室旁核黑皮质素受体4调控瘦素对2型糖尿病大鼠交感神经活性和压力感受性反射功能影响的研究

Regulation of melanocortin receptor-4 on leptin affecting the sympathetic activity and baroreflex function of type 2 diabetic rats

目的 研究室旁核(PVN)黑皮质素受体4(MC4R)调控瘦素(LPN)对T2DM大鼠交感神经活性(SNA)和压力感受性反射功能的影响.方法 选取SD大鼠予高糖高脂饲料联合STZ(30 mg/kg)腹腔注射制备糖尿病模型,最终造模成功T2DM大鼠20只.依据双侧PVN显微注射人工脑脊液(aCSF)和MC4R抑制剂SHU9119,随机分为PVN-aCSF组和PVN-SHU9119组,每组各10只.两组于麻醉下行1 h侧脑室LPN输注,并测定大鼠的SNA、平均动脉压(MAP)、心率(HR),绘制压力感受性反射曲线.继续输注LPN的同时在PVN注射aCSF或SHU9119,并绘制压力感受性反射曲线.结果 与各自Con压力感受性反射曲线相比,PVN-aCSF、PVN-SHU9119组输注1 h LPN后的SNA、MAP、HR升高(P<0.05),PVN注射SHU9119后的SNA、MAP及HR低于PVN-aCSF组(P<0.05);PVN-SHU9119组的交感神经压力反射功能参数 Max、Min 低于 PVN-aCSF 组(P<0.05).结论T2DM大鼠MC4R在PVN参与LPN增加SNA和调节压力感受性反射功能.

Objective To study the effect of melanocortin 4 receptor(MC4R)in paraventricular nucleus(PVN)regulating the influence of leptin(LPN)on sympathetic nerve activity(SNA)and baroreflex function in type 2 diabetic rats.(30 mg/kg)intraperitoneal injection to establish DM model.20 T2DM rats were randomly microinjected with artificial cerebrospinal fluid(aCSF)in PVN(PVN-aCSF group,n=10)or MC4 R inhibitor-SHU9119(PVN-SHU9119 group,n=10).The control(Con)baroreflex curves were firstly plotted in a steady state.After leptin infusion for 1 hour,SNA,mean arterial pressure(MAP)and heart rate(HR)were measured and baroreflex curves were plotted.Then,the curve was again drawn while simultaneously microinjecting Results Compared with the Con state,the values of SNA,MAP and HR after 1 h LPN infusion were significantly increased in DM rats(P<0.05).The levels of SNA,MAP and HR after SHU9119 microinjection were lower than those in PVN-aCSF group(P<0.05),also the Max and Min function parameters of sympathetic baroreflex(P<0.05).Conclusion MC4R may be involved in the process of leptin increasing SNA and regulating baroreflex function via PVN in DM rats.