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肝细胞增殖、凋亡与肝纤维化关系的实验研究 被引量:19

Relationship between hepatocyte proliferation,apoptosis and advancing of liver fibrosis
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摘要 目的动态观察实验性肝纤维化大鼠肝细胞增殖、凋亡情况,探讨肝细胞增殖、凋亡与肝纤维化进展的关系。方法Wistar大鼠分为正常、对照组和肝纤维化模型组,HE染色观察肝组织形态学变化,赖氏法检测ALT、AST,竞争性放射免疫分析法测定透明质酸、Ⅳ型胶原,免疫组化方法检测PCNA(增殖细胞核抗原)的表达,TUNEL标记法检测肝细胞凋亡百分率。结果(1)病理形态学分析和血清检测结果:造模5周末模型组可见肝小叶结构紊乱,汇管区扩大,纤维组织增生,8周末有明显完整的纤维间隔包绕肝结节形成假小叶;造模5周及8周末,模型组血清ALT、AST、透明质酸、Ⅳ型胶原较正常组明显增高,差异有统计学意义(P<0.01)。(2)肝细胞增殖率测定(PCNA):造模5周及8周末,模型组大鼠肝细胞增殖明显多于正常组(P<0.01),模型组造模5周与8周相比,差异有统计学意义(P<0.05)。(3)肝细胞凋亡率测定(TUNEL法):造模5周及8周末,模型组大鼠肝细胞凋亡明显多于正常组(P<0.01)。结论肝纤维化时肝细胞凋亡较正常对照组增加,提示肝细胞凋亡是肝细胞增生不良、肝纤维化进展的重要促动因素。 Objective To investigate the relationship between hepatocyte proliferation,apoptosis and advancing of liver fibrosis by dynamical observation of hepatocyte proliferation and apoptosis in liver fibrosis. Methods Rats were randomly divided into two groups:the normal control group and the model group. Murine sera were collected for the measurement of ALT, AST, HA, Ⅳ-c. Excised liver tissues were fixed with 4% formaldehyde for HE staining. Immunohistochemistry was performed to determine the protein of PCNA. In addition , TUNEL method was used to study hepatocyte apoptosis. Results (1)Pathomorphometrical analysis and serum content analysis:in the model group on 5,8 week, many fibrous tissues formed and extended into the hepatic lobules to separate them and there was a higher level of ALT, AST, HA, Ⅳ-c compared with the normal control group (P〈0.01). (2)PCNA positive ratio analysis: compared with the normal control group, there was an increased expression of PCNA in the model group at the end of 5,8 week (P〈0. 01). Compared with the model group at the end of 5 week, PCNA positive ratio was decreased in the model group at the end of 8 week (P〈0.05). (3) Apoptotic rate analysis., compared with the normal control group, there were more apoptosis hepatocytes in the model group at the end of 5,8 week (P〈0.01). Conclusion Apoptosis of hepatocyte was increased compared with the normal control group in liver fibrosis. A large number of apoptosis of hepatocytes result in the badness of hepatoeyte proliferation. Apoptosis of hepatocytes is the important promoter of liver fibrosis.
作者 周伟 沈薇
出处 《重庆医学》 CAS CSCD 2007年第11期1062-1064,共3页 Chongqing medicine
关键词 肝纤维化 增殖 凋亡 liver fibrosis proliferation apoptosis
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