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抑制外周神经肽Y1及Y2受体改善链脲佐菌素诱导的糖尿病小鼠的压力反射敏感性

牛慧芳, 徐玲, 颜妍, 谢芳, 杨宝峰, 艾静^*

哈尔滨医科大学药理学教研室，省部共建生物医药国家重点实验室,哈尔滨 150081

摘要

神经肽Y (NPY)是一种与心血管自主神经功能障碍和多种心脏疾病都密切相关的交感神经递质。心血管自主神经功能障碍与心血管损伤又有着密切的联系。本文旨在研究参与心血管功能调控并分布于心脏的NPY受体的两个亚型Y1受体(Y1R)和Y2受体(Y2R)对链脲佐菌素(STZ)诱导产生的糖尿病小鼠压力反射敏感性(baroreflex sensitivity, BRS)的影响。将装有NPY Y1R和Y2R特异性拮抗剂(分别为BIBP 3226和BIIE 0246)的ALZET渗透压泵植入到STZ诱导的糖尿病小鼠的皮下4周。然后对小鼠基线收缩压、心率、心功、压力反射敏感性、血浆NPY和脂质水平进行检测。结果显示，STZ可以使血浆NPY水平上升1.64倍(P < 0.05)，血脂升高；STZ的升血脂作用可以被Y1R和Y2R拮抗剂削弱。BIBP 3226可以改善STZ诱导的异常BRS，但对STZ小鼠下降的心功能没有明显作用。BIIE 0246虽然可以改善硝普钠(SNP)介导的STZ小鼠压力反射性心率改变，但对于去氧肾上腺素(PE)介导的压力反射性心率改变没有明显影响。BIIE 0246还可以改善STZ诱导的心动过缓，但却加重了STZ大鼠心功能损伤。以上结果表明，外周NPY Y1及Y2受体对STZ诱导的糖尿病小鼠的BRS损伤中具有不同的作用。

关键词： 神经肽Y; 压力反射敏感性; BIBP 3226; BIIE 0246; 糖尿病

分类号：R587.1

Inhibition of peripheral NPY Y1 and Y2 receptors ameliorates the aberrant baroreceptor reflex sensitivity in streptozotocin induced diabetic rats

NIU Hui-Fang, XU Ling, YAN Yan, XIE Fang, YANG Bao-Feng, AI Jing^*

Department of Pharmacology, Harbin Medical University, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin 150081, China

Abstract

Neuropeptide Y (NPY), a sympathetic neurotransmitter, is highly associated with baroreflex dysfunction and multiple cardiac diseases such as diabetic myocardiopathy. In the present study, we aimed to explore the role of peripheral NPY Y1 receptor (Y1R) and Y2 receptor (Y2R), which are dominantly present in peripheral cardiovascular control, in baroreflex sensitivity (BRS) of streptozotocin (STZ)-induced diabetic rats. Peripheral Y1R and Y2R were antagonized by specific antagonists (BIBP 3226 and BIIE 0246, respectively) from subcutaneously implanted ALZET mini-osmotic pump in STZ-induced diabetic rats for 4 weeks. Then baseline systolic blood pressure, heart rate, cardiac function, BRS, plasma NPY and lipid levels were evaluated. We found that STZ led to increased plasma NPY and lipid level. And the STZ-increased lipid levels were reduced by BIBP 3226 and BIIE 0246. BIBP 3226 ameliorated the aberrant BRS, but had little effect on the impaired cardiac function of the STZ rats. BIIE 0246 alleviated sodium nitroprusside (SNP)-induced but not phenylephrine (PE)-induced aberrant baroreflex control of heart rate in the STZ rats. In addition, BIIE 0246 alleviated the bradycardia, but further impaired cardiac contractility in the STZ rats. These results suggest that peripheral Y1R and Y2R play different roles in STZ-induced impairment of BRS.

Key words: Neuropeptide Y; baroreflex sensitivity; BIBP 3226; BIIE 0246; diabetes mellitus

收稿日期：　　录用日期：

通讯作者：艾静　　E-mail: aijing_86@yahoo.com.cn

引用本文：

牛慧芳, 徐玲, 颜妍, 谢芳, 杨宝峰, 艾静. 抑制外周神经肽Y1及Y2受体改善链脲佐菌素诱导的糖尿病小鼠的压力反射敏感性[J]. 生理学报 2013; 65 (4): 370-380.

NIU Hui-Fang, XU Ling, YAN Yan, XIE Fang, YANG Bao-Feng, AI Jing. Inhibition of peripheral NPY Y1 and Y2 receptors ameliorates the aberrant baroreceptor reflex sensitivity in streptozotocin induced diabetic rats. Acta Physiol Sin 2013; 65 (4): 370-380 (in Chinese with English abstract).