环氧化酶2在急性肾脏损伤小鼠中的作用机制研究

摘要

目的：研究环氧化酶2（ COX-2）在急性肾损伤中的作用及与内质网应激和自噬的关系。方法24只SPF级小鼠被随机分四组，每组6只。对照组：每天腹腔注射0.9％生理盐水；氯化镉（ CdCl2）组：镉腹腔注射诱导小鼠建立急性肾损伤模型，每天腹腔注射5 mg/kg的CdCl2；塞来昔布（ Celecoxib）组：小鼠腹腔注射COX-2抑药物Celecox-ib；CdCl2+Celecoxib组：小鼠每天早晚各注射一次CdCl2和Celecoxib。收集四组小鼠血液、尿液、肾脏组织样本，检测小鼠血液、尿液中肾脏机制的相关指标，同时检测肾脏组织中内质网应激，自噬相关mRNA、蛋白的表达情况。结果小鼠血液、尿液中肾脏机制的相关指标测定结果显示，药物抑制COX-2能缓解急性肾损伤发病情况。同时，小鼠肾脏mR-NA定量结果和蛋白免疫印迹结果表明，药物抑制COX-2能改善小鼠体内内质网应激和自噬的情况。结论 Celecoxib药物抑制COX-2可以通过调节内质网应激eIF2α-ATF4通路，调节自噬，从而缓解Cd引起的小鼠急性肾损伤的症状。%Objective To study the role of COX-2 in acute kidney injury and the relationship with endoplasmic reticulum stress and au-tophagy. Methods Twenty-four SPF mice were randomly divided into 4 groups,6 in each group. Control group:0. 9% saline was intraperito-neally injected daily. Cadmium chloride( CdCl2 )group:intraperitoneal injection of 5 mg/kg of CdCl2 ,intraperitoneal injection of cadmium intra-peritoneal injection of mice to establish acute kidney injury model. Celecoxib group:mice were injected intraperitoneally with Celecoxib;CoCl2 +Celecoxib group:mice were injected with CdCl2 and Celecoxib once a day. The blood,urine and kidney samples were collected from four groups of mice. The renal mechanism of blood and urine were detected. The expression of endoplasmic reticulum stress and autophagy-related mRNA and protein were also detected. Results The detectting results of blood,urine,kidney in mice indicated that pharmacological inhibition of COX-2 can ease the acute kidney injury. The quantitative results of mRNA and protein related to endoplasmic reticulum stress and autophagy showed that pharmacological inhibition of COX-2 can improve ER stress and autophagy in mice. Conclusion Drugs inhibit COX-2 can adjust the endoplasmic reticulum stress eIF2 alpha ATF4 pathway to regulating autophagy,and alleviating the symptoms of acute kidney injury induced by Cd in mice.