化橘红有效成分柚皮苷对高糖诱导CMECs凋亡的抑制作用

Inhibition of Pummelo Peel active ingredient Naringin on high glucose-induced CMECs apoptosis

目的 观察化橘红有效成分柚皮苷（Naringin）对高糖诱导心肌微血管内皮细胞（CMECs）凋亡的影响,探讨Naringin对CMECs损伤的保护作用及可能的机制.方法 CMECs系分为正常糖组、高糖组、高糖＋Naringin （50、100、200 μmol/L）处理组.Western印迹法检测CMECs p38丝裂原激活蛋白激酶（MAPK）（p38）、凋亡相关蛋白Caspase9的表达及其活性;荧光探针JC-1观察线粒体膜电位.结果 ①高糖刺激CMECs p38 MAPK信号通路的激活,p38蛋白表达明显上调,正常糖对照组仅有少量p38蛋白表达;高糖＋Naringin（50、100、200μg/ml）组p38蛋白表达量较高糖组明显下降（P＜0.05）.②高糖培养诱导CMECs48h后可见Caspase9的表达及其活性明显增加,与正常糖组比较差异有统计学意义（P＜0.05）,相应CMECs线粒体膜电位降低;naringin（50、100、200 μmol/L）预处理CMECs,明显抑制高糖诱导的CMECs Caspase 9表达及其活性,差异均有统计学意义（P＜0.05）,抑制率分别是50％、64％、68％和54％、65％、68％;CMECs线粒体膜电位也不同程度降低.结论 化橘红有效成分Naringin（50、100、200 μmol/L）能够减少高糖诱导的CMECs凋亡,可能与其抑制p38 MAPK活化相关,并呈一定浓度依赖性.

Objective To explore the therapeutic effects of Pummelo Peel active ingredient Naringin on high glucose-induced cardiac microvascular endothelial cells （CMECs） injury and understand its mechanism.Methods The CMECs system were divided into normal glucose group （NG）,high glucose group （HG） and HG with Naringin at high,medium and low dose （50,100,200 μmol/L） group.The expression of p38MAPK and the expression and activity of Caspase 9 were determined by Western blot mitochondrial membrane potential was detected by Fluorescence probe JC-1.Results （1）CMECs with high glucose could activate the p38 MAPK signaling pathway.The expression of p38MAPK was significantly elevated.Little expression of p38MAPK was observed in NG.As compared to HG,the expression of p38MAPK was significantly lowered in Naringin groups.（2）The expression and activity of Caspase 9 increased in HG with upregulated mitochondrial membrane potential after 48 h.It was significantly higher than those in NG.Naringin（50,100,200 μmol/L） could reduce the CMECs Caspase 9 induced by high glucose 50％,64％,68％ and 54％,65％,68％ respectively,and downregulated mitochondrial membrane potential.Conclusion Naringin can inhibit high glucose-induced CMECs apoptosis.And this effect may be involved in its inhibition of activation of p38MAPk,and a certain concentration dependence.