苓桂术甘汤对肺动脉高压致右心衰大鼠心功能、神经内分泌因子水平及心脏组织NF-κB蛋白表达的影响

Study on Effect of Linggui Zhugan Decoction on Cardiac Function,Neuroendocrine Factors Levels and Regulation of NF-κB in Rats with Right Heart Failure Caused by MCT-Induced Pulmonary Hypertension

目的:探讨苓桂术甘汤对野百合碱所致肺源性心力衰竭大鼠的疗效及可能的作用机制。方法:将60只雄性SD大鼠随机分为空白对照组、模型组、呋塞米组及苓桂术甘汤高、低剂量组,每组12只。除空白对照组外,其余各组采用野百合碱诱导肺动脉高压致右心心力衰竭模型。苓桂术甘汤高、低剂量组给药剂量分别为12 g/(kg·d)和2.5 g/(kg·d),呋塞米组为20 mg/(kg·d),各组均以5 mL/(kg·d)蒸馏水稀释药液灌胃;模型组和空白对照组以等体积蒸馏水灌胃,1次/d,连续灌胃4周。记录各组大鼠一般情况,心脏指数,心脏超声心动图,血浆BNP,AVP,REN和AngⅡ水平,心脏病理切片HE染色,检测心脏组织NF-κB、TNF-α蛋白的表达。结果:模型组的大鼠心肌纤维出现自溶,肌纤维断裂排列紊乱,心肌细胞核固缩明显,甚至破裂消失,与模型组比较,药物干预各组病变均改善;与模型组比较,苓桂术甘汤高、低剂量组肺动脉压力(p)和肺动脉压力与速度比值(p/v)降低,同时肺动脉血流加速时间(PAAT)和加速时间与射血时间比值(PAAT/ET)显著升高;右心室内径减少,BNP,REN和AngⅡ、AVP水平和大鼠心脏组织NF-κB和TNF-α蛋白表达降低,且以苓桂术甘汤高剂量组的变化差异更为显著(P<0.05)。结论:苓桂术甘汤高剂量组可改善野百合碱诱导的肺动脉高压合并右心衰大鼠的心功能和病理组织改变,降低神经内分泌因子水平,其机制可能通过调节NF-κB介导的炎症信号通路以缓解慢性心衰的发展。

Objective:To investigate the efficacy and possible mechanism of Linggui Zhugan decoction in the treatment for MCT-induced pulmonary heart failure in rats.Methods:60 male SD rats were randomly divided into different groups,including blank control group,model group,furosemide group,Linggui Zhugan decoction high dose group and low dose group,with 12 rats in each group.Except the blank control group,the model of right ventricular heart failure was prepared by monocrotaline-induced pulmonary hypertension.The high dose and low dose groups were given 12(g/kg)·d and 2.5 g/(kg·d)of Linggui Zhugan decoction,seperately,and furosemide group was given 20 mg/(kg·d)of furosemide.All the medicines were diluted with distilled water according to 5 mL/(kg·d)and given by gavage once a day for 4 weeks.The model group and the blank control group were given the same volume of distilled water.General situation of each rat was observed.Cardiac index,heart echocardiography,BNP,AVP,Renin and AngiotensinⅡlevels in plasma,heart pathological HE staining,and the expression of NF-κB,TNF-αprotein in cardiac tissue were detected.Results:In the model group,the myocardial fibers of the rats presented autolysis,muscle fibers were broken,curled,and arranged in disorder.The nuclei of the myocardium were obviously contracted,and even ruptured.Compared with the model group,the lesions in each group of drug intervention were improved.Compared with the model group,the pulmonary artery pressure(p)and the ratio of pulmonary artery pressure to velocity(p/v)decreased in the Linggui Zhugan decoction high dose and low dose groups,while the pulmonary artery blood flow acceleration time(PAAT)and the ratio of acceleration time to ejection time(PAAT/ET)increased significantly.The right ventricular diameter,BNP,REN,AngII,and AVP levels in plasma and the expression of NF-κB and TNF-αprotein in cardiactissue decreased significantly.In addition,the differences of Linggui Zhugan decoction group high dose were more significant than those of the low dose group(P<0.05 or P<0.01).Conclusion:The Linggui Zhugan decoction high dose group could improve the cardiac function and reduce the level of neuroendocrine factors in rats withright heart failure caused by MCT-induced pulmonary hypertension.The mechanism of this effect may be related to NF-κB mediated inflammatory signaling pathway,leading to alleviate the development of chronic heart failure.