【摘要】 目的探讨TGF-β1、TIMP-1、MMP-1在HBeAg阴性CHB患者肝纤维化诊断中的作用以及抗乙肝病毒治疗对其影响。方法以正常体检健康者为对照组,HBeAg阴性CHB分轻度、中度、重度组,依据抗病毒治疗48周后HBV DNA低于检测下限分为治疗有效组和治疗无效组,ELISA法测定各组血清中TGF-β1、TIMP-1、MMP-1含量,免疫组化检测肝组织TIMP-1、MMP-1表达。结果HBeAg阴性慢性乙型肝炎外周血TGF-β1、TIMP-1水平明显高于正常对照组(P<0.01),而血清MMP-1则明显低于正常对照组(P<0.01)。随慢性肝炎轻度-重度逐渐发展,血清TGF-β1、TIMP-1的水平逐渐增高,且差异有统计学意义(P<0.05)。TIMP-1蛋白在肝纤维化组织的阳性表达,随肝纤维化程度的加重而增强,呈正相关(rs=0.618,P=0.002);MMP-1蛋白在肝纤维化组织的阳性表达与肝纤维化程度无相关性(rs=0.077,P=0.732)。抗病毒治疗48周后有效组血清TGF-β1、TIMP-1的含量明显下降,MMP-1水平上升(P<0.01)。无效组血清TGF-β1、TIMP-1、MMP-1水平变化不明显(P>0.05)。结论联合检测TGF-β1、TIMP-1、MMP-1是判断慢性肝病患者有无纤维组织增生敏感而可靠的指标,动态观察上述指标的变化,对临床判断肝纤维化程度和活动度有着重要价值,同时也为临床疗效的判断提供有效的实验依据。更多还原

【Abstract】 Objective To detect the expressions of transforming growth factor-beta(TGF-β1),tissue inhibitors of metalloproteinase-1(TIMP-1) and matrix metalloproteinase-1(MMP-1) in HBeAg-negative chronic hepatitis B patients and to investigate the effects of TGF-β1,TIMP-1,and MMP-1 on the diagnosis of hepatic fibrosis as well as anti-hepatitis B virus treatment influence on them.Methods Normal health examinations were as controls,HBeAg-negative chronic hepatitis B patients were divided into the mild group,moderate group and severe group.According to the serum HBV-DNA levels at week 48,HBeAg-negative chronic hepatitis B patients were divided into the effective group and the ineffective group.The serum levels of TGF-β1,TIMP-1 and MMP-1 were detected by ELISA.Positive rate and degree of staining about the expressions of TIMP-1 and MMP-1 in liver fibrosis tissue were detected by immunohistochemistry.Results The serum levels of TGF-β1 and TIMP-1 in the HBeAg-negative chronic hepatitis B groups(P<0.01),the level of serum MMP-1 in the HBeAg-negative chronic hepatitis B patients were lower than those in the control group(P<0.01).With the degree of liver inflammation increasing,the expressions of TGF-β1,TIMP-1 significantly were increased(P<0.05).The expression of TIMP-1 protein in the liver tissues was positively correlated with liver fibrosis staging(rs=0.618,P=0.002);the expression of MMP-1 protein in the liver tissues showed no significant correlation with liver fibrosis staging(rs =0.077,P=0.732).Compared with before treatment,the serum levels of TGF-β1 and TIMP-1 were markedly decreased in effective group(P<0.01),the serum levels of MMP-1 was increased(P<0.01),but there was no obviously changes in the ineffective group(P>0.05).Conclusion The serum levels of TGF-β1,TIMP-1 and MMP-1 were correlated with severity of chronic hepatitis,they are useful indices to diagnose liver fibrosis and evaluate the response to antiviral therapy.更多还原