扶正化瘀胶囊对瘀血阻络肝肾不足型慢性乙型病毒性肝炎肝纤维化患者外周血单个核细胞中TGF-β1/BMP-7比值的影响

目的观察慢性乙型病毒性肝炎肝纤维化瘀血阻络肝肾不足证型患者在拉米夫定抗病毒的基础上,加用扶正化瘀胶囊抗肝纤维化治疗前后肝功能、乙型肝炎病毒脱氧核糖核酸(hepatitis B virus deoxyribo-nucleicacid,HBVDNA)、肝组织病理学、外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中转化生长因子β1/骨形成蛋白7(transforming growth factor-beta1/bone morphogenetic protein-7,TGF-β1/BMP-7)比值的变化,以及HBVDNA酪氨酸-甲硫氨酸-天门冬氨酸-天门冬氨酸(tyrosine-methionine-aspartate-aspar-tate,YMDD)变异的情况。方法选取瘀血阻络型慢性乙型病毒性肝炎肝纤维化患者80例,分为两组,对照组43例单用拉米夫定治疗,治疗组37例采用拉米夫定加扶正化瘀胶囊治疗,疗程6个月,疗程结束后均继续给予拉米夫定治疗,随访6个月。治疗前后进行肝组织病理检查,采用荧光定量PCR方法测定血清HBV DNA、TGF-β1和BMP-7。随访结束时检测HBV DNA YMDD变异。结果治疗6个月后两组在降低谷丙转氨酶(ALT)、谷草转氨酶(AST)、HBV DNA方面均有很好的疗效,与治疗前比较差异有统计学意义(P<0.05),但组间比较差异无统计学意义。随访6个月发现,对照组有9例出现YMDD变异,治疗组有5例出现YMDD变异,治疗组显著低于对照组(P<0.05)。TGF-β1/BMP-7比值治疗组显著低于对照组(0.09vs0.25,P<0.05)。在肝组织病理学改变方面,治疗组炎症活动度G3以上及纤维化程度S3以上所占比率显著低于对照组(P<0.05)。结论慢性乙型病毒性肝炎肝纤维化瘀血阻络肝肾不足型患者在拉米夫定抗病毒治疗的基础上,加用扶正化瘀胶囊可以降低HBV DNA变异,改善肝组织炎症及纤维化,并可能通过降低TGF-β1/BMP-7比值参与抗肝纤维化。

Effects of Fuzheng Huayu Capsule on the Ratio of TGF-beta1/BMP-7 of Chronic Viral Hepatitis B Fibrosis Patients of Gan-Shen Insufficiency Blood-stasis Obstruction Syndrome

Objective To observe the effects of Fuzheng Huayu Capsule(FHC) on the liver function,HBV DNA quantization,the ratio of transforming growth factor-beta1/bone morphogenetic protein-7(TGF-beta1/BMP-7) of peripheral blood mononuclear cells(PBMCs),HBV DNA YMDD variation,and the liver tissue pathology of chronic viral hepatitis B fibrosis patients of Gan-Shen insufficiency blood-stasis obstruction syndrome(GSIBSOS) on the basis of antiviral treatment by lamivudine.Methods Eighty chronic viral hepatitis B fibrosis patients of GSBSOS were randomly assigned to two groups.Patients in the control group(43 cases) were treated with lamivudine alone,while those in the treatment group(37 cases) were treated with lamivudine + FHC.The treatment period lasted for 6 months.By the end of treatment lamivudine was continually given to all patients,and patients were followed up for 6 months.Before and after treatment,liver tissue pathology was examined by liver biopsy.The serum HBV DNA quantization,the ratio of TGF-beta1/BMP-7 were determined by fluorescence quantitative polymerase chain reaction(PCR).HBV DNA YMDD variation was tested by the end of follow-ups.Results Better effects were obtained in decreasing the levels of ALT,AST,and HBV DNA after 6 months of treatment in the two groups,with statistical difference when compared with before treatment in the same group,but with no statistical difference between the two groups.At the end of the 6th month follow-up,YMDD variation occurred in 9 cases of the control group and in 5 cases of the treatment group,with statistical difference between the two groups(P<0.05).FHC could significantly reduce the ratio of TGF-beta1/BMP-7,significantly lower in the treatment group(0.09 vs 0.25,P<0.05).In the aspect of liver tissue pathological changes,the rates of inflammatory activity over G3 and fibrosis degree S3 in the treatment group were significantly lower than those in the control group(P<0.05).Conclusions On the basis antiviral treatment of lamivudine for chronic viral hepatitis B fibrosis patients of BSOS,additional application of FHC could lower the HBV DNA YMDD variation,improve the hepatic inflammation and fibrosis,and exert anti-fibrosis by decreasing the ratio of TGF-beta1/BMP-7.