短链脂肪酸对高糖诱导的肾系膜细胞氧化应激-炎症的影响

Effects of short-chain fatty adds on oxidative stress and inflammation in glomerular mesangial cells induced by high glucose

探讨外源性短链脂肪酸（SCFAs）对高糖诱导的肾系膜细胞氧化应激-炎症的影响。体外培养正常小鼠肾系膜细胞，高糖作为刺激因子，设计siRNA靶向沉默SCFAs特异性G蛋白耦联受体43（GPR43）表达，观察不同浓度SCFAs（乙酸、丙酸、丁酸）和GPR43受体激动剂干预后细胞活性氧簇、丙二醛和炎症因子单核细胞趋化蛋白1（MCP-1）、白细胞介素1β（IL-1β）表达的变化。SCFAs和GPR43受体激动剂呈浓度依赖性抑制高糖诱导的肾系膜细胞活性氧簇和丙二醛生成，抑制MCP-1和IL-1β的表达和释放（均P〈0.05）；SiRNA靶向沉默GPR43受体部分逆转SCFAs介导的抗氧化应激和抗炎效果（均P〈0.05）。外源性SCFAs抑制高糖诱导的肾系膜细胞氧化应激及炎症损伤，其机制可能与GPR43受体介导的信号通路有关，该信号通路可能是糖尿病肾脏疾病的潜在防治靶点。

To investigate the effects of short-chain fatty acids（SCFAs）on oxidative stress and inflammation in cultured glomerular mesangial cells（GMCs）under high glucose. SV-40 MES 13 mouse GMCs were exposed to 30 mmol/L glucose, exogenous SCFAs or their specific G-protein coupled receptor 43（GPR43）agonist were used individually as an intervention. GPR43 expression was suppressed by transfection with GPR43-specifc siRNA. The oxidative stress-related factors reactive oxygen species and malondialdehyde were detected and the expression of GPR43, monocyte chemotactic protein 1（MCP-1）, and interleukin-1β（IL-1β）were observed. GPR43 expression were significantly down-regulated, but reactive oxygen species and malondialdehyde production and MCP-1 and IL-1β releases were induced by high glucose（all P〈0.05）, treatment with SCFAs or GPR43 agonist reversed high glucose-induced oxidative stress and inflammation in a dose-dependent manner（all P〈0.05）. However, these SCFAs-mediated effects were blunted by siRNA-mediated knockdown GPR43（all P〈0.05）. SCFAs mitigates high glucose-induced oxidative stress and inflammatory injury in part via GPR43 signaling pathway, suggesting a likely mechanism for SCFAs-induced therapeutic effect in diabetic kidney disease. （Chin J Endocrinol Metab, 2018, 34： 239-245）