褪黑素对肾血管性高血压大鼠肾脏损伤的影响及机制  

Protective effects of melatonin against kidney injury of renovascular hypertensive rats and related mechanisms

作　　者：郭文娟[1] 王利华[1] 李荣山[1] 李璐[1] 乔晞[1] 邵珊[1] 

机构地区：[1]山西医科大学第二医院肾内科,山西省肾脏病研究所,太原030001

出　　处：《中华高血压杂志》2011年第9期831-835,共5页Chinese Journal of Hypertension

摘　　要：目的观察褪黑素(MT)抗氧化应激作用对两肾一夹(2K1C)高血压大鼠肾损害的保护作用并探讨其机制。方法用分离结扎左肾动脉的方法制备2K1C肾血管性高血压大鼠模型,造模成功后,随机分为2组:高血压组(2K1C组)、褪黑素组(MT组),每组8只。假手术组大鼠8只作为对照。观察8周,监测血压,HE染色观察肾脏组织病理损伤,比色法检测肾组织超氧化物岐化酶(SOD)和脂质过氧化物丙二醛含量。免疫组织化学染色及RT-PCR检测诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)表达。结果 HE染色结果显示,造膜成功后8周,高血压组肾小管及间质呈现明显的病理损伤,表现为肾小管上皮细胞空泡及颗粒变性,有炎性细胞浸润、肾小管水肿扩张,甚至萎缩,褪黑素组肾组织病理损伤则明显轻于高血压组;术后第4周开始,高血压组大鼠血压即明显高于假手术组,而褪黑素能抑制大鼠血压的升高。与假手术组相比,高血压组大鼠肾组织丙二醛含量升高[(21.23±4.26)比(12.08±2.33)nmol/mg,P<0.01],SOD活性降低[(329.76±23.87)比(449.95±44.67)U/mg,P<0.01];褪黑素组SOD活性较高血压组升高[(379.53±34.82)比(329.76±23.87)U/mg,P<0.01],丙二醛含量较高血压组降低[(16.66±4.71)比(21.23±4.26)nmol/mg](P<0.01)。免疫组织化学染色及RT-PCR检测结果显示,高血压组肾组织eNOS表达较假手术组降低,iNOS表达升高;褪黑素组肾组织eNOS含量较高血压组升高,iNOS含量降低(均P<0.01)。结论褪黑素能抑制iNOS表达,增加eNOS表达,减轻高血压大鼠肾小管间质损伤。Objective To investigate the protective effects of melatonin（MT） against kidney injury in reno-hypertensive rats（two kidneys one clip model,2K1C） and relevant mechanisms.Methods Renovascular hypertension was induced in male Wistar rats by the two-kidney one-clip（2K1C） method.The model rats were randomized into untreated 2K1C group and MT-treated 2K1C group（n=8,respectively）.Another 8 rats were selected as controls in the sham operation group.After 8 weeks of follow-up,we monitored their blood pressure.Kidney histological changes were examined by hematoxylin and eosin（HE） staining.Renal superoxide dismutase（SOD） activity and malondialdehyde（MDA） contents were detected by colorimetric method.The expressions of inducible nitric oxide synthase（iNOS） and endothelial nitric oxide synthase（eNOS） in renal tissue were detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction（RT-PCR）,respectively.Results ① Four weeks after surgery,increased aortic pressure was present in 2K1C rats as compared with those in the sham operation group,and treatment with MT attenuated the increase（all P〈0.05）.② Rats subjected to 2K1C displayed markedly worsened renal histological changes compared with sham controls.In contrast,MT significantly attenuated morphological damage（all P〈0.01）.③ 2K1C hypertension resulted in increased MDA content and decreased SOD activity.MT pretreatment significantly reversed the above changes.④ Renal iNOS expression was up-regulated in 2K1C rats,while eNOS expression significantly down-regulated.MT inhibited the upregulation of iNOS and the downregulation of eNOS in the clipped kidneys of 2K1C rats.Conclusion Melatonin could exert protection [BHDWG6,WK49ZQ0W]against hypertension-induced renal tubulointerstitial injury,at least partly,by inhibiting iNOS expression and increasing eNOS expression.

关 键 词：高血压肾损害 氧化应激 褪黑素 诱导型一氧化氮合酶 内皮型一氧化氮合酶 

分 类 号：R544.1[医药卫生—心血管疾病]