基于“心脑同治”理论研究佛手养心汤改善气虚血瘀型心衰后认知障碍模型大鼠心肌线粒体损伤的作用

Research on the Effect of Foshou Yangxin Decoction on Improving Cognitive Impairment Model of Rat Myocardial Mitochondrial Damage in Qi Deficiency and Blood Stasis Heart Failure Based on the Theory of“Heart and Brain Treatment”

目的:基于“心脑同治”理论探索佛手养心汤对气虚血瘀型心衰后认知障碍模型大鼠的影响,及对心肌线粒体结构与能量代谢损伤的改善作用。方法:通过体内实验,将48只SD大鼠随机选取10只作为正常组,剩余大鼠予以异丙肾上腺素腹腔注射、左旋硝基精氨酸灌胃以建立心衰后认知障碍模型,然后采取饥饿法和力竭游泳法以建立气虚血瘀型模型。将造模成功后的大鼠随机分为模型组、治疗组和对照组,每组10只。正常组和模型组大鼠常规饲养,治疗组予以佛手养心汤干预,对照组予以盐酸曲美他嗪片干预,为期4周。观察大鼠的一般情况,运用动物心脏超声仪检测大鼠心脏LVESD、LVEDD、LVEF指标;Morris水迷宫检测认知功能;透射电镜下观察心肌线粒体结构改变;比色法检测心肌线粒体mPTP开放程度;微量法检测心肌组织ATP含量。结果:造模成功后大鼠一般情况差,反应迟钝,皮肤和毛发枯燥无光泽,活动减少,进食缓慢,饮水量减少,唇甲发绀,部分大鼠出现气促而喘的症状。造模结束予以药物干预后,大鼠上述表现可明显改善。心动超声检测提示模型组大鼠LVESD、LVEDD明显增厚,LVEF明显降低,而治疗组、对照组可显著逆转上述变化。Morris水迷宫检测显示模型组大鼠逃避潜伏期明显延长,且穿越平台次数明显减少,而治疗组与对照组检测结果与之相反。与此同时,以透射电镜观察线粒体结构、比色法与微量法检测线粒体能量代谢状态,发现模型组大鼠线粒体结构损伤明显,线粒体mPTP开放程度显著增加,心肌组织ATP含量明显降低,而治疗组与对照组给予相应药物干预后可显著逆转上述改变。结论:佛手养心汤可有效抑制心衰大鼠心肌线粒体mPTP开放,改善线粒体结构损伤,增加心肌组织ATP含量,逆转心功能改变,从而改善气虚血瘀型心衰后认知障碍大鼠的线粒体功能和认知功能。

Objective:To explore the effect of Foshou Yangxin Decoction on cognitive impairment model rats with heart failure due to Qi deficiency and blood stasis based on the theory of“heart and brain treatment”,and its improvement effect on myocardial mitochondrial structure and energy metabolism damage.Methods:Through in vivo experiments,10 of 48 SD rats were randomly selected as the normal group,and the remaining rats were given intraperitoneal injection of isoproterenol and intragastric administration of L-nitroarginine to establish a cognitive impairment model after heart failure.The starvation method and exhaustive swimming method were adopted to establish the Qi deficiency and blood stasis model.The rats after successful modeling were randomly divided into model group,treatment group and control group,with 10 rats in each group.The rats in the normal group and the model group were fed conventionally.The treatment group was treated with Foshou Yangxin Decoction,and the control group was treated with trimetazidine hydrochloride tablets for a period of 4 weeks.Observe the general condition of the rats,use an animal cardiac ultrasound instrument to detect the LVESD,LVEDD,and LVEF indicators of the rat's heart;Morris water maze to detect cognitive function;observe the structural changes of myocardial mitochondria under a transmission electron microscope;and detect the degree of mPTP opening of myocardial mitochondria using a colorimetric method;Detection of ATP content in myocardial tissue using micro-method.Results:After successful modeling,the general condition of the rats was poor,with slow reaction,dull skin and hair,reduced activity,slow eating,reduced water drinking,cyanotic lip nails,and some rats developed symptoms of shortness of breath and wheezing.After drug intervention was given at the end of the modeling period,the above-mentioned performance of the rats could be significantly improved.Cardiac ultrasound examination showed that the LVESD and LVEDD of rats in the model group were significantly thickened,and the LVEF was significantly reduced,while the treatment group and control group could significantly reverse the above changes.Morris water maze test showed that the escape latency of rats in the model group was significantly prolonged,and the number of times they crossed the platform was significantly reduced,while the test results of the treatment group and the control group were opposite.At the same time,the mitochondrial structure was observed with transmission electron microscopy,and the energy metabolism status of mitochondria was detected by colorimetry and micromethods.It was found that the mitochondrial structure of rats in the model group was significantly damaged,the degree of mitochondrial mPTP opening was significantly increased,and the ATP content of myocardial tissue was significantly reduced,while the treatment group was compared with The above changes can be significantly reversed after the control group is given corresponding drug intervention.Conclusion:Foshou Yangxin Decoction can effectively inhibit the opening of myocardial mitochondrial mPTP in heart failure rats,improve mitochondrial structural damage,increase ATP content in myocardial tissue,reverse changes in cardiac function,thereby improving mitochondrial function in rats with cognitive impairment after heart failure due to Qi deficiency and blood stasis.functional and cognitive functions.