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目的:研究谷胱甘肽复方注射液(CGII)对猪血清所致免疫性肝纤维化大鼠肝组织中基质金属蛋白酶-13(MMP-13)以及组织抑制剂-1(TIMP-1)mRNA和蛋白表达的影响。方法:猪血清腹腔注射8周,复制大鼠免疫性肝纤维化模型。将雄性Wistar大鼠随机分为正常组(N组)、模型组(M组)、还原型谷胱甘肽(GSH)组、CGII高(CH,10.8 mg·kg-1)、中(CM,5.4 mg·kg-1)、低(CL,2.7 mg·kg-1)剂量组,第6周末取大鼠肝组织行病理切片,苏木素-伊红(HE)染色,观察病理学改变;用实时荧光定量PCR和Western Blot检测大鼠肝组织中MMP-13以及TIMP-1 mRNA和蛋白的表达。结果:病理结果显示,与模型组相比,CH,CM和CL各组大鼠肝纤维化程度均有明显改善,大鼠肝组织内TIMP-1 mRNA及蛋白水平显著降低,MMP-13 mR-NA和蛋白表达水平明显升高。结论:CGII可明显减轻免疫性大鼠肝纤维化程度,其机制可能与下调TIMP-1 mRNA及蛋白水平,上调MMP-13 mRNA及蛋白水平,改善肝纤维化中MMP-13/TIMP-1的不平衡表达有关。
OBJECTIVE: To investigate the effect of CGII on the expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in the liver tissue of immune-induced hepatic fibrosis in pigs And protein expression. Methods: Porcine serum was injected intraperitoneally for 8 weeks to replicate rat model of autoimmune liver fibrosis. The male Wistar rats were randomly divided into normal group (N group), model group (M group), reduced glutathione (GSH) group, CGII high (CH, 10.8 mg · kg -1) 5.4 mg · kg-1) and low (CL, 2.7 mg · kg-1) groups. At the end of the 6th week, the rat liver tissues were harvested for histopathology and hematoxylin-eosin (HE) staining. The expression of MMP-13 and TIMP-1 mRNA and protein in rat liver tissue were detected by real-time PCR and Western Blot. Results: The pathological results showed that compared with the model group, the levels of liver fibrosis in rats of CH, CM and CL groups were significantly improved, and the levels of TIMP-1 mRNA and protein in the liver tissue of rats were significantly decreased. The expression of MMP- NA and protein expression levels were significantly increased. Conclusion: CGII can significantly reduce the degree of hepatic fibrosis in rats with autoimmune diseases. The mechanism may be related to down-regulating the mRNA and protein level of TIMP-1, up-regulating the mRNA and protein level of MMP-13 and improving the expression of MMP-13 / TIMP- Unbalanced expression.