNA levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3), E-cadherin, alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) in peritoneum were determined. Results Uremia and peritoneal dialysate could aggravate the peritoneal function and elevate peritoneal thickness and MVD. They could also increased the concentration of IL-6 in blood and dialysate and the expression levels of α-SMA, VEGF, p-JAK2 and p-STAT3 in peritoneum, while lowering E-cadherin expression in peritoneum. These manifestations were even more remarkable in PD group compared to those in uremic group. There was no statistical difference between the S3I-201 control group and the PD group as regards all the index (all P＞0.05). Compared with the S3I-201 control group, the rats treated with S3I-201 showed better peritoneal function. S3I-201 could reduce peritoneal thickness (P＜0.05), MVD (P＜0.05), the concentration of IL-6 in blood and dialysate, the mRNA and protein expression of α-SMA, VEGF, p-JAK2 and p-STAT3 (all P＜0.05), while enhance the mRNA and protein expression of E-cadherin (all P＜0.05). Conclusions After STAT3 is inhibited, the peritoneal thickness, MVD and IL-6 concentration in PD rats are decreased, and EMT is also inhibited, while peritoneal function is improved. The JAK2/STAT3 signaling pathway may thus be involved in the process of EMT of peritoneum in uremic peritoneal dialysis rats by regulating the expression of IL-6.     

The abnormal expressions of tristetraprolin and vascular endothelial growth factor family which participate in ultrafiltration failure

Objective To observe the expression of tristetraprolin (TTP) and vascular endothelial growth factor (VEGF) family, to test and verify whether lymphangiogenesis was involved in the occurrence of ultrafiltration failure (UFF) as well as angiogenesis. Methods Forty male SD rats of clean grade were selected (180-200 g). These rats were divided into five groups randomly: normal group (n=8), sham operation group (n=8), uremia group (n=8), peritoneal dialysis (PD) 2-week group (n=8), PD 4-week group (n=8). The uremic rats model was established by 5/6 nephrectomy, and of which the PD rats model was established on the basis. The rats of PD2-week group and PD4-week group were given regular PD with 4.25% peritoneal dialysis fluid in dose of 3 ml/100 g body weight. PD2-week group received peritoneal dialysis for 2 weeks, PD4-week group for 4 weeks. Before the rats were sacrificed, peritoneal equilibration test (PET) was applied to calculate the mass transfer of glucose and peritoneal ultrafiltration volume. The protein expressions of VEGF, VEGF–C in each group of rats’ parietal peritoneum were detected by immunohistochemical staining. Microvessel density (MVD) and lymphatic vessel density (LVD) of peritoneal tissue were marked and quantified with anti-CD31 antibody, anti-LYVE-1 antibody. RT-PCR was applied to detect the mRNA expressions of VEGF-A, VEGF-B, VEGF-C, VEGF-D, TTP. Western blotting was used to detect the protein expression of TTP. Results (1)PET revealed that, compared with normal group, the mass transport of glucose and the peritoneal ultrafiltration volume of both PD 2-week group and PD 4-week group elevated (P＜0.05); and compared with PD 2-week group, PD 4-week group’s elevated (P＜0.05). (2) Compared with normal group, the protein expression of CD31, LYVE-1, the count of MVD and LVD were increased in uremia group and PD4-week group (P＜0.05). Those of PD4-week groups likewise were increased compared to uremia group (P＜0.05). (3) Compared with normal group, the mRNA expressions of VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D were significantly increased in uremia group (P＜0.05); Compared with uremia group, the expressions in PD4-week group were significantly increased (P＜0.05). Compared with normal group, the mRNA and protein expressions of VEGF, VEGF-C were increased in PD 2-week group (P＜0.05); Compared with PD 2-week group, the expressions were increased in PD 4-week group (P＜0.05). (4) Compared with normal group, the expressions of TTP protein was decreased in uremia group and PD 2-week group (P＜0.05). Compared with uremia and PD2-week group, the expressions of TTP protein was significantly decreased in PD4-week group (P＜0.05). Conclusions High glucose peritoneal dialysis fluid and uremic circumstance result in the expression changes of TTP and VEGF family in a PD time-dependent manner. High glucose peritoneal dialysis liquid gives rise to angiogenesis and lymphangiogenesis, both of which lead to UFF.     

模拟装甲舱室内爆炸后大鼠早期肺损伤研究

目的 观察模拟舱室爆炸伤后肺部损伤特点及炎症早期发展的动态规律.方法 采用模拟舱室、开阔地以600 mg雷管电起爆致伤清醒大鼠,在伤前、后1、3、5、8、12、24、72 h观察肺损伤并检测白细胞介素(IL)-1β,肿瘤坏死因子(TNF)-α水平.结果 舱室与开阔地均压值无差异,但舱室冲击波压力波持续时14.0 ms、峰压力上升时间0.06 ms显著高于开阔地爆炸冲击波(P<0.01);大鼠肺损伤评分及病理特征明显重于开阔地(P<0.01),其中8 h舱室肺伤情评估均值最高为34.33;IL-1β、TNF-α浓度明显升高,且分别在8 h和12 h达到峰值(P<0.01),伤后72 h仍高于对应开阔地血浆浓度.结论 舱室爆炸伤为复杂冲击波,肺伤情较开阔地严重,与IL-1β和TNF-α浓度正相关.     

S-腺苷蛋氨酸对肝脏缺血再灌注损伤大鼠炎症因子的影响

目的：观察S-腺苷蛋氨酸对SD大鼠肝脏缺血再灌注损伤后HIRI炎症因子的影响。方法：将72只SD大鼠随机分为3组：假手术组（Sham组）、缺血再灌注对照组（IR组）、缺血再灌注腺苷蛋氨酸干预组（SAM组）,每组24只。Sham组打开腹腔,游离肝十二指肠韧带,不阻断肝脏血供,20 min后再关腹。IR组和SAM组开腹后游离肝十二指肠韧带,用无创微血管夹夹闭肝蒂,持续20 min后松开血管夹然后关腹。Sham组、IR组术后均予生理盐水1 mL（/kg.d）腹腔注射,SAM组予S-腺苷蛋氨酸100 mg（/kg.d）腹腔注射。3组分别于术后第1、4、7、10天各处死6只大鼠,测定血清和肝组织肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）含量变化,并取肝左叶部分组织行病理组织学观察。结果：SAM组各个时间点血清和肝组织的TNF-α、IL-1β、IL-6水平均明显低于IR组,差别有统计学意义（P〈0.001）;SAM组炎症细胞浸润明显少于IR组。结论：S-腺苷蛋氨酸能够降低HIRI时血清与组织炎症因子水平,减少肝组织炎症细胞浸润,保护肝脏组织。     

ω-3多不饱和脂肪酸对创伤性休克大鼠急性肺损伤的影响

目的 探讨ω-3多不饱和脂肪酸(ω-3 PUFA)对创伤性休克大鼠急性肺损伤的影响.方法 雄性Wistar大鼠36只,体重240～260 g,月龄3月,采用随机数字表法,将大鼠随机分为3组(n=12):对照组(C组);创伤性休克组(TS组)采用骨折复合失血致创伤性休克;ω-3 PUFA组于造模前12 h及2 h经尾静脉注射ω-3 PUFA 2 ml/kg,C组和TS组注射生理盐水2 ml/kg.模型制备成功后120 min时采集颈动脉血样,处死取肺组织.用ELISA法检测血清TNF-α、8-异前列腺素F2α(8-iso-PGF2α)、IL-1β及IL-10的浓度;计算肺组织湿/干重比(W/D比);光镜下观察肺组织病理变化,行病理学评分.结果 与C组比较,TS组和ω-3 PUFA组血清TNF-α、8-iso-PGF2α、IL-1β及IL-10的浓度、肺组织W/D比及病理学评分明显升高(P＜0.01).与TS组比较,ω-3 PUFA组血清TNF-β、8-iso-PGf2α及IL-1β的浓度、肺组织W/D比及病理学评分明显降低,血清IL-10浓度升高(P＜0.05或0.01).结论 ω-3 PUFA可有效地抑制创伤性休克大鼠全身炎性反应,减轻急性肺损伤.

Abstract：

Objective To investigate the effects of ω-3 polyunsaturated fatty acid (ω-3 PUFA) on acute lung injury (ALI) in a rat model of traumatic shock. Methods Thirty-six male Wistar rats aged 3 months were randomly assigned into 3 groups ( n = 12 each): control group (group C) ; traumatic shock group (group TS) and ω-3 PUFA + TS group (group to-3 PUFA) . Traumatic shock was induced by fracture of femur and hemorrhage according to the method described by Feeney in groups TS and ω-3 PUFA. In group ω-3 PUFA, ω-3 PUFA 2 ml/kg was injected via the caudal vein at 12 and 2 h before induction of traumatic shock. Arterial blood samples were taken at 120 min after traumatic shock was successfully induced for determination of serum concentrations of TNF-α, IL-1β, IL-10 and 8-iso-PGF2α by ELISA. The animals were then sacrificed and lungs were removed for-determination of W/D lung weight ratio and microscopic examination. Results Traumatic shock significantly increased serum concentrations of TNF-α, IL-1β, IL-10 and 8-iso-PGF2α, W/D ratio and pathologic scores of lung tissues in groups TS and ω-3 PUFA as compared with group C.ω-3 PUFA significantly attenuated traumatic shuck-induced increase in serum concentrations of TNF-α, IL-1β and 8-iso-PGF2α , W/D ratio and pathologic scores of lung tissues but further increased the serum IL-10 concentration in group ω-3 PUFA as compared with group TS. Conclusion ω-3 PUFA can significantly inhibit the svstemic inflammatory response and ameliorate traumatic shock-induced ALI.     

七氟烷后处理对大鼠肺缺血再灌注损伤的影响

目的 探讨七氟烷后处理对大鼠肺缺血再灌注(IR)损伤的影响及其可能机制.方法 健康SPF级雄性SD大鼠96只,体重270～330 g.随机分为4组(n=24):假手术组(S组)、缺血再灌注组(IR组)、七氟烷预处理组(SPr组)和七氟烷后处理组(SPo组).采用阻断左肺门45 min后再灌注的方法 制备大鼠单肺原位IR模型.SPr组吸入七氟烷,呼气末浓度2.1%,30 min后制备肺IR模型;SPo组于再灌注前即刻吸入七氟烷30 min,呼气末浓度2.1%.分别于再灌注30 min、1、2、4 h时测定支气管肺泡灌洗液(BALF)肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1)、IL-6浓度,并进行白细胞分类计数,计算多形核白细胞占白细胞的百分比(PMN百分比),同时测定肺组织TNF-α、IL-1、IL-6含量及细胞凋亡指数,光镜、电镜下观察肺组织病理学结果 并行损伤评分.结果 与S组比较,IR组肺组织和BALF中TNF-α、IL-1、IL-6水平、细胞凋亡指数、白细胞计数、PMN百分比和肺组织损伤评分均升高,SPr组和SPo组肺组织TNF-α、IL-1、IL-6含量升高(P<0.01);与IR组比较,SPr组和SPo组上述指标均降低(P<0.05或0.01);SPr组与SPo组各指标差异无统计学意义(P>0.05).结论 七氟烷后处理可减轻大鼠肺IR损伤,效果与其预处理无差异,其肺保护作用的机制可能与降低肺组织炎性反应,抑制细胞凋亡有关.     

静脉应用抑肽酶对大鼠肺移植模型缺血再灌注损伤的作用

目的 探讨静脉应用抑肽酶对肺移植后肺缺血再灌注损伤的作用和机制.方法 利用移植肺冷缺血14 h建立的大鼠肺移植缺血再灌注损伤模型,考察抑肽酶对缺血再灌注损伤的影响,并检测细胞因子等指标探讨机制.结果 抑肽酶组较对照组移植肺氧合好、湿干比小,同时支气管肺泡灌洗液中白细胞介素(IL)-2[(113±32)μg/L和(162±43)μg/L,P＜0.05]、血清中IL-8[(7.26±1.01)ng/L和(9.43±0.97)ng/L,P＜0.05]和肿瘤坏死因子(TNF)-α[(152.3±36.4)ng/L和(211.6±52.7)ng/L,P＜0.05]、肺组织中髓过氧化物酶活性[(2.36±0.62)U/g和(3.98±0.36)U/g,P＜0.05]都显著降低.结论 静脉应用抑肽酶能够减轻缺血再灌注损伤,机制可能包括:减少IL-2的释放、抑制TNF-α活化和IL-8产生,抑制中性粒细胞的聚集、激活和脱颗粒.     

可溶性Tie2融合蛋白对尿毒症腹膜透析大鼠血管新生的影响

目的 观察可溶性Tie2融合蛋白(sTie2/Fc)对尿毒症腹膜透析大鼠腹膜血管新生的影响.方法 48只雄性SD大鼠,按随机数字表法分为以下6组:正常对照组、假手术组、尿毒症非腹透组、4.25％腹透组、sTie2/Fc 2.5 μg/kg干预组、sTie2/Fc 5.0 μg/kg干预组.腹透组按照4.25％腹透液30...     

骨髓间充质干细胞移植对吸入性损伤家兔炎症反应和肺损伤的影响

目的 初步了解骨髓间充质干细胞(MSC)移植对烟雾吸入性损伤兔外周血主要炎症因子和肺水质量分数以及肺组织损伤的影响. 方法 取16只成年新西兰大耳白兔制成烟雾吸入性损伤模型后,按随机数字表法分成单纯致伤组和MSC移植组(各8只).单纯致伤组伤后立即经耳缘静脉注入10 mL PBS;MSC移植组伤后立即经耳缘静脉注入10 mL PBS,内含兔第3代MSC(分离自健康幼龄新西兰大耳白兔)1×107个.另取8只成年新西兰大耳白兔作为正常对照组,不致伤,仅经耳缘静脉注入10 mL PBS.单纯致伤组和MSC移植组分别于致伤后2、4、6 h采血,以ELISA法检测血清TNF-α、IL-1β、IL-6、IL-10含量;伤后24 h,取兔肺行大体观察和组织病理学观察(左下肺),取右肺中叶组织计算肺水质量分数.正常对照组同法抽血并取肺组织进行检测.对实验数据行t检验.结果 (1)两致伤组家兔各时相点血清TNF-α含量均明显高于正常对照组(t=2.43～9.57,P＜0.05或P＜0.01).单纯致伤组各时相点血清IL-1β和IL-6含量明显高于正常对照组(t=8.49～19.80,P值均小于0.01);MSC移植组各时相点IL-1β含量与正常对照组接近(t=0.11～0.92,P值均大于0.05),IL-6含量伤后2 h与正常对照组接近(t=2.12,P＞0.05),4、6 h显著升高(t值均为2.83,P值均小于0.05).MSC移植组家兔各时相点血清TNF-α、IL-1β、IL-6明显低于单纯致伤组(t=2.35～12.45,P＜0.05或P＜0.01).(2)MSC移植组伤后2、4、6 h血清IL-10含量分别为(13.0±3.6)、(11.6±8.5)、(15.2±4.4)pg/mL,与单纯致伤组各对应时相点的含量[分别为(5.5±3.4)、(5.0±1.7)、(7.9±3.5)pg/mL]相比均显著升高(t值分别为4.28、2.15、3.67,P值均小于0.01).两致伤组亦明显高于正常对照组(t=2.46～8.14,P＜0.05或P＜0.01).(3)大体观察及组织病理学观察见,MSC移植组肺组织损伤程度较单纯致伤组明显改善.(4)伤后24 h,与正常对照组肺水质量分数(48±3)%相比,两致伤组均明显升高(t值分别为16.93、7.22,P值均小于0.01).MSC移植组肺水质量分数为(69±7)%,较单纯致伤组(87±6)%明显降低(t=5.49,P＜0.01). 结论 MSC移植能降低烟雾吸入性损伤兔外周血促炎因子水平,升高抗炎因子水平,降低肺水质量分数,改善全身炎症反应,对肺组织具有保护作用.     

盐酸戊乙奎醚对内毒素性急性肺损伤大鼠肺组织Toll样受体4mRNA和Toll样受体2mRNA表达的影响

目的 探讨盐酸戊乙奎醚对内毒索性急性肺损伤大鼠肺组织Toll样受体4(TLR4)mRNA和Toll样受体2(TLR2)mRNA表达的影响.方法 健康SD大鼠60只,雌雄不拘,体重200～220g,采用随机数字表法,将大鼠随机分为5组(n=12),对照组(C组)、LPS组和低、中、高剂量盐酸戊乙奎醚组(P1组～P3组).C组腹腔注射生理盐水2ml;LPS组腹腔注射LPS 8mg/kg;P1组～P3组分别腹腔注射LPS 8 mg/kg和盐酸戊乙奎醚0.3、1.0和3.0 mg/kg.给药结束后6 h时开胸,心室取血,并取肺组织,采用ELISA法测定血清TNF-α和Ib-6的浓度,RT-PCR法测定肺组织TLR4 mRNA和TLR2 mRNA 的表达水平,并观察肺组织病理学结果.结果 与C组比较,LPS组、P1组～P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均升高(P<0.05);与LPS组比较,P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05),P1组上述指标差异无统计学意义(P>0.05);与P1组比较,P2组和P1组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05);P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达比较差异无统计学意义(P>0.05).P2组和P3组肺组织病理学损伤程度明显轻于LPS组.结论 盐酸戊乙奎醚可通过下调肺组织TLR4 mRNA和耵JR2 mRNA的表达,降低炎性反应,从而减轻大鼠内毒素性急性肺损伤.

Abstract：

Objective To investigate the effect of penehyclidine (PHCD) on Toll-like receptor 4 (TLR4)mRNA and Toll-like receptor 2 (TLR2) mRNA expression in the lung tissue in rats with acute lung injury induced by lipopolysaccharide (LPS) .Methods Sixty healthy SD rats of both sexes weighing 200-220 g were randomly divided into 5 groups ( n = 12 each) :control group (group C) , LPS group and P1-3 groups. Acute lung injury was induced by intraperitoneal (IP) LPS 8 mg/kg in LPS and P1-3 groups. PHCD 0.3, 1.0 and 3.0 mg/kg were given IP after LPS administration in P1-3 groups. The animals were anesthetized at 6 h after IP LPS. Blood samples were collected for determination of serum TNF-α and IL-6 concentrations ( by ELISA) and then sacrificed, the lungs were immediately removed for determination of TLR4 mRNA and TLR2 mRNA expression (by RT-PCR), and microscopic examination. Results LPS significantly increased TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and IL-6 concentrations. PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS-induced increase in TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and ILr6 concentrations.The lung histopathologic damage was significantly ameliorated in P2 and P3 groups as compared with group LPS.Conclusion PHCD can protect the lungs against LPS-induced acute lung injury through inhibiting TLR4 mRNA and TLR2 mRNA expression in the lung tissue and reducing the inflammatory response.