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缬沙坦对高糖培养系膜细胞信号转导和转录活化因子1、3表达的影响

Effects of valsartan on the expression of STAT1 and STAT3 in glomerular mesangial cells under high concentration of glucose

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【作者】 史永红段惠军王丽晖任韫卓高峰

【Author】 SHI Yong-hong,DUAN Hui-jun,WANG Li-hui,REN Yun-zhuo,GAO Feng(Dept of Pathology,Hebei Medical University,Shijiazhuang 050017,China)

【机构】 河北医科大学病理学教研室河北医科大学病理学教研室 河北石家庄050017河北石家庄050017

【摘要】 目的探讨高糖状态下肾小球系膜细胞中信号转导和转录活化因子1、3的改变以及血管紧张素受体1拮抗剂(AT1Ra)缬沙坦的影响。方法体外培养大鼠肾小球系膜细胞,分别给予高糖和缬沙坦干预,采用W estern印迹检测信号转导和转录活化因子1、3(STAT1、STAT3)及其磷酸化蛋白(p-STAT1、p-STAT3)的表达,酶联免疫吸附实验(ELISA)和放免法测定细胞上清液中TGF-β1、纤维连接蛋白(F ibronectin,FN)和IV型胶原的含量,逆转录-聚合酶链反应(RT-PCR)检测TGF-β1mRNA的表达。结果与低糖对照组相比,高糖组系膜细胞p-STAT1和p-STAT3表达明显上调,TGF-β1、FN和IV型胶原含量增加,TGF-β1mRNA的表达增加。缬沙坦组p-STAT1和p-STAT3的表达明显下调,TGF-β1、FN和IV型胶原的含量减少,同时TGF-β1mRNA的表达降低。结论高糖状态下p-STAT1和p-STAT3表达明显升高,缬沙坦抑制肾小球系膜细胞TGF-β1和细胞外基质的分泌可能部分是通过影响STAT1和STAT3的激活而实现。

【Abstract】 Aim To investigate the effects of valsartan on activation of signal transducers and activators of transcription 1,3 in glomerular mesangial cells(GMCs) under high concentration of glucose.Methods we used high concentration glucose and valsartan to stimulate the cultured rat GMCs in vitro.The protein expressions of signal transducer and activatior of transcription 1,3(STAT1,STAT3),p-STAT1 and p-STAT3 were observed by Western blot.The protein synthesis of TGF-β1,fibronectin and type IV collagen in the supernatants of the GMCs were detected by enzyme-linked immunoadsorbent assay(ELISA) and radioimmunoassay.TGF-β1 mRNA was measured by reverse transcription and polymerase chain reaction(RT-PCR).Results Compared with low glucose control group,the expressions of p-STAT1,p-STAT3 and TGFβ1 mRNA were significantly increased in GMCs under high concentration glucose medium and there observed the high concentration of TGF-β1,fibronectin and type IV collagen in the supernatants.The expression levels of p-STAT1,p-STAT3 and TGF-β1 mRNA were significantly lower in the valsartan group than in those the high concentration glucose group.The concentration of TGF-β1,fibronectin and type IV collagen in the supernatants in the valsartan group were lower than that in the high concentration glucose control group.Conclusion Valsartan can inhibit overproduction of TGF-β1 and ECM proteins in GMCs under high concentration of glucose,partly by regulating the phosphorylation of STAT1 and STAT3.

【基金】 河北省自然科学基金资助项目(NoC2004000536)
  • 【文献出处】 中国药理学通报 ,Chinese Pharmacological Bulletin , 编辑部邮箱 ,2006年02期
  • 【分类号】R965
  • 【被引频次】17
  • 【下载频次】149
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