大川芎方抑制血管紧张素Ⅱ诱导高血压模型的异常交感神经活动和脑内NADPH氧化酶表达

Inhibitory Effect of Dachuanxiong Decoction on Abnormal Sympathetic Nerve Activities and Brain NADPH Oxidase Expression in Hypertensive Rats Induced by AngiotensinⅡ

目的观察大川芎方对血管紧张素Ⅱ(AngⅡ)诱导高血压模型的异常交感神经活性、压力反射敏感性和室旁核AngⅡ-1型受体(AT1R)-烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶信号通路的影响。方法经植入ALZET微渗透泵的雄性SD大鼠,慢性灌流AngⅡ结合高盐饮食建立高血压模型,并随机分为假性操作对照组(CON)、模型组(M)、大川芎方高剂量组(DH)、大川芎方低剂量组(DL)和氯沙坦组(L),每组9只。无创血压系统测量清醒大鼠尾动脉血压,电生理记录肾交感神经活动,Smyth方法评估压力反射敏感性,ELISA法检测血浆去甲肾上腺素(NE)和血管升压素(AVP)水平,化学发光法测定室旁核超氧阴离子水平和NADPH氧化酶活性,Western Blot方法分析室旁核AT1R及NADPH氧化酶亚基p67phox、p47phox和gp91phox表达。结果与CON组比较,M组大鼠的平均动脉压显著升高,肾交感神经放电活动增加(P<0.01),压力反射敏感性指数降低(P<0.01),血浆NE和AVP水平均升高(P<0.01),室旁核超氧阴离子水平和NADPH氧化酶活性均增加(P<0.01),室旁核AT1R、gp91phox、和p47phox的蛋白表达增高(P<0.01)。与M组比较,DH、DL组大鼠的平均动脉压降低(P<0.05),肾交感神经放电活动减弱(P<0.05),压力反射敏感性指数升高(P<0.01,P<0.05),血浆NE和AVP水平下降(P<0.05),室旁核超氧阴离子水平和NADPH氧化酶活性均显著降低(P<0.05),以及室旁核AT1R、gp91phox和p47phox的蛋白表达显著下调(P<0.05)。结论大川芎方可以降低AngⅡ诱导高血压模型的动脉血压,抑制交感神经活性,改善压力反射敏感性,并下调下丘脑内AT1RNADPH氧化酶的异常表达和功能活性。

Objective To observe the effects of Dachuanxiong Decoction(DCXD)on abnormal sympathetic activities,baroreflex sensitivity and paraventricular nucleus(PVN)AngⅡtype 1 receptor(AT1R)-nicotinamide adenine dinucleotide phosphate(NADPH)oxidase pathway in hypertensive rats induced by angiotensinⅡ.Methods The hypertensive model was established in male SD rats by chronic angiotensinⅡperfusion with implantation of Alzet osmotic pump and high salt diet.The rats were randomly divided into control group(CON),model group(M),model+DCXD high-dose group(DH),model+DCXD low-dose group(DL)and model+losartan group(L),9 in each group.Artery blood pressure was measured by noninvasive blood pressure system in conscious rats.Renal sympathetic activity was recorded by electrophysiological methods,and baroreflex sensitivity was evaluated by Smyth method.The plasma levels of norepinephrine(NE)and vasopressin(AVP)were detected by ELISA.Superoxide anion level and NADPH oxidase activity in paraventricular nucleus were determined by Chemiluminescence.Western Blot was used to analyze the expression of AT1R,p67phox,p47phox and gp91phox in PVN.Results Compared with CON group,in M group the mean arterial pressure and renal sympathetic nerve activity increased significantly(P<0.01),the baroreflex sensitivity index decreased(P<0.01),the plasma NE and AVP levels increased(P<0.01),the superoxide anion level and NADPH oxidase activity in PVN increased(P<0.01),and the protein expressions of AT1R,gp91phox and p47phox increased(P<0.01).Compared with M group,in DH and DL groups the mean arterial pressure decreased(P<0.05),the renal sympathetic nerve discharge activity reduced(P<0.05),the baroreflex sensitivity increased(P<0.01,P<0.05),plasma NE and AVP levels decreased(P<0.05),the superoxide anion level and NADPH oxidase activity in PVN decreased(P<0.05),and the protein expressions of AT1R,gp91phox and p47phox down-regulated(P<0.05).Conclusion DCXD can reduce the arterial blood pressure,inhibit the sympathetic nerve activity,improve the baroreflex sensitivity,and decrease the abnormal expression and functional activity of AT1R-NADPH oxidase in hypothalamus.