还原型谷胱甘肽对胰腺炎相关性腹腔积液诱导的大鼠肝损伤的疗效及其机制

Effect and mechanism of reduced glutathione on liver injury induced by pancreatitis-associated ascitic fluid in rats

目的建立大鼠经腹腔内注射胰腺炎相关性腹腔积液(PAAF)诱导的急性肝损伤模型并研究还原型谷胱甘肽(GSH)对该损伤的疗效及机制。方法先制备急性出血坏死性胰腺炎模型(AHNP)并收集PAAF。A组(对照组)腹腔内注射生理盐水,B组(模型组)腹腔内注射PAAF,C组(GSH治疗组)在向腹腔内注射PAAF前1 h于尾静脉注射GSH。腹腔注射后6 h、12 h分批处死大鼠,每时间点8只。测定大鼠ALT、AST、血清淀粉酶(AmYL)浓度,TBA法检测肝组织丙二醛(MDA)含量,ELISA法检测血清肿瘤坏死因子(TNF-α)、白细胞介素(IL-6),苏木精-伊红染色后光镜观察胰腺及肝损伤情况。结果B组血清ALT、AST、AmYL较同时间段A组升高(P<0.05),血清TNF-α、IL-6浓度及肝组织MDA含量明显升高(P<0.05),B组肝细胞水肿、炎性细胞浸润;C组与同时间段B组相比上述各指标均有降低(P<0.05),肝病理损害较轻。结论GSH通过抗氧自由基、炎症递质的作用减轻PAAF诱导的肝损伤。

Objective To investigate the therapeutic effect of reduced glutathione （GSH） on acute liver injury induced by peritoneal injection of PAAF by establishing the animal injury model in rats and to explore the possible mechanisms underlying the injury and protection. Methods 40 rats were prepared to establish AHNP models. Another 48 rats were randomized into 3 groups （ n = 16） ： group A served as the normal control, with 8 ml normal saline （NS） injected into the peritoneal cavity of the rats; group B as the model control with 8 ml PAAF injected intraperifoneally; group C as the treatment group, with GSH at the dose of 400 mg/kg administrated into the caudal vein 1 h before PAAF injection. At 6 h and 12 h after intraperitoneal injection, the rats were sacrificed in two batches, with 8 rats per batch. The concentration of ALT, AST, AMYL and MDA were measured. Histopathological examination of the liver and pancreas samples were examined with hematoxylin and eosin stain. The levels of IL - 6 and TNF - α in serum were detected by ELISA. Results The levels of ALT, AST, TNF - α were higher than those in group A at during the same period （ P 〈 0. 05 ） , while IL - 6 in the serum and MDA in liver tissue in group B were significantly higher than those in group A （ P 〈 0.05 ）. There was edema in liver cells in group B, with infusion of inflammatory cells. The parameters mentioned above were simultaneously lower in group B compared with those in group C, suggesting the pathological injurywas reduced after GSH administration. Conclusions The animal models of acute liver injury induced by PAAF were successfully established and GSH can reduce the PAAF - induced acute liver injury by resisting the effects of oxygen free radicals and inflammatory mediators.