南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (08): 1232-.

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普伐他汀对P38MAPK信号通路介导的胰岛微血管内皮细胞炎症损伤的保护作用

胡南，孙嘉，康远程，陈建生，罗丽珊，张菊嫦，陈松源，蔡德鸿   

  • 出版日期:2013-08-20 发布日期:2013-08-20

Protective effects of pravastatin against P38MAPK signaling pathway-mediated inflammatory toxicity in islet microendothelial cells

  • Online:2013-08-20 Published:2013-08-20

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摘要： 目的研究脂多糖（LPS）诱导胰岛微血管内皮细胞（IMECs）炎症损伤的相关信号通路及采用普伐他汀干预后的作用机
制。方法以IMECs为实验材料，分为空白对照组、LPS组、SB203580组、普伐他汀组、SB203580+普伐他汀组。以Hoechst凋亡
染色及Annexin V/PI双染色法对不同条件下IMECs的凋亡进行定性定量检测，Western blot法检测总P38MAPK（total-p38）、磷
酸化P38MAPK（p-p38）蛋白及诱导型一氧化氮合酶（iNOS）蛋白的表达水平。结果LPS 组IMECs 较对照组凋亡率升高，
total-p38、p-p38、iNOS蛋白的表达水平上调。与LPS组比较，SB203580组、普伐他汀组与SB203580+普伐他汀组均有凋亡率降
低，total-p38、p-p38、iNOS蛋白表达水平下调。结论LPS诱导的IMECs炎症损伤与P38MAPK及iNOS/NO炎症通路的激活有
关，普伐他汀可阻断以上通路，起到抑制IMECs凋亡、坏死，改善炎症损伤的保护作用。

Abstract: Objective To study the signaling pathways associated with lipopolysaccharide (LPS)-induced inflammation in islet
microendothelial cells (IMECs) and the mechanism of pravastatin intervention. Methods IMECs exposed to LPS, SB203580,
pravastatin, or SB203580 + pravastatin were examined for cell apoptosis with Hoechst staining and flow cytometry and for
expression levels of total-p38, photophosphorylation-p38 (p-p38) and iNOS with Western blotting. Results The apoptosis rate
and expression levels of total-p38, p-p38, iNOS in IMECs all increased after LPS exposure. Pravastatin, SB203580, and their
combination significantly attenuated LPS-induced enhancement of cell apoptosis and total-p38, p-p38, and iNOS expressions
in IMECs. Conclusion LPS-induced inflammatory toxicity in IMECs is associated with the activation of P38MAPK and iNOS/
NO signaling pathways. Pravastatin can inhibit these pathways and suppress the apoptosis and necrosis of IMECs to relieve
the cell inflammatory injuries.