坎地沙坦在炎症过程中抑制氧化应激反应机制的研究

The mechanism of anti-inflammation effects by candesartan during inflammation

目的探讨坎地沙坦(Cand esartan,CAN)是否具有不依赖血管紧张素1型受体(anti-inflammation viaindependent,AT1R)的抗炎作用及其可能的机制。方法以人肾小管上皮细胞为研究对象,观察CAN对肿瘤坏死因子(TNF-α)诱导炎症趋化因子的影响及CAN对TNF-α所诱导ROS的作用。采用RT-PCR方法测定相关分子mRNA表达,Western blotting和ELISA方法测定相关分子蛋白含量。结果 CAN能有效抑制TNF-α诱导炎症趋化因子MCP-1、RANTES mRNA和蛋白表达,且能抑制TNF-α诱导的NF-αB磷酸化。CAN还具有类是抗氧化应激物N乙酰半胱氨酸(NCA)的作用,抑制TNF-α诱导的ROS产生。结论 CAN能抑制TNF-α诱导肾小管上皮细胞发生炎症反应,其机制与CAN的直接抗氧化作用有关。

Objective To study the role of Candesartan （CAN） in anti-inflammation via independent of AT1R pathway and its mechanism. Methods Renal tubular epithelial cells were stimulated by TNF-α. The effects of CAN on inflammatory chemokines and ROS synthesis in the cells induced by TNF-α were observed. The expression level of mRNA was detected by RT-PCR, and the levels of proteins were detected by Western blotting and ELISA. Results CAN suppressed mRNA and protein expressions of pro-inflammatory chemokines MCP-1 and RANTES in human proximal epithelial cells induced by TNF-α with a dose dependent fashion. CAN also inhibited TNF-α-induced NF-KB phosphorylation in the cells. CAN likes N-acetyl cysteine （NAC）, a reactive oxygen species （ROS） scavenger, blocked TNF-α and H202-induced ROS generation. Conclusion CAN can suppress infl＋ ammatory reponsiveness in the cell induced by TNF-α. The mechanism of the effect maybe associate with its direct anti-ROS generation.