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目的:观察黄连素(Berberine,BBR)是否能够通过活化胆汁酸膜受体TGR5,从而抑制高糖引起的纤维连接蛋白FN的表达升高以及核因子AP-1的激活,改善由高糖引起的肾小球系膜细胞(GMCs)纤维化的发生。方法:采用小分子RNA干扰肾小球系膜细胞TGR5的蛋白表达,Western blot检测肾小球系膜细胞中TGR5、FN、ICAM-1、TGF-β1、p-c-Jun ser63、p-c-Jun ser73以及pc-Fos ser32蛋白水平。结果:30μmol/L黄连素能够明显抑制高糖培养的肾小球系膜细胞炎症因子(ICAM-1)和转化生长因子(TGF-β1)的表达,细胞外基质主要成分纤维连接蛋白(FN)生成明显减少。同样,给予黄连素处理后,能抑制HG诱导的c-Jun/cFos磷酸化水平。TGR5特异性激动剂INT-777能够剂量依赖性抑制高糖引起的FN、ICAM-1以及TGF-β1上调,并且10μmol/L的浓度下其抑制作用即具有显著性意义。而在干扰TGR5表达后,30μmol/L黄连素抑制高糖引起的FN、ICAM-1以及TGF-β1的作用被取消。结论:激活TGR5,抑制AP-1的活性可能是黄连素抑制高糖引起的FN、ICAM-1以及TGF-β1上调的分子机制之一。
AIM: To investigate whether berberine (BBR) can activate the bile acid receptor TGR5 and thus inhibit the high glucose induced fibronectin FN expression and nuclear factor AP-1 activation, The occurrence of glomerular mesangial cells (GMCs) fibrosis. Methods: The protein expression of TGR5 in mesangial cells was detected by small RNA interference. The expressions of TGR5, FN, ICAM-1, TGF-β1, pc-Jun ser63 and pc-Jun ser73 in glomerular mesangial cells pc-Fos ser32 protein level. RESULTS: Berberine (30μmol / L) significantly inhibited the expression of ICAM-1 and TGF-β1 in high glucose and fibronectin (FN) Generate a significant reduction. Similarly, administration of berberine inhibited HG-induced c-Jun / cFos phosphorylation. INT-777, a specific agonist of TGR5, can up-regulate FN, ICAM-1 and TGF-β1 induced by high glucose in a dose-dependent manner, and its inhibitory effect is significant at a concentration of 10μmol / L. However, the effect of 30μmol / L berberine on inhibiting FN, ICAM-1 and TGF-β1 induced by high glucose was abolished after interfering with the expression of TGR5. Conclusion: Activation of TGR5 and inhibition of AP-1 activity may be one of the molecular mechanisms by which berberine inhibits the up-regulation of FN, ICAM-1 and TGF-β1 induced by high glucose.