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目的探讨沉默信息调节因子1(SIRT1)对高糖诱导的系膜细胞内皮素-1(ET-1)和转化生长因子β1(TGF-β1)的影响。方法体外培养系膜细胞分为:(1)高糖组(高糖培养液);(2)SIRT1激动剂(白藜芦醇)+高糖组,含1μmol/L白藜芦醇的高糖培养液;(3)SIRT1 RNAi干扰+高糖组,加入pTRC-shSIRT1慢病毒感染;(4)正常对照(NC)组。检测各组细胞SIRT1基因表达,以及ET-1和TGF-β1水平。结果高糖组、SIRT1激动剂+高糖组、SIRT1RNAi干扰+高糖组及NC组ET-1含量分别为(56.1±6.3)、(31.9±5.1)、(105.63±8.2)和(17.3±3.4)pg/ml;TGF-β1含量分别为(43.3±5.7)、(27.5±4.9)、(87.4±7.3)和(15.6±3.6)ng/ml。高糖抑制SIRT1表达,上调ET-1和TGF-β1表达(P<0.05);SIRT1激动剂可改善高糖对SIRT1的抑制,下调ET-1和TGF-β1表达(P<0.05);沉默SIRT1,可上调ET-1和TGF-β1表达(P<0.05)。结论 SIRT1基因对高糖诱导的系膜细胞ET-1和TGF-β1可能起负调控作用。
Objective To investigate the effect of SIRT1 on the expression of endothelin-1 (ET-1) and transforming growth factor-β1 (TGF-β1) induced by high glucose in mesangial cells. Methods Mesangial cells cultured in vitro were divided into: (1) high glucose group (high glucose medium); (2) SIRT1 agonist (resveratrol) + high glucose group, high glucose containing 1μmol / L resveratrol (3) SIRT1 RNAi interference + high glucose group, adding pTRC-shSIRT1 lentivirus infection; (4) normal control (NC) group. The SIRT1 gene expression and the levels of ET-1 and TGF-β1 in each group were detected. Results The levels of ET-1 in high glucose group, SIRT1 agonist + high glucose group, SIRT1RNAi interference + high glucose group and NC group were (56.1 ± 6.3), (31.9 ± 5.1), (105.63 ± 8.2) and (17.3 ± 3.4 ) pg / ml; TGF-β1 contents were (43.3 ± 5.7), (27.5 ± 4.9), (87.4 ± 7.3) and (15.6 ± 3.6) ng / ml respectively. High glucose could inhibit the expression of SIRT1 and up-regulate the expression of ET-1 and TGF-β1 (P <0.05). SIRT1 agonist could improve the inhibition of SIRT1 by high glucose and down-regulate the expression of ET-1 and TGF- , Up-regulated the expression of ET-1 and TGF-β1 (P <0.05). Conclusion SIRT1 gene may play a negative regulatory role on high glucose-induced mesangial cells ET-1 and TGF-β1.