芪苈强心胶囊对慢性心衰大鼠认知功能障碍的影响及机制研究

Study on the Effect and Mechanism of Qili Qiangxin Capsule on Cognitive Dysfunction in Chronic Heart Failure Rats

目的 观察芪苈强心胶囊对慢性心(chronic heart failure,CHF)衰后认知功能障碍的干预作用并探讨其相关机制。方法 SD大鼠建立心梗后心衰大鼠模型,分为假手术组、模型组、芪苈组和缬沙坦组。Morris水迷宫检测大鼠认知功能,超声心动图和血流动力学检测心功能,HE染色观察心脏结构,尼氏染色观察海马神经元,ELISA法检测血浆和海马血管紧张素(angiotensin,Ang)Ⅱ、海马β淀粉样蛋白(amyloid-β,Aβ)42浓度。结果 与假手术组比较,模型组大鼠的左心室舒张末压(left ventricular end diastolic pressure,LVEDP)、海马Aβ42、血浆和海马AngⅡ浓度显著升高(P<0.05),穿台次数、心室射血分数(ejection fraction,EF)、心室缩短分数(fractional shortening,FS)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室内压最大上升速率(the maximal rate of increase of left ventricular pressure,+dp/dt max)和最大下降速率(the maximal rate of decrease of left ventricular pressure,-dp/dt max)显著降低(P<0.05),心肌细胞结构模糊,有明显炎性细胞浸润,海马神经元数量减少且染色较浅。与模型组比较,芪苈组大鼠的海马Aβ42、血浆和海马AngⅡ浓度明显降低(P<0.05),穿台次数、EF、FS、LVSP显著增加(P<0.05),心肌和海马染色结果均有改善。结论芪苈强心胶囊可能通过抑制外周和海马AngⅡ及脑内Aβ42水平,改善慢性心衰大鼠心功能和认知功能障碍。

Objective To observe the intervention effect of Qili Qiangxin capsule on cognitive dysfunction after chronic heart failure(CHF)and explore its related mechanism.Methods SD rats were used to establish the model of heart failure after myocardial infarction,then divided into sham group,model group,Qili group and valsartan group.Morris water maze was used to detect the cognitive ability of rats.Echocardiography and hemodynamics were used to detect the changes of cardiac function.HE staining was used to observe the changes of cardiac structure.Nissl staining was used to observe the changes of hippocampal neurons in rats.ELISA was used to detect the concentration of Angiotensin(Ang)Ⅱin plasma and hippocampal tissue and the concentration of Amyloid-β(Aβ)42 in hippocampal tissue.Results Compared with the sham group,left ventricular end diastolic pressure(LVEDP),Aβ42 concentration in hippocampus and AngⅡcontent in plasma and hippocampus was significantly increased in rats of model group(P<0.05),the number of crossing the platform,the ventricular ejection fraction(EF),fractional shortening(FS),the left ventricular and systolic pressure(LVSP),the maximal rate of increase of left ventricular pressure,(+dp/dt max),and the maximal rate of decrease of left ventricular pressure,(-dp/dt max)were significantly decreased in rats of model group(P<0.05),the structure of myocardial cells was fuzzy,and the number of hippocampal neurons decreased and the staining was shallow in rats of model group.Compared with the model group,the plasma and hippocampus levels of Aβ42 and AngⅡwere significantly decreased in rats of Qili group(P<0.05).While we observed the increasing number of crossing the platform,the ventricular ejection fraction,fractional shortening,and the left ventricular end systolic pressure increased(P<0.05),and the structure of heart and hippocampus was improved in rats of Qili group.Conclusion Qili Qiangxin capsule can improve cardiac function and cognitive dysfunction in rats with chronic heart failure.The specific mechanism may be related to the inhibition of peripheral and hippocampal AngⅡlevels and Aβ42 levels in the brain.