ConA诱导肝细胞损伤机理及CsA对其损伤的影响

Mechanisms of hepatic injury induced by conA and role of CsA on the hepatic injury

目的 探讨NO、脂质过氧化反应及蛋白巯基状态改变在ConA诱导肝组织细胞损伤过程中的作用以及CsA对其损伤的影响。方法 :尾静脉注射ConA( 2 0mg·kg-1)于雄性BALB/c小鼠作为试验组 ;提前半小时予以CsA( 2 5mg·kg-1)后再按试验组处理作为CsA组。观察血清中ALT、AST、NO-2 及肝组织MDA、TSH、PSH含量在 3h、6h、9h和 12h的动态变化。结果 试验组血清中ALT、AST进行性升高 ,在 12h时与对照组、CsA组比较均P <0 .0 1。试验组动物体内有大量的NO合成 ,血清中NO-2 随时间呈明显上升趋势 ,在 12h时与对照组、CsA组比较均P <0 .0 1。试验组动物肝组织MDA含量逐步升高 ,在 12h与对照组、CsA组比较P <0 .0 1。试验组动物肝组织TSH含量不断下降在 12h与对照组、CsA组比较P <0 .0 5 ;PSH含量亦不断下降在 12h与对照组、CsA组比较P <0 .0 1。对照组和CsA组血清中ALT、AST及NO-2 前后变化不大 ,肝组织MDA、TSH、PSH含量变化亦不明显。结论 在ConA所致肝损伤中 ,动物体内NO生物合成机制被激活 ,是肝细胞损伤的重要介质之一。同时脂质过氧化的发生以及蛋白巯基持续消耗致肝组织细胞的抗氧化能力和解毒能力下降也均是ConA性肝损伤机制之一。免疫抑制剂CsA预处理能阻断ConA性肝损伤的发生 ,免疫介导机制亦可能是其损伤?

Objective To Study effects of NO(Nitrogen monoxide), LP(lipid peroxidation), sulfhydryl and role of CsA(Cyclosprin A) on hepatic injury induced by ConA (Concanavalin A). Method In the experiments, 84 BALB/c male mice were randomly divided into three groups. NS (normal saline, 0.2 mL) was injected intraperitoneally to be regarded as the control group. ConA(Concanavalin A, 20mg·kg^(-1)) in NS was injected intraperitoneally to be served as the test group. CsA (25 mg·kg^(-1)) was administrated at half an hour before ConA management to be served as the CsA group. Plasma samples for ALT, AST, NO^-_2 measurements were obtained at 3,6,9 and 12h after respective treatments in each group, meanwhile contents of MDA(malondialdehyde), TSH(total sulfhydryl), PSH(protein-bound sulfhydryl) of in liver tissue homogenate were detected. Result In the test group, the level of ALT, AST, NO^-_2 in plasma ascending sharply(P<0.01,vs the control group and the CsA group respectively at 12h). Contents of MDA in liver tissue homogenate of the test group increased continuously(P<0.01,vs the rest groups respectively at 12h). Contents of TSH in liver tissue homogenate of the test group decreased gradually (P<0.05,vs the rest groups respectively at 12h), and PSH decreased, too (P<0.01,vs the rest groups respectively at 12h). There was little change of ALT, AST, NO^-_2 in plasma and MDA, TSH,PSH in liver tissue homogenate in the rest groups. Conlusion The biosynthetic mechanism of NO is triggered, and NO plays an important role in the hepatic injury induced by ConA. LP and lasting consumption of PSH might involve in the mechanism of the liver injury. CsA has potential effect on the protection of the liver injury, indicating that immunologic reaction is one of mechanisms of liver injury induced by ConA.