Klotho对CsA慢性肾毒性大鼠肾脏内质网应激相关凋亡的影响

被引:14
作者
李莎莎 [1 ]
邓志勇 [2 ]
何敖林 [1 ]
叶建明 [3 ]
刘其锋 [3 ]
机构
[1] 昆山市第一人民医院临床实验研究中心
[2] 昆山市第一人民医院病理科
[3] 昆山市第一人民医院肾脏内科
关键词
Klotho; 环孢素A慢性肾毒性; 内质网应激; 细胞凋亡;
D O I
10.16605/j.cnki.1007-7847.2015.05.012
中图分类号
R285.5 [中药实验药理];
学科分类号
100806 [中药药理学];
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。
引用
收藏
页码:422 / 425
页数:4
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