褪黑素提高HO-1表达对氯胺酮相关性肾损伤的影响  

Effect of melatonin on ketamine-related renal injury by increasing HO-1

作　　者：曾锦江 卢勇[1] 牛得草[1] 谭伟明[1] 米华[1] ZENG Jinjiang;LU Yong;NIU Decao;TAN Weiming;MI Hua(Department of Urology,the First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi 530021,China)

机构地区：[1]广西医科大学第一附属医院泌尿外科,南宁530021

出　　处：《重庆医学》2018年第32期4107-4111,共5页Chongqing medicine

基　　金：广西自然科学基金资助项目(2017JJA10208);广西高校科学研究项目(2013YB059)

摘　　要：目的探讨氯胺酮致肾脏氧化损伤及褪黑素在其中的治疗作用机制。方法将32只大鼠均分为A、B、C、D 4组,分别给予等量生理盐水、氯胺酮30mg/kg、褪黑素5mg/kg、氯胺酮30mg/kg+褪黑素5mg/kg腹腔注射,连续12周。比色法检测丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽过氧化酶(GSHPx)水平,苏木精-伊红(HE)染色及马松(Masson)染色观察肾组织病理改变,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测肾组织细胞的凋亡情况,Western blot检测血红素氧化酶-1(HO-1)蛋白表达水平。结果与A组比较,B组大鼠血清肌酐、尿素氮及MDA水平升高,SOD及GSH-Px降低,差异均有统计学意义(P<0.05);肾组织可见大量炎症细胞浸润,多处局灶性坏死,甚至出现肾小球萎缩、封闭,间质有条索状纤维,出现明显的细胞凋亡。与B组比较,C组大鼠SOD、GSH-Px及HO-1表达升高(P<0.05),但未见肾损害;D组大鼠MDA水平明显下降,SOD、GSH-Px及HO-1表达明显升高,差异均有统计学意义(P<0.05),且组织炎症浸润、肾小球萎缩、间质纤维化及细胞凋亡等肾损害减少。结论褪黑素可拮抗氯胺酮导致的大鼠肾脏氧化应激损伤,其机制可能与增加HO-1蛋白表达有关。Objective To investigate the efficacy and mechanism of melatonin in treating ketamine-induced kidney damage involved in oxidative stress injury.Methods Thirty-two male rats were divided into groups A,B,C and D,then respectively given normal saline,30 mg/kg ketamine,5 mg/kg melatonin,30 mg/kg ketamine combined with 5 mg/kg melatonin for 12 weeks.Detected the levels of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)by colorimetry,observed the pathological changes of the renal tissue by hematoxylin-eosin(HE)and Masson staining,the apoptotic cells were detected by deoxyribonucleotide terminal transferase labeling(TUNEL),the expression level of heme oxygenase-1(HO-1)was measured by Western blot.Results Compared with group A,the levels of creatinine,urea nitrogen and MDA in group B significantly increased,while SOD and GSH-Px significantly decreased,the difference was statistically significant(P<0.05).There were inflammatory cells infiltration and multiple focal necrosis in renal tissue,furthermore glomerular atrophy and interstitial cord were found in group B,even with a large number of apoptotic cells.Compared with group B,the levels of SOD,GSH-Px and HO-1 increased in group C,the difference was statistically significant(P<0.05),and renal damage was not observed.The level of MDA in group D decreased,the expression of SOD,GSH-Px and HO-1 increased(P<0.05).Inflammatory cells infiltration,glomerular atrophy,renal interstitial fibrosis and apoptosis reduced.Conclusion Melatonin treatment could ameliorate ketamine induce renal oxidative injury via activation of HO-1 expression.

关 键 词：氯胺酮 褪黑素 氧化应激 血红素氧化酶-1 

分 类 号：R692.9[医药卫生—泌尿科学]