内质网应激在百草枯上调缺氧诱导因子1α中的作用

The role of endoplasmic reticulum stress in parquat-induced hypoxia-inducible factor 1α up-regulation

目的:探讨内质网应激在百草枯(PQ)上调缺氧诱导因子1α(HIF-1α)中的作用。方法:将60只雄性SD大鼠按照随机数字表法分为对照组(10只)和染毒组(50只),染毒组按照50mg/kg的标准将20%的PQ用生理盐水稀释到1ml进行一次性灌胃,于灌胃后2、6、12、24、48h处死动物取肺组织。提取肺组织总蛋白,采用Western Blotting检测HIF-1α和内质网应激标志物GRP78、XBP1的表达。选择ERS抑制剂4-苯基丁酸进行预处理,再施以PQ暴露,Western Blot和免疫荧光检测肺组织中GRP78及HIF-1α的表达。结果:染毒后2h肺组织中HIF-1α、GRP78和XBP1蛋白表达均较对照组明显升高,随时间延长,逐步增高。采用4-苯基丁酸抑制处理后,与PQ处理组比较,大鼠肺组织中GRP78、HIF-1α表达减少。结论:PQ进入肺组织后,可能通过诱导ERS上调HIF-1α的表达参与肺纤维化。

Objective：To investigate the role of endoplasmic reticulum stress in paraquat-induced hypoxia-inducible factor 1αup-regulation.Method：60healthy Sprague-Dawley rats were randomly divided into control group（n=10）and paraquat poisoning group（n=50）.The control group was treated with saline,and the paraquat poisoning group were received intragastric infusion of 20 % paraquat solution（50mg·kg^-1）.Rats of paraquat poisoning group were subsequently divided into five subgroups（n=10）and lung tissues were collected at 2h,6h,12 h,24 h,48 hafter paraquat poisoning.HIF-1αand endoplasmic reticulum stress markers,including GRP78,XBP1 were measured by Western Blot.After treating with an endoplasmic reticulum stress inhibitor 4-Phenybutyric acid,we then measured the expression of GRP78 and HIF-1αby Western Blot and immunofluorescence.Result：HIF-1αand endoplasmic reticulum stress markers,including GRP78,XBP1 were significantly increased at 2h,and increased with times.Western Blot and immunofluorescence results showed that 4-Phenybutyric acid significantly decreased the levels of GRP78 and HIF-1α.Conclusion：Our study demonstrated that paraquat poisoning could up regulate the HIF-1αlevel via endoplasmic reticulum stress.