养心定悸胶囊对异丙肾上腺素诱导SD大鼠缺血性心律失常的拮抗作用及机制

Antagonistic Effect and Mechanism of Yangxin Dingji Capsule(养心定悸胶囊)on Isoproterenol-induced Ischemic Arrhythmia in SD Rats

目的探讨养心定悸胶囊对缺血性心律失常的拮抗作用及机制。方法 60只健康雄性SD大鼠随机分为6组:对照组,模型组,普萘洛尔组和养心定悸低、中、高剂量组。异丙肾上腺素(isoproterenol, ISO)注射诱导缺血性心律失常。各组大鼠灌胃给药,1次/d,连续7 d,普萘洛尔组给予普萘洛尔15 mg·kg^(-1)·d^(-1);养心定悸低、中、高剂量组分别给予养心定悸胶囊0.5、1、2 g·kg^(-1)·d^(-1);对照组和模型组给予0.9%氯化钠溶液。采用BL-420F系统记录大鼠心电图变化;采用HE、Masson、TTC染色观察心肌组织病理损伤情况;采用ELISA测血清肌钙蛋白(cTnI)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平;采用自动生化仪测血清丙二醛(MDA)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)水平。结果与对照组比较,模型组大鼠室早及室速频发,心电图ST段抬高,心律失常评分增加(P<0.01);心脏指数(HWI)增加(P<0.01);心肌组织缺血损伤及病理损伤明显;氧化应激指标变化明显(P<0.01);血清炎症因子水平多升高(P<0.01或P<0.05)。与模型组比较,普萘洛尔组及养心定悸组大鼠发生室早及室速时间延迟、频次降低,心电图ST段抬高幅度减轻,心律失常评分降低(P<0.05);HWI降低(P<0.01);心肌组织病理损伤减轻;缺血损伤面积减小;血清cTnI降低(P<0.01或P<0.05);氧化应激状态改善(MDA水平降低而SOD、GSH升高)(P<0.01或P<0.05);血清炎症因子(TNF-α、IL-6等)水平降低(P<0.01或P<0.05)。结论养心定悸胶囊可以有效改善ISO诱导大鼠缺血性心律失常,其作用机制与其抑制氧化应激和炎症反应从而减轻心肌细胞损伤有关。

Objective To explore the antagonistic effect and mechanism of Yangxin Dingji Capsule(养心定悸胶囊)on ischemic arrhythmia.Methods Sixty healthy male SD rats were randomly divided into control group,model group,propranolol group and Yangxin Dingji groups(low dose,medium dose,and high dose).Isoprenaline(ISO)Injection induced ischemic arrhythmia model.Rats in each group were given intragastric administration once a day for 7 consecutive days.The propranolol group was given propranolol 15 mg·kg^(-1)·d^(-1).The low,medium and high dose groups of Yangxin Dingji Capsule were respectively given the corresponding doses(0.5,1,2 g·kg^(-1)·d^(-1)).The control group and the model group were given 0.9%sodium chloride.The ECG was recorded by BL-420 F system.The pathological changes of myocardial tissue were observed by HE and Masson staining.Serum levels of cardiac troponin I(cTnI),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and Interleukin-1β(IL-1β)were detected by ELISA.Serum levels of malondialdehyde(MDA),superoxide dismutase(SOD)and reduced glutathione(GSH)were detected by an automatic biochemical analyser.Results Compared with those of the control group,ventricular premature beats and ventricular tachycardia occurred frequently in the model group.ST segment of ECG and arrhythmia score were increased(P<0.01).Heart weight index(HWI)was increased(P<0.01).Myocardial ischemia injury and pathological injury were obvious.The changes of oxidative stress indexes were obvious(P<0.01)and the levels of serum inflammatory factors were mostly increased(P<0.01 or P<0.05).Compared with those of the model group,the occurrence time and frequency of ventricular premature beats and ventricular tachycardia in propranolol group and Yangxin Dingji Capsule groups were delayed and decreased.ST segment elevation,arrhythmia score and HWI were decreased(P<0.05 or P<0.01).The pathological damage of myocardial tissue and the area of ischemic damage were reduced.Serum cTnI was decreased(P<0.01 or P<0.05).The oxidative stress state was improved.MDA level decreased while SOD and GSH increased(P<0.01 or P<0.05).The levels of serum inflammatory factors(TNF-α,IL-6)were decreased(P<0.01 or P<0.05).Conclusions Yangxin Dingji Capsule can effectively improve ISO-induced ischemic arrhythmia in rats,and its mechanism of action is related to its inhibition of oxidative stress and inflammatory response to reduce myocardial cell damage.