氟伐他汀对转化生长因子β_1诱导的系膜细胞结缔组织生长因子和Ⅳ型胶原表达的影响  被引量:10

Effects of fluvastatin on the expression of connective tissue growth factor and type Ⅳ collagen in mesangial cells induced by transforming growth factor-β1

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作  者:万建新[1] 尤丹瑜[1] 许昌声[1] 

机构地区:[1]福建医科大学附属第一医院肾内科,福建福州350005

出  处:《中国药理学通报》2007年第11期1501-1505,共5页Chinese Pharmacological Bulletin

基  金:福建省教育厅科研基金资助项目(NoJA03102)

摘  要:目的探讨氟伐他汀对转化生长因子β1(TGF-β1)诱导下的大鼠肾小球系膜细胞(MCs)增殖和结缔组织生长因子(CTGF)、Ⅳ型胶原(ColⅣ)表达的影响。方法选择对数生长期的MCs,分成对照组、TGF-β1诱导组、TGF-β1加不同浓度氟伐他汀(Flu)诱导组,采用MTT法检测MCs增殖,RT-PCR和Westernblot方法检测MCsCTGF表达,ELISA法检测ColⅣ表达。结果5μg.L-1TGF-β1能明显促进MCs的增殖及CTGF和ColⅣ的表达。Flu可呈浓度依赖性地抑制TGF-β1诱导下的系膜细胞增殖和CTGF及ColⅣ的表达:1μmol.L-1Flu即能明显抑制MCs的增殖及CTGFmRNA和ColⅣ蛋白的表达,10μmol.L-1Flu即能明显抑制MCsCTGF蛋白的表达。同时,还观察到外源性CTGF呈浓度依赖性地促进MCsColⅣ的表达,2.5μg.L-1CTGF即可明显促进ColⅣ蛋白的表达。结论氟伐他汀可抑制MCs增殖和CTGF介导的ColⅣ表达。Aim To investigate the effects of fluvastatin on the cellular proliferation and the expression of connective tissue growth factor(CTGF)and type Ⅳ collagen(Col Ⅳ)in rat mesangial cells(MCs)induced by transforming growth factor-β1(TGF-β1).Methods MCs are divided into the following groups according to different factors:control group,TGF-β1 group,TGF-β1 plus fluvastatin(Flu,different concentrations)groups.The influence of Flu on rat proliferation of MCs was detected by MTT.The expression of CTGF was measured with RT-PCR and Western blot respectively.The secretion of Col Ⅳ protein was quantitated by ELISA.Results 5 μg·L^-1 TGF-β1 could stimulate proliferation of MCs and the expression of CTGF.Col Ⅳ in MCs significantly.Flu could inhibit proliferation of MCs and the expression of CTGF,Col Ⅳ in MCs induced by TGF-β1 in a dose-dependent manner:1 μmol·L^-1 Flu could suppress proliferation of MCs and downregulate the expression of CTGF,Col Ⅳ significantly,while 10 μmol·L^-1 Flu could just suppress the expression of CTGF protein significantly.Simultaneously exogenous CTGF could promote the expression of Col Ⅳ in a dose-dependent manner:2.5 μg·L^-1 CTGF could just upregulate the expression of Col Ⅳ.Conclusion Fluvastatin could inhibit proliferation of MCs and expression of CTGF-mediated Col Ⅳ in MCs.

关 键 词:氟伐他汀 系膜细胞 增殖 结缔组织生长因子 Ⅳ型胶原 

分 类 号:R-332[医药卫生] R322.61

 

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