氧化应激和Cyt-C/Caspase-9/Caspase-3信号途径在镉致大鼠肾脏损伤中的作用  

Mechanism of oxidative stress and Cyt-C/Caspase-9/Caspase-3 signaling pathway in rat kidney induced by cadmium

作　　者：黄茹雪 叶颖 王珂 丁璐璐 于文静 燕炳兆 汪纪仓[1] 刘宗平[2] HUANG Ru-xue;YE Ying;WANG Ke;DING Lu-lu;YU Wen-jing;YAN Bing-zhao;WANG Ji-cang;LIU Zong-ping(College of Animal Science and Technology,Henan University of Science and Technology,Luoyang 471003,China;College of Veterinary Medicine,Yangzhou University,Yangzhou 225009,China)

机构地区：[1]河南科技大学动物科技学院,河南洛阳471003 [2]扬州大学兽医学院,江苏扬州225009

出　　处：《中国兽医科学》2022年第5期661-670,共10页Chinese Veterinary Science

基　　金：国家自然科学基金项目(31972753);河南省科技攻关项目(222102110340)。

摘　　要：为了探究氧化损伤和Cyt-C/Caspase-9/Caspase-3信号途径在镉导致大鼠肾脏损伤中的作用机制,18只雄性SD大鼠,分为3组并每天按以下处理:对照组腹腔注射生理盐水,低、高剂量镉组分别腹腔注射1 mg/kg、2 mg/kg CdCl_(2)溶液,注射剂量均为10 mL/kg。4周后,麻醉大鼠并将其处死,摘除肾脏称重并计算脏器系数,测定肾功能相关指标含量的变化,制作肾脏病理切片并用光镜观察,用TUNEL法观察肾脏细胞凋亡情况,荧光定量PCR和Western-blot法检测凋亡相关基因mRNA和蛋白的表达量。结果显示,与对照组相比,低、高剂量镉组肾脏系数升高(P>0.05)或极显著升高(P<0.01);大鼠血清中尿酸(UA)、肌酐(CRE)、尿素氮(BUN)含量显著或极显著升高(P<0.05或P<0.01);肾脏组织中谷胱甘肽(GSH)、丙二醛(MDA)含量上升或极显著上升(P<0.05或P<0.01);病理切片显示镉可引起小管腔狭窄、肾间质充血等病理损伤;TUNEL凋亡细胞的数目显著增加(P<0.05或P<0.01);肾脏组织中Cyt-C、Caspase-9、Caspase-3 mRNA的表达量及蛋白表达水平增加或极显著增加(P<0.05或P<0.01)。上述结果表明,氧化损伤和细胞凋亡在镉致大鼠肾脏损伤中发挥着重要作用。To explore the mechanism of oxidative damage and Cyt-C/Caspase-9/Caspase-3 signaling pathway in cadmium-induced renal injury in rats.eighteen male SD rats were divided into 3 groups and treated as follows every day.The control group was intraperitoneally injected with normal saline.Low and high dose groups Cd were intraperitoneally injected with 1 mg/kg.b.w and 2 mg/kg.b.w CdCl_(2) solution(10 mL/kg).After 4 weeks,the rats were anaesthetized and sacrificed.The rat’s body weight and relative kidney weight were measured.The changes of renal function related indexes were determined.The pathological section of the kidney was observed.The apoptosis of renal cells was detected by TUNEL assay.The expression of apoptotic gene expression and apoptosis-related proteins were detected by fluorescence quantitative PCR mRNA expression and Western blot.The results showed that compared with the control group,the renal coefficient of the low and high Cd-treated group increased or significantly increased(P>0.05 or P<0.01).The contents of Uric acid(UA),Creatinine(CRE)and Blood Urea Nitrogen(BUN)in serum increased or significantly increased(P<0.05 or P<0.01),the contents of glutathione(GSH)and malondialdehyde(MDA)in the kidney tissues increased or significantly increased(P<0.05 or P<0.01).Pathological section showed that cadmium can cause pathological damages such as narrow lumen and renal interstitial congestion.The number of TUNEL apoptotic cells were significantly increased(P<0.05 or P<0.01),the expression of Cyt-C,Caspase-9,Caspase-3 mRNA and protein expression in kidney tissues increased or extremely significantly(P<0.05 or P<0.01).This experiment results showed that oxidative damage and apoptosis play an important role in cadmium-induced kidney damage in rats.

关 键 词：镉 肾脏 凋亡 氧化应激 Cyt-C/Caspase-9/Caspase-3 

分 类 号：S856.9[农业科学—临床兽医学]