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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 investigate the expression and effect of kisspeptin / kiss1r system and gonadotropin-releasing hormone (GnRH) in the hypothalamic arcuate nucleus and the effects on hypothalamic-pituitary-testicular axis (HPT) influences. Methods: The 14-day pregnant SD rats were randomly divided into normal group and high-energy diet group to construct a model of nutritional obesity. The obese rats were further divided into the control group and the experimental group. The experimental group injected kisspeptin into the lateral ventricle. The changes of body weight parameters and endocrine hormones were recorded. The protein expressions of Leptin, kisspeptin, kiss1r and GnRH in hypothalamic arcuate nucleus were detected by immunohistochemistry and Western blotting. qRT-PCR was used to detect the expression of GnRH mRNA in hypothalamic arcuate nucleus in each group. Results: The successful establishment of nutritional obese rats, body weight parameters and endocrine hormones changed significantly. Compared with the normal group, the expression of LepR, kisspeptin and GnRH in the arcuate nucleus of the control group decreased. After injection of kisspeptin into the lateral ventricle, the GnRH of the arcuate nucleus of the experimental group increased significantly and the levels of serum LH and T were significantly increased. Kiss1r change. Conclusions: Kisspeptin injected into the central can significantly improve the low expression of GnRH caused by nutritional obesity, correct the dysfunction of HPT axis and improve the reproductive function.