STZ-糖尿病大鼠下丘脑和胰腺神经肽Y的mRNA及蛋白表达研究(英文)

Increased expression of neuropeptide Y and its mRNA in STZ-diabetic rats

目的 研究糖尿病大鼠下丘脑和胰腺神经肽Y的mRNA及蛋白表达情况 ,以探讨NPY和糖尿病的关系。方法 建立链脲佐菌素 (STZ)诱导的糖尿病大鼠模型 ,设立糖尿病、糖尿病胰岛素治疗及对照组 ,饲养 2 4周后处死动物。用原位杂交和免疫组化检测下丘脑和胰腺NPY的mRNA及蛋白表达情况。结果 1.糖尿病大鼠下丘脑NPY的mRNA及蛋白表达均增加 ,NPY的mRNA表达主要在弓状核 ,说明弓状核是NPY产生的主要部位。 2 .给予胰岛素治疗后 ,STZ糖尿病大鼠下丘脑的NPY的mRNA及蛋白表达均较糖尿病组明显下降 ,说明胰岛素缺乏是STZ糖尿病大鼠下丘脑NPY增多的重要原因之一。 3.下丘脑NPY增高的糖尿病大鼠具有多饮、多食 ;胰岛素治疗后其NPY下降 ,糖尿病大鼠的多饮、多食明显缓解 ,证实NPY参与STZ糖尿病大鼠的某些病理生理过程。 4 .首次揭示在STZ糖尿病大鼠胰岛中NPY的mRNA及蛋白表达增加。胰岛素NPY阳性细胞的分布也发生改变 ,由主要分布在周边变为整个胰岛散在分布 ,给予胰岛素治疗后 ,胰岛中的NPY和mRNA及蛋白表达未见明显改变。结论 糖尿病下丘脑NPY的增多 ,主要参与糖尿病的多饮、多食等病理生理过程。虽然糖尿病胰岛的NPY增多原因及其作用还不完全清楚 ,但为今后进一步的研究提供了重要线索。

OBJECTIVE: To study the relationship between neuropeptide Y (NPY) and diabetes by examining the content and distribution of NPY and its mRNA expression in the hypothalamus and pancreas of STZ-diabetic rats. METHODS: Thirty Wistar rats were randomly divided into 3 groups (diabetic group, diabetic insulin treatment group, and control group). After feeding for 24 weeks, the rats were sacrificed. The expression of NPY in the hypothalamus and pancreas was detected with immunohistochemistry and in situ hybridization. RESULTS: (1) The hypothalamic content of NPY and its mRNA were significantly increased in STZ-diabetic rats in comparison with normal controls. Increased expression of NPY mRNA was found only in the arcuate nucleus and not in the paraventricular nucleus in diabetic rats, suggesting that NPY was produced in the arcuate nucleus. (2) The hypothalamic content of NPY and its mRNA in STZ-diabetic rats were visibly reduced after insulin treatment compared with that in untreated diabetic rats. This supports the hypothesis that insulin deficiency in the brain may be responsible for increased hypothalamic NPY gene expression in diabetic rats. (3) The increase of hypothalamic NPY in STZ diabetic rats associated with hyperphagia and polydipsia could be reversed by insulin replacement, suggesting that increased hypothalamic NPY contributes to the pathophysiological progress of the diabetic state. (4) The present study demonstrated for the first time that the content of NPY and its mRNA in the pancreas was increased in STZ-diabetic rats, and that the distribution of NPY-positive cell in islets was changed from the periphery to the whole islet. The content and distribution of NPY and its mRNA in islets were not changed by insulin treatment. CONCLUSION: Increased NPY in the hypothalamus results in hypophagia and polydipsia, while the implication of increased NPY in the pancreas of diabetic rats is not clear.