目的 探讨稳心颗粒对心律失常大鼠凋亡、炎症及氧化应激的影响。方法 60只雄性SD大鼠随机分为对照组、模型组及稳心颗粒低、中、高剂量（1.34、2.68、5.36 g/kg）组和胺碘酮（35.7 mg/kg）组。各组大鼠连续预防性给药21 d，对照组和模型组ig纯水。末次给药后1 h将大鼠麻醉，尾iv乌头碱以诱导心律失常。采用多道生理信号采集处理系统记录大鼠注射乌头碱前后的心电图变化；采用苏木素-伊红（HE）、Masson染色观察心肌组织病理损伤情况；TUNEL染色观察心肌细胞凋亡情况；采用试剂盒检测血清中超氧化物歧化酶（superoxide dismutase，SOD）活性及丙二醛（malonaldehyde，MDA）、还原型谷胱甘肽（glutathione，GSH）、白细胞介素-18（interleukin-18，IL-18）、IL-1β、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平；采用Western blotting检测心肌组织兰尼碱受体2（ryanodine receptor 2，RYR2）、NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）、Toll样受体4（Toll-like receptor 4，TLR4）以及B淋巴细胞瘤-2（B-cell lymphoma-2，Bcl-2）、Bcl-2相关X蛋白（Bcl-2 associated X protein，Bax）表达。结果 与对照组比较，模型组大鼠室早及室速频发，心律失常评分增加（P＜0.01），心肌组织病理损伤及细胞凋亡情况明显，血清氧化应激指标（SOD、MDA）变化明显（P＜0.01）；血清炎症因子水平均显著升高（P＜0.01），心肌组织RYR2、NLRP3、TLR4、Bax蛋白表达水平显著升高（P＜0.01），Bcl-2蛋白表达水平显著降低（P＜0.01）。与模型组比较，胺碘酮组及稳心颗粒高剂量组大鼠心律失常持续时间缩短，心律失常评分降低（P＜0.05、0.01）；心肌组织病理损伤减轻，心肌细胞凋亡指数降低；氧化应激状态（SOD、MDA）改善（P＜0.05、0.01）；血清炎症因子水平降低（P＜0.05、0.01）；离子通道蛋白RYR2表达降低（P＜0.01），炎症相关蛋白NLRP3、TLR4表达降低（P＜0.01），凋亡蛋白Bax表达降低（P＜0.01），抗凋亡蛋白Bcl-2表达升高（P＜0.01）。结论 稳心颗粒可以有效改善乌头碱所诱导的大鼠心律失常，其作用机制可能与抑制氧化应激和炎症反应、降低凋亡水平从而减轻心肌细胞损伤有关。

Objective To investigate the effect of Wenxin Granules (稳心颗粒) on apoptosis, inflammation and oxidative stress in arrhythmia rats. Methods A total of 60 male SD rats were randomly divided into control group, model group, Wenxin Granules low-, medium- and high-dose (1.34, 2.68, 5.36 g/kg) groups and amiodarone (35.7 mg/kg) group. Each group was given prophylactic medication continuously for 21 d, while the control group and model group were given pure water. 1 h after the last administration, the rats were anesthetized, and aconitine was injected into the tail vein to induce arrhythmia. Multi-channel physiological signal acquisition and processing system was used to record the electrocardiogram changes of rats before and after injection of aconitine; Hematoxylin eosin (HE) and Masson staining were used to observe the pathological damage of myocardial tissue; TUNEL staining was used to observe the apoptosis of myocardial cells; Kits were used to detect the activity of superoxide dismutase (SOD) and levels of malondialdehyde (MDA), reduced glutathione (GSH), interleukin-18 (IL-18), IL-1β and tumor necrosis factor-α (TNF-α) in serum; Western blotting was used to detect the expressions of ryanodine receptor 2 (RYR2), NOD like receptor thermal protein domain associated protein 3 (NLRP3), Toll-like receptor 4 (TLR4), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in myocardial tissue. Results Compared with control group, ventricular premature and ventricular tachycardia occurred frequently in model group, and arrhythmia score was increased (P < 0.01). The pathological injury and apoptosis of myocardial tissue were obvious. The oxidative stress indexes (SOD and MDA) in serum were significantly changed (P < 0.01). The levels of inflammatory factors in serum were increased (P < 0.01). The expressions of RYR2, NLRP3, TLR4 and Bax in myocardial tissue were increased (P < 0.01), while the expression of Bcl-2 was decreased (P < 0.01). Compared with model group, the duration of arrhythmia in amiodarone group and Wenxin Granules high-dose group were shortened, and the arrhythmia score was decreased (P < 0.05, 0.01). The pathological injury of myocardium was alleviated, and the apoptosis index of myocardium was decreased. The state of oxidative stress (SOD, MDA) were improved (P <0.05, 0.01). Levels of inflammatory cytokines in serum were decreased (P < 0.05, 0.01). The expressions of RYR2, NLRP3 and TLR4 were decreased (P < 0.01), the expression of apoptosis protein Bax was decreased (P < 0.01), and the expression of anti-apoptosis protein Bcl-2 was increased (P < 0.01). Conclusion Wenxin Granules can effectively ameliorate the arrhythmia induced by aconitine in rats, and its mechanism may be related to inhibiting oxidative stress and inflammation, reducing apoptosis level and thus alleviating myocardial cell damage.

国家自然科学基金资助项目（82004329）；天津市教委科研计划项目（2019SK025）；国家中医药管理局全国名老中医药专家传承工作室建设项目“杜武勋全国名老中医药专家传承工作室”；天津市中医药管理局天津市名中医传承工作建设项目“杜武勋天津市名中医传承工作室”