地龙2号对大鼠肝纤维化TGF-β1,MMP-13及TIMP-1 mRNA和蛋白表达的影响  

Effects of No.2 earthworm extract on expression of TGF-β1, TIMP-1 and MMP-13 in rats with hepatic fibrosis

作　　者：陈洪[1] 陆亚琴 刘顺英[1] 张治国[3] 陈平圣[4] 

机构地区：[1]东南大学附属中大医院消化科,江苏省南京市210009 [2]广州卫生学校内科教研室,广东省广州市510180 [3]南京农业大学生命科学院,江苏省南京市210095 [4]东南大学医学院病理生理学教研室,江苏省南京市210009

出　　处：《世界华人消化杂志》2004年第10期2333-2337,共5页World Chinese Journal of Digestology

基　　金：江苏省中医药管理局科研项目;No.Z-019~~

摘　　要：目的:研究蚯蚓提取物地龙2号对实验性肝纤维化大鼠转化生长因子-β1(TGF-β1),基质金属蛋白酶-13(MMP-13)及基质金属蛋白酶组织抑制物-1(TIMP-1)mRNA和蛋白表达的影响.方法:采用四氯化碳皮下注射诱导大鼠肝纤维化模型.古Wistar大鼠52只随机分成6组:正常组、阴性对照组、模型组、阳性对照组、地龙2号大剂量组和小剂量组;8wk末,用免疫组织化学染色法及RT-PCR检测肝组织中TGF-β1,MMP-13,TIMP-1mRNA和蛋白的表达.结果:地龙2号大、小剂量组肝组织内TGF-β1及TIMP-1mRNA(TGF-β1:0.68±0.16vs0.90±0.29.0.66±0.14vs0.90±0.29,后者P<0.05;TIMP-1:1.01±0.22vs2,48±1.18,1.21±0.38vs2.48±1.18,P<0.01)及蛋白表达均显著低于模型组(TGF-β1:3.14±2.67vs8.22±2.99.3.60±1.90vs8.22±2.99,P<0.01;TIMP-1:3.57±2.23vs7.56±3.40,3.30±2.67vs7.56±3.40,P<0.01),而MMP-13mRNA(1.69±0.75vs0.62±0.21,1.82±0.71vs0.62±0.21,P<0.01)及蛋白表达则明显高于模型组(7.71±1.25vs4.67±2.45,P<0.01,8.50±2.88vs4.67±2.45.P<0.01).结论:地龙2号可下调TGF-β1,TIMP-1mRNA及蛋白的表达,并上调MMP-13mRNA及蛋白的表达,从而抑制或减轻肝纤维化的形成.AIM: To investigate the effects of No.2 Earthworm extract (EE2) on the expression of TGF-β1, TIMP-1 and MMP-13 of in rats with hepatic fibrosis induced by carbon tetrachloride. METHODS: Fifty-two male Wistar rats were randomly divided into 6 groups: normal group (N group, 6 rats), normal control group (NC group, 6 rats), model group (M group, 10 rats), positive control group (PC group, 10 rats), high dose of EE2 group (Eh group, 10 rats) and low dose of EE2 group (El group, 10 rats). The rats in M, PC, Eh and El groups were given the mixture of CCI4 and peanut oil (2 : 3 except the first dose) to induce liver fibrosis, 2 mL/kg sc twice a week. Eh and El groups were also treated with high (0.05 g/kg) and low (0.025 g/kg) doses of EE2, respectively, ig once a day; PC group was treated with colchicine, 0.1 mg/kg ig once a day; M and NC groups were given distilled water, 10 mL/kg ig once a day; and NC group was only administrated with peanut oil, 2 ml/kg sc twice a week. At the end of 8 wk all the survived rats were killed. The expression of mRNA and proteins of TGF-pl, MMP-13 and TIMP-1 were detected by RT-PCR and immunohistochemistry. RESULTS: The levels of mRNA and protein of TGF-β1 and TIMP-1 in liver were significantly reduced in Eh and El groups compared with those in M group (TGF-β1 mRNA: 0.68±0.16vs0.90±0.29, 0.66±0.14 vs0.90±0.29, the latter P <0.05; TIMP-1 mRNA: 1.01±0.22 vs2.48±1.18, 1.21±0.38 vs2.48±1.18, P<0.01. TGF-β1 protein: 3.14 ± 2.67 vs8.22± 2.99, 3.60 ± 1.90 vs8.22 ± 2.99, P<0.01; TTMP-1 protein: 3.57 ± 2.23 vs7.56 ± 3.40, 3.30 ± 2.67 vs 7.56 ± 3.40,P<0.01); while the levels of mRNA and protein of MMP-13 in liver significantly increased in Eh and El groups compared with those in M group (MMP-13 mRNA: 1.69±0.75 vs0.62±0.21,1.82±0.71 vs0.62±0.21, P<0.01; MMP-13 proteins: 7.71 ± 1.25 vs4.67 ± 2.45, P<0.05; 8.50 ± 2.88 vs4.67 ± 2.45,P<0.01). CONCLUSION: EE2 significantly inhibit the development of liver fibrosis in rats induced by CCI4, and its underlying mechanism might re

关 键 词：地龙2号 大鼠 肝纤维化 TGF-Β1 MMP-13 TIMP-1mRNA 蛋白表达 药理 

分 类 号：R285.5[医药卫生—中药学]