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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NPYY1R和Y2R特异性拮抗剂(分别为BIBP3226和BIIE0246)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。BIBP3226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。BIIE0246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。BIIE0246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NPYY1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。
Neuropeptide Y (NPY) is a sympathetic neurotransmitter that is closely associated with cardiovascular autonomic dysfunction and various heart diseases. Cardiovascular autonomic dysfunction and cardiovascular damage are closely linked. This study aimed to investigate the effects of two subtypes of Y1R (Y1R) and Y2R (Y2R) NPY receptors involved in cardiovascular regulation and distribution in the heart on diabetic mice induced by streptozotocin (STZ) Effects of baroreflex sensitivity (BRS). ALZET osmotic pumps containing NPYY1R and Y2R specific antagonists (BIBP3226 and BIIE0246, respectively) were implanted subcutaneously in STZ-induced diabetic mice for 4 weeks. Then baseline systolic blood pressure, heart rate, heart function, baroreflex sensitivity, plasma NPY and lipid levels were measured. The results showed that STZ increased plasma NPY level 1.64-fold (P <0.05) and increased blood lipids; STZ hyperlipidemia was attenuated by Y1R and Y2R antagonists. BIBP3226 can improve STZ-induced abnormal BRS, but has no significant effect on decreased cardiac function in STZ mice. BIIE0246, although able to improve sodium nitroprusside (SNP) -mediated STZ-induced baroreflex heart rate changes, had no significant effect on phenylephrine (PE) -mediated stress reflex heart rate changes. BIIE0246 also improves STZ-induced bradycardia but aggravates cardiac function in STZ rats. The above results indicate that peripheral NPYY1 and Y2 receptors have different effects on BRS injury in STZ-induced diabetic mice.