外源性IL-33在体外模拟糖尿病条件下抑制心肌成纤维细胞胶原蛋白的表达

Effects and mechanism of exogenous IL-33 on cardiac fibroblast collagen expression under diabetic condition in vitro

目的:探索体外模拟糖尿病状态下外源性IL-33对心肌成纤维细胞的作用。方法:体外分离培养新生乳鼠心脏成纤维细胞,设立对照组(DMEM/F12+30 mmol/L甘露醇),高糖组(DMEM/F12+30 mmol/L葡萄糖),高糖+高迁移率族蛋白1(HMGB1)组(1μg/m L),高糖+HMGB1+IL-33组(3 ng/m L)。经不同处理后,蛋白质印迹检测胶原蛋白Ⅰ、IL-33、二酰基甘油激酶ζ(DGKζ)表达量的变化;ELISA检测二酰基甘油(DAG)的分泌释放,以及蛋白激酶Cβ(PKCβ)活性的改变。结果:心肌成纤维细胞经高糖处理后胶原蛋白Ⅰ生成增加,IL-33产量降低,HMGB1使上述情况进一步加剧,心肌细胞内DGKζ的表达下调,引起DAG的升高,并进一步促进PKCβ的激活,引发心肌纤维化。加入外源性IL-33对上述过程具有抑制作用,可抗心肌纤维化。结论:外源性IL-33在心肌成纤维细胞模拟糖尿病状态下起抗纤维化作用。

Objective：To investigate the role of IL-33 on cardiac fibrosis under high glucose treatment on cardiac fibroblasts.Methods：Isolated rat cardiac fibroblasts were divided into following groups：control （DMEM/F1 2＋30 mmol/L mannitol）,high glucose（DMEM/F1 2 ＋30 mmol/L glucose）,high glucose ＋HMGB1 （1 μg/mL）,high glucose ＋HMGB1 ＋IL-33 （3 ng/mL）.The expression of the collagen I,IL-33 and DGKζin the cardiac fibroblasts were evaluated by western blotting.The DAG and the activity of PKCβwas detected by ELISA.Results：When cardiac fibroblasts challenged with high glucose,the collagen I gen-eration was increased and the production of IL-33 was decreased.The effect of high glucose was exaggerated by HMGB1 .In addition,the DGKζexpression was decreased,DAG content was increased and further pro-moted the activation of PKCβ.Exogenous IL-33 attenuated above effects.Conclusion：Exogenous IL-33 plays a key role in anti-cardiac fibrosis induced by high glucose.