摘要
目的研究罗格列酮对肾缺血再灌注损伤的保护作用及潜在机制。方法将60只大鼠随机分成假手术组、缺血再灌注损伤组、罗格列酮10 mg/kg组、罗格列酮20 mg/kg组、罗格列酮40 mg/kg组和罗格列酮80 mg/kg组,每组各10只。利用血管夹夹闭大鼠双侧肾蒂构建肾缺血再灌注损伤模型。ELISA检测大鼠血清肌酐(Cr)、尿素氮(BUN)、白介素-8(IL-8)、肿瘤坏死因子(TNF-α)和白介素-6(IL-6)表达量;Western blot检测过氧化物酶体增殖物激活受体γ(PPAR-γ)和p-PPAR-γ表达水平;RT-PCR检测肾脏IL-8、TNF-α和IL-6信使核酸序列(mRNA)水平;黄嘌呤氧化酶法检测过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPX)和超氧化物歧化酶(SOD)活性;TBA法检测丙二醛(MDA)的含量;过碘酸雪夫氏(PAS)染色检测肾组织病理形态。结果与假手术组相比,缺血再灌注损伤组肾组织病理损伤和Cr、BUN、IL-8、TNF-α、IL-6、p-PPAR-γ以及MDA表达水平均明显增加,而CAT、GPX和SOD活性明显降低以及PPAR-γ表达差异无统计学意义;与缺血再灌注损伤组相比,罗格列酮预处理可明显减少肾组织病理损伤和Cr、BUN、IL-8、TNF-α、IL-6以及MDA表达水平,但可明显增加CAT、GPX和SOD活性以及p-PPAR-γ表达水平,但对PPAR-γ表达水平无影响。结论罗格列酮预处理对大鼠肾脏缺血再灌注损伤具有保护,其作用机制与激活PPAR-γ抑制氧化应激和炎症相关。
Objective To explore the protective effect and potential mechanism of rosiglitazone(RGZ)on renal ischemia reperfusion injury.Methods Sixty male SD rats were randomly divided in to sham,kidney ischemia reperfusion injury(IRI),RGZ(10 mg/kg),RGZ(20 mg/kg),RGZ(40 mg/kg)and RGZ(80 mg/kg)groups(n=10).The model of IRI was induced by clamping the bilateral renal pedicles.ELISA was used to examine the expression of Cr,BUN,IL-8,TNF-αand IL-6 in the serum.RT-PCR was used to detect the mRNA level of IL-8,TNF-and IL-6 in the kidney.The activation of CAT,GPX and SOD were mesaured by xanthine oxidase.The expression of PPAR-γand p-PPAR-γwere measured by Western blot.The expression of MDA was detected by TBA.The kidney pathological morphology was measured by PAS.Results Compared with the sham group,the kidney pathological injury and the expression of Cr,BUN,IL-8,TNF-α,IL-6,p-PPAR-γand MDA in the IRI group were significantly increased with decreasing the activation of CAT,GPX and SOD.Compared with the IRI group,the kidney pathological injury and the expression of Cr,BUN,IL-8,TNF-α,IL-6,p-PPAR-γand MDA in the RGZ group were significantly decreased with increasing the expression of p-PPAR-γand the activation of CAT,GPX and SOD.There was no difference on the expression of PPAR-γbetween three groups.Conclusions RGZ pretreatment can protect rats againest kidney ischemia-reperfusion injury.The mechanism of which is associated with suppressing inflammation and oxidative stress by activating PPAR-γ.
作者
李昌联
张炯
Li Changlian;Zhang Jiong(Department of Nephrology,Neijiang Second People's Hospital,Neijiang 641003,China;Department of Nephrology,Sichuan Provincial People's Hospital Affiliated to University of science and technology,Chengdu 610072,China)
出处
《国际泌尿系统杂志》
2020年第2期297-301,共5页
International Journal of Urology and Nephrology
基金
国家自然科学基金(81100575)
四川省卫生厅项目(18PJ365)。
关键词
模型
动物
大鼠
再灌注损伤
肾
罗格列酮
Models
Animal
Rats
Reperfusion Injury
Kidney
Rosiglitazone
