褪黑素对慢性肾衰竭大鼠肾脏的保护作用

Protective Effects of Melatonin on Chronic Renal Failure of Rats

目的探讨褪黑素对5/6肾切除慢性肾衰竭大鼠肾脏病理形态和功能的保护作用。方法实验分3组:假手术组、5/6肾切除组、5/6肾切除+褪黑素(5 mg.kg-1.d-1)组,在280 d的观察期内分8个时间段对各组进行肾功能、尿蛋白排泄量、肾质量/体质量测定及残肾组织标本光镜及电镜检查,观察褪黑素对残肾的肾功能和肾脏病理形态的影响。结果5/6肾切除组7 d即出现血清肌酐、尿素氮显著升高,进入氮质血症期,280 d进入肾衰竭期,大部分肾小球纤维化和硬化,肾间质重度纤维化。褪黑素能够部分改善肾功能,显著减少尿蛋白的排泄,延缓进入肾衰竭期;形态学上可以减轻系膜基质的增生、肾小球硬化和肾间质纤维化。结论5/6肾切除是研究局灶节段肾小球硬化和肾间质纤维化逐渐进展所致慢性肾衰竭的理想动物模型。褪黑素对残肾组织的功能和形态有保护作用。

Objective To investigate effects of melatonin on morphological changes and renal function in rat with 5/6 nephrectomy. Methods The SD rats （250 -300 g） were assigned into three groups：sham operated, 5/6 subtotal nephrectomy （STN）, and STN rats given with melatonin（5 mg ·kg^-1·d^-1 ） groups. The levels of renal function and urinary protein, the rate of renal weight and body weight and changes of renal pathology under light and electron microscoPe were observed at eight different time periods of total 280 d. Results The levels of plasma creatinine and blood urea nitrogen were significantly elevated at the 1^st week and developed into renal failure in the 40^th week of STN group. And glomerulis, slight proliferation of mesangial cells and slight dilation of renal tubule were found in STN group. The melatonin partly ameliorated renal function, predominantly reduced urinary protein excretion and retarded the appearance of renal failure. Conclusion The 5/6 nephrectomy on rats is an ideal model of chronic renal failure caused by glomerular sclerosis and renal interstitial fibrosis. Melatonin can protect renal function and morphological change in the remaining kidney.