摘要
目的分析由顺铂诱导小鼠急性肾损伤(AKI)肾组织中炎症与Klotho蛋白的表达变化及相关性,探讨Klotho在顺铂致AKI中的作用及可能机制。方法18只雄性C57BL/6小鼠随机分为0 d组、1 d组、3 d组,每组6只。给予单次腹腔注射顺铂25 mg/kg,分别于0、1、3 d处死小鼠,留取血清、肾脏组织。生化分析仪检测肌酐(Scr)和血尿素氮(BUN)含量,HE染色观察肾脏组织病理变化,Western blot法检测中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肿瘤坏死因子α(TNF-α)、含pyrin结构域NOD样受体家族3(NLRP3)、Klotho、信号转导子与转录激活子3(STAT3)、磷酸化STAT3(p-STAT3)、核因子κB(NF-κB)、磷酸化NF-κB(p-NF-κB)蛋白表;采用Spearman秩相关检验进行相关性分析。结果与0 d组相比,1 d和3 d组血清Scr、BUN含量均显著性增高;1 d和3 d组小鼠肾组织间质出现炎症细胞浸润,肾小管上皮细胞脱落、水肿、细胞碎片大量堆积;3 d组肾组织NGAL、TNF-α、NLRP3、p-STAT3、STAT3、p-NF-κB、NF-κB蛋白含量明显增高,其中TNF-α、p-STAT3、STAT3表达量增高呈时间依赖性;1 d和3 d组Klotho表达量降低呈时间依赖性;NGAL、TNF-α、NLRP3、p-STAT3、p-NF-κB与Klotho的表达均呈显著负相关。结论Klotho激活STAT3/NF-κB通路参与调控顺铂诱导小鼠AKI的发生发展。
Objective To analyze the changes and correlation between inflammation and Klotho expression in kidney tissue of mice with acute kidney injury(AKI) induced by cisplatin, and to explore the role and possible mechanism of Klotho in AKI induced by cisplatin. Methods Eighteen male C57BL/6 mice were randomly divided into 0-day group, 1-day group and 3-day group with 6 mice in each group. The mice were killed at 0, 1 and 3 days after a single intraperitoneal injection of 25 mg/kg of cisplatin, and the serum and kidney tissues were collected. The content of serum creatinine(Scr) and blood urea nitrogen(BUN) were measured by biochemical analyzer, and the pathological changes of kidney tissues were observed by HE staining. Neutrophil gelatinase-associated lipocalin(NGAL), tumor necrosis factor α(TNF-α), NLR family pyrin domain containing 3(NLRP3), Klotho, signal transducer and activator of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), nuclear factor-kappa B(NF-κB), phosphorylated NF-kappa B(p-NF-κB) were detected by Western blot analysis. Spearman rank correlation test was used to analyze the correlations. Results The content of serum Scr and BUN in 1-day and 3-day groups were significantly higher than those in 0-day group, and inflammatory cell infiltration, renal tubular epithelial cell exfoliation, edema and accumulation of cell fragments were seen in 1-day and 3-day groups. In the 3-day group, the content of NGAL, TNF-α, NLRP3, p-STAT3, STAT3, p-NF-κB and NF-κB proteins in renal tissues significantly increased, and the expression of TNF-α, p-STAT3 and STAT3 increased in a time-dependent manner. The expression of Klotho decreased in a time-dependent manner in the 1-day and 3-day groups, and the expression of NGAL, TNF-α, NLRP3, p-STAT3, and p-NF-κB were significantly negatively correlated with the expression of Klotho. Conclusion The activation of STAT3/NF-κB pathway by Klotho is involved in the regulation of the occurrence and development of AKI induced by cisplatin in mice.
作者
伍聪聪
刘丽荣
徐卫卫
简久莹
张妮
王笑笑
郭兵
WU Congcong;LIU Lirong;XU Weiwei;JIAN Jiuying;ZHANG Ni;WANG Xiaoxiao;GUO Bing(Department of Clinical Hematology,School of Clinical Laboratory Science,Guizhou Medical University,Guiyang 550004;Department of Blood Transfusion,Guiyang Municipal First People's Hospital,Guiyang 550002;Laboratory of Pathogenesis Research,Department of Pathophysiology,School of Basic Medicine,Guizhou Medical University,Guiyang 550025,China)
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2019年第8期702-706,共5页
Chinese Journal of Cellular and Molecular Immunology
基金
国家自然科学基金(81860134)
贵州省高层次留学人才创新创业择优资助项目(留学人才择优资助合同(2018)01号)
