黑皮质素受体-4在正常大鼠瘦素诱发交感神经活性和压力感受性反射功能变化中的作用

Effects of melanocortin 4 receptor on leptin-induced sympathetic nerve activity and baroreflex function in normal rats

目的探讨黑皮质素受体-4(MC4R)在瘦素(LPN)诱发的正常大鼠交感神经活性(SNA)和压力感受性反射功能变化中的作用。方法将正常SD大鼠20只随机分为室旁核(PVN)-人工脑脊液(aCSF)组和PVNSHU9119组,分别在双侧PVN显微注射aCSF和MC4R抑制剂SHU9119,每组10只。两组大鼠于侧脑室注射LPN0 h、LPN 1 h后绘制压力感受性反射曲线;继续注射LPN的同时分别在PVN显微注射aCSF和MC4R抑制剂SHU9119,并绘制压力感受性反射曲线,同时记录注射LPN 0 h、LPN 1 h及PVN注射aCSF或SHU9119后的基础血压(MAP)、HR、SNA值。结果 PVN-aCSF组和PVN-SHU9119组中,与本组注射LPN 0 h相比,注射LPN 1 h后和PVN注射后的SNA、HR均升高(P均<0.05),但PVN注射SHU9119后的SNA、MAP及HR值均低于同时期PVNaCSF组的对应值(P均<0.05)。两组交感神经压力感受性反射功能参数比较,与各自注射LPN 0 h相比,注射LPN 1 h后和PVN注射后的Max、Min均升高(P均<0.05),PVN-SHU9119组的Max低于同时间PVN-aCSF组的对应值(P<0.05)。两组心率压力感受性反射功能参数比较,与本组注射LPN 0 h相比,注射LPN 1 h后和PVN注射后的Max、BP50均升高(P<0.05),但PVN注射SHU9119后的Max低于注射LPN 1 h后的Max(P<0.05)。PVNSHU9119组的Max、Min、BP50值低于同时间PVN-aCSF组(P<0.05)。结论 PVN的MC4R部分参与LPN诱发的正常大鼠交感神经活性和压力感受性反射功能增强。

Objective To study the effects of melanocortin4receptor in regulating the influence of leptin on sympathetic nerve activity and baroreflex function in normal rats.Methods Twenty normal rats were randomly divided into the PVN-aCSF and the PVN-SHU9119group,which were microinjected with artificial cerebrospinal fluid(aCSF)in paraventricular nucleus(PVN),and MC4R inhibitor-SHU9119,respectively.After lateral ventricle leptin infusion for0and1h,we drew baroreflex curve.While being infused leptin continually,both groups were microinjected with aCSF and MC4R inhibitor-SHU9119,respectively,and then we drew the PVN-aCSF/PVN-SHU9119baroreflex curve.At the same time,we recorded the basic values of BP,HR,and SNA in0h LPN,1h LPN,PVN-aCSF and PVN-SHU9119.Results In the PVN-aCSF and the PVN-SHU9119group,the SNA value after1h LPN infusion and PVN microinjection increased as compared with that at0h LPN(P<0.05).The levels of SNA,MAP,and HR after PVN microinjection of SHU9119were lower than the corresponding levels of the PVN-aCSF group at the same time(all P<0.05).The comparison of sympathetic baroreflex function parameters between the two groups showed that the degrees of Max and Min after1h LPN infusion and PVN microinjection were higher than each degree in0h LPN(P<0.05).The level of Max after PVN microinjection of SHU9119was lower than the corresponding level of the PVN-aCSF group at the same time(P<0.05).The results of HR baroreflex function parameters between the two groups demonstrated that,compared with their respective0h LPN,the Max and BP50after1hLPN infusion and PVN microinjection increased(both P<0.05).The level of Max after PVN microinjection of SHU9119was significantly lower than that at1h LPN infusion(P<0.05).The levels of Max,Min,and BP50after PVN microinjection of SHU9119were lower than the corresponding levels of the PVN-aCSF group at the same time(all P<0.05).Conclusion MC4R enhances leptin-induced sympathetic nerve activity and baroreflex function in normal rats.