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目的探讨养肝澳平合剂(YGAPM)对肝纤维化模型大鼠的影响及机制。方法将78只SD大鼠随机分为正常对照组(A组)、肝纤维化模型组(B组)、YGAPM高剂量组(C组)、YGAPM中剂量组(D组)、YGAPM低剂量组(E组)、秋水仙碱组(F组)。B、C、D、E、F组用CCl4/橄榄油腹腔注射法制备肝纤维化大鼠模型,在造模成功后,C、D、E组灌胃不同剂量的YGAPM,F组灌胃秋水仙碱,药物干预8周后采集血清及肝组织。采用生化方法测定大鼠肝功能、超氧化物歧化酶(SOD)、丙二醛(MDA)、羟脯氨酸(HYP)含量。免疫荧光法检测肝组织α-平滑肌肌动蛋白(α-SMA),转化生长因子β1(TGF-β1)。蛋白质印迹法检测TGF-β1、基质金属蛋白酶抑制剂-1(TIMP-1)表达。结果与B组比较,各药物干预组肝功能水平均下降(P<0.01),C组肝功能各指标下降显著(P<0.01),与F组比较,差异亦有统计学意义(P<0.05);药物干预各组肝脏组织MDA、HYP含量明显降低(P<0.01),而SOD含量明显上升(P<0.01),C组较F组有统计学差异(P<0.05,P<0.01)。与A组比较,B组肝组织纤维化面积比例、α-SMA、TGF-β1、TIMP-1表达显著升高(P<0.01),各药物干预组表达均显著下降(P<0.01)。结论 YGAPM能剂量依赖地降低肝脏损伤,改善肝纤维化,机制可能是通过抗炎、抗脂质过氧化从而减少肝细胞损伤,间接降低胶原蛋白含量;并通过直接或间接抑制肝星状细胞(HSC)活化过程中的TGF-β1信号通路,逆转肝纤维化。
Objective To investigate the effect and mechanism of YGAPM on hepatic fibrosis in rats. Methods 78 SD rats were randomly divided into normal control group (group A), liver fibrosis model group (group B), YGAPM high dose group (group C), YGAPM middle dose group (group D), YGAPM low dose group (Group E) and colchicine group (group F). Groups C, D, E and F were treated with intraperitoneal injection of CCl4 / olive oil to establish rat model of hepatic fibrosis. After successful modeling, groups C, D and E were given different doses of YGAPM, Narcissus, serum and liver tissue were collected 8 weeks after drug intervention. The liver function, superoxide dismutase (SOD), malondialdehyde (MDA) and hydroxyproline (HYP) contents were determined by biochemical methods. The expression of α-SMA and TGF-β1 in liver tissues were detected by immunofluorescence. Western blotting was used to detect the expression of TGF-β1 and TIMP-1. Results Compared with group B, the liver function of the intervention group decreased (P <0.01), and the index of liver function decreased significantly in group C (P <0.01), and there was also a significant difference between group B and group F (P <0.05 (P <0.01), while the content of SOD increased significantly (P <0.01). The level of MDA and HYP in group C was significantly lower than that in group F (P <0.05, P <0.01). Compared with group A, the fibrosis area ratio, the expression of α-SMA, TGF-β1, and TIMP-1 in group B were significantly increased (P <0.01), and the expression in each group was significantly decreased (P <0.01). Conclusion YGAPM can reduce liver damage and improve hepatic fibrosis in a dose-dependent manner. The mechanism may be through anti-inflammatory and anti-lipid peroxidation to reduce hepatocellular injury and indirectly reduce collagen content. By directly or indirectly inhibiting hepatic stellate cells ( HSC) activation of TGF-β1 signaling pathway, reversal of liver fibrosis.