过氧化物酶体增殖物激活受体γ在急性缺氧肾损伤大鼠肾脏组织中的表达及其意义

Expression and significance of peroxisome proliferator-activated receptor γ in renal tissue of rats with acute hypoxia renal injury

目的:探讨过氧化物酶体增殖物激活受体γ(PPARγ)在急性缺氧肾损伤大鼠肾脏组织中的表达及其意义。方法:将24只雄性SD大鼠随机分为正常对照组、PPARγ激动剂组、PPARγ抑制剂组和缺氧损伤组,每组6只。通过腹腔内注射给予PPARγ激动剂组罗格列酮(10 mg/kg·d^(-1)),PPARγ抑制剂组GW9662(1 mg/kg·d^(-1)),每天1次,共3 d。正常对照组不做任何处理,其余3组放入模拟高度7500 m低压低氧舱内,7 h后处死大鼠,取左肾组织进行病理学检查,分别采用实时荧光定量PCR(RTqPCR)和Western blotting检测大鼠肾组织PPARγ、超氧化物歧化酶(SOD)、白介素-1β(IL-1β)、内皮素(ET-1)的mRNA及其蛋白表达。结果:与正常对照组相比,PPARγ激动剂组、PPARγ抑制剂组和缺氧损伤组的大鼠均出现肾小管上皮细胞(RTEC)肿胀、脱落,线粒体肿胀;与缺氧损伤组相比,PPARγ激动剂组大鼠RTEC肿胀减轻,PPARγ抑制剂组大鼠RTEC线粒体嵴减少。与正常对照组相比,缺氧损伤组大鼠肾组织PPARγ和SOD的mRNA及其蛋白表达量均降低(均P<0.05);IL-1β和ET-1的mRNA及其蛋白表达量均升高(均P<0.05)。与缺氧损伤组相比,PPARγ激动剂组大鼠肾组织PPARγ和SOD的mRNA及其蛋白表达量均升高(均P<0.05),IL-1β和ET-1的mRNA及其蛋白表达量均降低(均P<0.05);PPARγ抑制剂组大鼠肾组织PPARγ和SOD的mRNA及其蛋白表达量均降低(均P<0.05),IL-1β和ET-1的mRNA及其蛋白表达量均升高(均P<0.05)。结论:在急性缺氧肾损伤大鼠中,肾脏组织PPARγ的表达降低并参与了肾损伤,PPARγ激动剂罗格列酮可减轻大鼠缺氧性肾损伤,而PPARγ抑制剂GW9662则加重大鼠缺氧性肾损伤。

Objective:To investigate the expression and significance of peroxisome proliferator-activated receptorγ(PPARγ)in renal tissue of rats with acute hypoxia renal injury.Methods:A total of 24 male SD rats were randomly divided into normal control group,PPARγagonist group,PPARγinhibitor groupand hypoxia injury group,with 6 cases in each group.Rosiglitazone(10 mg/kg·d^(-1))in PPARγagonist group and GW9662(1 mg/kg d^(-1))in PPARγ inhibitor group were injected intraperitoneally once a day for 3 days.The rats in the normal control group did not receive any treatments.The rats in the other three groups were put into a hypobaric hypoxia chamber with a simulated height of 7500m.The rats were euthanized 7 hours later,and the left kidney tissue was taken for pathological examination.The mRNA and protein expressions of PPARγ,superoxide dismutase(SOD),interleukin-1β(IL-1β)and endothelin(ET-1)in renal tissue were detected by real-time reverse transcription-quantitative PCR(RT-qPCR)and Western blotting,respectively.Results:Compared with the normal control group,PPARγ agonist group,PPARγ inhibitor group and hypoxia injury group all showed renal tubular epithelial cell(RTEC)swelling,exfoliation and mitochondrial swelling;compared with hypoxia injury group,RTEC swelling was alleviated in PPARγ agonist group and RTEC mitochondrial crest decreased in PPARγ inhibitor group.Compared with the normal control group,the mRNA and protein expression of PPARγ and SOD in renal tissue of hypoxic injury group decreased(all P<0.05);the mRNA and protein expression of IL-1β and ET-1 increased(all P<0.05).Compared with hypoxic injury group,the mRNA and protein expression of PPARγand SOD in renal tissue of PPARγ agonist group increased(all P<0.05),while the mRNA and protein expression of IL-1β and ET-1 decreased(all P<0.05);In PPARγ inhibitor group,the mRNA and protein expression of PPARγ and SOD decreased(all P<0.05),while the mRNA and protein expression of IL-1β and ET-1 increased(all P<0.05).Conclusion:In rats with acute hypoxic renal injury,the expression of PPARγ in renal tissue decreases and participates in renal injury.PPARγagonist rosiglitazone can alleviate hypoxic renal injury,while PPARγinhibitor GW9662 can aggravate hypoxic renal injury.