摘要
目的探讨人重组骨形成蛋白-7(rhBMP-7)对高糖诱导的大鼠肾小球系膜细胞转化生长因子-β1(TGF-β1)、结缔组织生长因子(CT-GF)基因表达及细胞外基质(ECM)成分Ⅳ型胶原(ColⅣ)和纤维黏连蛋白(FN)分泌的影响。方法体外培养大鼠肾小球系膜细胞,分为四组:正常对照组(DMEM培养基含1 000 mg/L葡萄糖)、高糖组(DMEM培养基含4 500 mg/L葡萄糖)、rhBMP-7低剂量组(DMEM培养基含4 500 mg/L葡萄糖+50 nmol/L rhBMP-7)、rhBMP-7高剂量组(DMEM培养基含4 500 mg/L葡萄糖+100 nmol/L rhBMP-7)。RT-PCR技术检测TGF-β1和CTGF基因表达水平,ELISA技术检测上清液中TGFβ1、ColⅣ、FN含量。结果 高糖组系膜细胞TGF-β1和CTGF mRNA水平明显高于正常对照组(P<0.01),TGF-β1、ColⅣ和FN分泌增多,与正常对照组比较,差异有统计学意义(P<0.05);与高糖组比较,rhBMP-7不同剂量(50、100 ng/m l)TGF-β1和CTGFmRNA表达明显降低,培养上清中TGF-β1、ColⅣ及FN分泌量亦明显减少,且差异显著(P<0.05)。结论 RhBMP-7通过抑制高糖诱导的大鼠肾小球系膜细胞TGF-β1、CTGF基因表达和ECM的分泌可能起到抗纤维化作用。
Objective To investigate the effect of rhBMP-7 on the expression of transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF) and the extracellular matrix type Ⅳ collagen(Col Ⅳ) and fibronectin(FN) induced by high glucose in rat glomerular mesangial cell.Methods Rat glomerular mesangial cells were cultured in vitro.The cells were divided into 4 groups: control(DMEM containing 1 000 mg/L glucose),high glucose(DMEM containing 4 500 mg/L glucose),rhBMP-7 low(DMEM containing both 4 500 mg/L glucose and 50 ng/ml rhBMP-7) and high(DMEM containing both 4 500 mg/L glucose and 100 ng/ml rhBMP7).TGF-β1 and CTGF mRNA expression were measured by semi-quantitative RT-PCR.Synthesis of TGF-β1,Col Ⅳ and FN in cultured mesangial cells were determined by ELISA.Results High glucose stimulated the upregulation of TGFβ1 and CTGF mRNA and synthesis of TGF-β1,FN and Col Ⅳ,compared with control group(P〈0.05).RhBMP-7 significantly inhibited high glucose mediated upregulation of TGFβ1,CTGF mRNA expression and synthesis of TGF-β1,FN and ColⅣ,compared with high glucose group(P〈0.05).Conclusions RhBMP-7 plays arteriosclerosis role via inhibiting TGF-β1 and CTGF mRNA expression induced by high glucose in rat glomerular mesangial cell,subsequently inhibiting the deposition of FN and Col Ⅳ.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2010年第22期3308-3310,共3页
Chinese Journal of Gerontology
基金
浙江省卫生厅基金(2005B119)