Klotho对CsA慢性肾毒性大鼠肾脏内质网应激相关凋亡的影响  

Klotho Ameliorates Cyclosporine-induced Chronic Nephrotoxicity Via Inhibition of Endoplasmic Reticulum Stress

作　　者：李莎莎[1] 邓志勇[2] 何敖林[1] 叶建明[3] 刘其锋[3] 

机构地区：[1]昆山市第一人民医院临床实验研究中心,中国江苏昆山215300 [2]昆山市第一人民医院病理科,中国江苏昆山215300 [3]昆山市第一人民医院肾脏内科,中国江苏昆山215300

出　　处：《生命科学研究》2015年第5期422-425,共4页Life Science Research

基　　金：苏州市"科教兴卫"青年科技项目(KJXW2014049);江苏大学临床科技发展基金项目(JLY20140061)

摘　　要：24只雄性SD(Sprague dawley)大鼠在低盐饮食的基础上,随机分为3组:对照组、模型组、治疗组。模型组给予环孢素A(Cyclosporin A,Cs A)30 mg/kg/d腹腔注射共28 d建立慢性肾毒性大鼠模型;治疗组在给予等量Cs A的基础上腹腔注射给予重组可溶性Klotho蛋白(0.02 mg/kg/d腹腔注射,隔日一次)。28 d后处死大鼠,收集肾组织标本;行Masson染色观察肾脏病理损害;TUNEL(Td T-mediated d UTP nick end labeling)染色观察细胞凋亡情况;Western-blot检测肾组织内质网应激标志物兔抗葡萄糖调节蛋白78(glucose regulated protein78,GRP78)及CCAAT/增强子结合蛋白同源蛋白(pro-apoptotic protein CCAAT/enhancer binding protein homologous protein,CHOP)的表达情况。分析发现,模型组大鼠肾脏病理损害明显加重,肾小管上皮细胞大量凋亡,GRP78及CHOP表达显著上调,而Klotho治疗组大鼠肾脏病理损害明显减轻,细胞凋亡减少,GRP78及CHOP的表达明显降低。表明Klotho蛋白可通过抑制内质网应激诱导的凋亡缓解Cs A慢性肾毒性的发生。24 male Sprague dawley （SD） rats on a low-sodium diet were randomly divided into control group （olive oil, 1 mL/kg/d, i.p.）, model group （CsA, 30 mg/kg/d, i.p.） and Klotho group （CsA, 30 mg/kg/d and Klotho 0.02 mg/kg, every other day, i.p.）. Renal pathological changes were evaluated by Masson＇s trichrome staining. Apoptosis was assessed by TUNEL assay and endoplasmic reticulum stress was estimated by detection of GRPT8 and CHOP. Administration of CsA for 28 d caused renal lesions and increased the apoptosis, while Klotho treatment ameliorated these pathological changes. CsA treatment upregulated indicators of ER stress including GRP78 and CHOP, while Klotho prevented the increase in these indicators of ER stress. Collectively, Klotho therapy attenuates apoptosis via inhibiting ER stress in a rat model of chronic CsA-induced nephropathy.

关 键 词：KLOTHO 环孢素A慢性肾毒性 内质网应激 细胞凋亡 

分 类 号：R58[医药卫生—内分泌]