从“五脏相关”理论探讨肝脾肾同治法抗大鼠免疫损伤性肝纤维化的机制

Mechanism Investigation of Liver,Spleen and Kidney Synergistic Treatment of Hepatic Fibrosis Induced by Immune Injury in Rats According to the Theory of“Correlation between Five Viscera”

目的从"五脏相关"理论探讨肝脾肾同治法对大鼠免疫损伤性肝纤维化核转录因子-κB(NF-κB) p65、肿瘤坏死因子-α(TNF-α)、α-平滑肌肌动蛋白(α-SMA)、金属蛋白酶组织抑制-1(TIMP-1)mRNA表达的影响。方法将48只SD大鼠随机分作4组:正常组,模型组,肝脾肾同治组,鳖甲煎丸组,每组12只。猪血清腹腔注射法建立肝纤维化大鼠模型,治疗结束后检测大鼠肝组织TNF-α、NF-κB p65、α-SMA、TIMP-1 mRNA表达情况。结果肝纤维化模型组Metavir病理分期、NF-κB p65、TNF-α、α-SMA、TIMP-1 mRNA表达显著高于正常组(P<0.01)。与模型组比较,肝脾肾同治法能显著改善肝纤维化病理,减少肝组织NF-κB p65、TNF-α、α-SMA及TIMP-1 mRNA的过表达(P<0.01)。结论肝脾肾同治法有可能通过抑制NF-κB信号通路,减轻肝细胞周围的炎症微环境,促进活化的肝星状细胞凋亡,从而发挥抗纤维化作用。

Objective:To investigate the effect of synergistic treatment of liver,spleen and kidney(STLSK)therapy on the expression of NF-κB p65,TNF-α,α-SMA and TIMP-1 mRNA in rats with hepatic fibrosis induced by immune injury according to the theory of"Correlation between Five Viscera".Methods:48 SD rats were randomly divided into 4 groups:normal group,model group,STLSK group and Biejiajian Pills group,12 rats in each group.The rat model of hepatic fibrosis was established by intraperitoneal injection of pig serum.The expressions of TNF-α,NF-κB p65,α-SMA,TIMP-1 m RNA in rats liver tissues were detected after treatment.Results:The expressions of Metavir pathological staging,NF-κB p65,TNF-α,α-SMA and TIMP1 mRNA in model group were significantly higher than those of the normal group(P<0.01).Compared with the model group,STLSK group can significantly improve the pathology of liver fibrosis and reduce the overexpression of NF-κBp65,TNF-α,α-SMA and TIMP-1 mRNA in liver tissues(P<0.01).Conclusion:It is possible that STLSK therapy may play an anti-fibrosis role by alleviate inflammatory microenvironment around hepatocytes and promote apoptosis of activated hepatic stellate cells by inhibiting NF-κB signaling pathway.