Kisspeptin/kiss1 r系统在营养性肥胖雄性大鼠下丘脑弓状核的表达以及对下丘脑-垂体-睾丸轴的影响  

Expression of the kisspeptin/kiss1 r system in the hypothalamic arcuate nucleus of rats with diet-induced obesity and its influence on the hypothalamic-pituitary-testis axis

作　　者：刘冉冉[1] 张洪芹[1] 

机构地区：[1]滨州医学院烟台校区组织学与胚胎学教研室,山东烟台264003

出　　处：《中华男科学杂志》2014年第9期792-797,共6页National Journal of Andrology

基　　金：山东省自然科学基金(ZR2012HM039)~~

摘　　要：目的:通过构建营养性肥胖雄性大鼠的模型,探讨下丘脑弓状核kisspeptin/kiss1r系统和促性腺激素释放激素(GnRH)的表达和作用,以及对下丘脑-垂体-睾丸轴(HPT)的影响。方法:孕14 d SD大鼠,其后代随机分为正常组和高能饲料组,构建营养性肥胖模型。将肥胖大鼠进一步分为对照组和实验组,实验组侧脑室注入kisspeptin。记录体重参数和内分泌激素的改变;免疫组化和Western印迹检测各组大鼠下丘脑弓状核中瘦素受体(LepR)、kisspeptin、kiss1r和GnRH的蛋白表达。qRT-PCR检测各组大鼠下丘脑弓状核GnRH mRNA的表达。结果:成功构建营养性肥胖大鼠,体重参数和内分泌激素改变明显。相比较正常组,对照组大鼠弓状核LepR、kisspeptin和GnRH表达减少,侧脑室注入kisspeptin后,实验组大鼠弓状核GnRH显著增加,血清LH和T水平显著升高,未见LepR和kiss1r的改变。结论:中枢注入kisspeptin可以显著改善由营养性肥胖引起的GnRH低表达,纠正HPT轴功能失调,进而改善生殖功能。Objective： To explore the expressions and functions of the kisspeptin/kisslr system and GnRH in the hypothalamic arcuate nucleus （HAN） and the influence of the kisspeptin/kisslr system on the hypothalamic-pituitary-testis （HPT） axis in the rat models of diet-induced obesity. Methods ： Ninety newborn SD male rats were randomly assigned to receive normal diet （ n = 30） and high-fat diet （n = 60） for the establishment of obesity models. The model rats were again equally divided into a control group and an experimental group, the latter injected with kisspeptin via the lateral ventricle. Then the body mass index （BMI） and endocrine hor- mone levels of the rats were recorded, the protein expressions of LepR, kisspeptin, kisslr, and GnRH in the HAN determined by im- munohistochemistry and Western blot, and the levels of GnRH mRNA in the HAN measured by qRT-PCR. Results ： Significantly in- creased BMI and hormone levels indicated the successful establishment of diet-induced obesity models. Compared with the normal rats, the protein expressions of LepR, kisspeptin, and GnRH in the HAN were markedly decreased in the controls, and that of GnRH and the levels of LH and T significantly increased, but the expressions of LepR and kisslr showed no remarkable changes in the experimen- tal rats. Conclusion ： Lateral ventricular injection of kisspeptin can upregnlate obesity-induced low expression of GnRH, correct the dysfunction of the HPT axis, and thus improve reproductive function in rats.

关 键 词：kisspeptin/kiss1r系统 促性腺激素释放激素 瘦素受体 肥胖 下丘脑-垂体-睾丸轴 大鼠 

分 类 号：R589.2[医药卫生—内分泌]