目的 基于miR-26a-5p/WNT5A信号通路探讨天麻素防治阵发性房颤大鼠的作用机制。方法 大鼠随机分为对照组、模型组、天麻素（16.665、66.660 mg/kg）组、胺碘酮组、天麻素＋inhibitor NC组、天麻素＋miR-26a-5p inhibitor组，每组12只。检测房颤诱发时间、房颤持续时间、左心室分数缩短（LVFS）、左心室射血分数（LVEF）、左心房直径、左心房面积的变化；Masson染色检测心房肌组织纤维化；免疫组化染色检测心房肌组织α-平滑肌肌动蛋白（α-SMA）、I型胶原（Collagen I）阳性表达面积；qRT-PCR检测心房肌组织miR-26a-5p水平；Western blotting检测心房肌组织WNT5A表达。结果 与模型组比较，天麻素组心房肌组织纤维化程度减轻，房颤诱发时间延长，房颤持续时间缩短，LVFS、LVEF增加，左心房直径、左心房面积减少，心房肌组织中miR-26a-5p水平升高，α-SMA、Collagen I阳性表达面积及WNT5A表达降低（P＜0.05）。miR-26a-5p inhibitor逆转了天麻素对阵发性房颤大鼠心房结构重构及心房肌组织纤维化的抑制作用。结论 天麻素可抑制阵发性房颤大鼠心房结构重构及心房肌组织纤维化，该机制可能与上调miR-26a-5p、抑制WNT5A表达有关。

Objective To explore the mechanism of gastrodin in preventing and treating paroxysmal atrial fibrillation in rats model based on miR-26a-5p/WNT5A signaling pathway. Methods Rats were randomly divided into control group, model group, gastrodin (16.665、66.660 mg/kg) group, amiodarone group, gastrodin + inhibitor NC group, and gastrodin + miR-26a-5p inhibitor group, with 12 rats in each group. The induction time and duration of atrial fibrillation, LVFS, LVEF, left atrial diameter, left atrial area were detected in each group. Atrial muscle tissue fibrosis was detected by Masson staining. Immunohistochemical staining was used to indicate positive expression area of α-SMA and Collagen I in atrial muscle tissue. The level of miR-26a-5p in atrial muscle tissue was measured by qRT-PCR. Western blotting was used to detect the WNT5A experssion in atrial muscle tissue. Results Compared with the model group, the degree of atrial muscle tissue fibrosis in the gastrodin group was alleviated, the induction time of atrial fibrillation was prolonged, the duration of atrial fibrillation was shortened, LVFS and LVEF were increased, and the left atrial diameter and left atrial area were decreased (P < 0.05). The level of miR-26a-5p was significantly increased, while positive expression area of α-SMA and Collagen I positive cells was decreased, and the expression of WNT5A was also decreased in atrial muscle tissue (P < 0.05). miR-26a-5p inhibitor reversed the inhibitory effect of gastrodin on atrial structural remodeling and atrial muscle tissue fibrosis in paroxysmal atrial fibrillation rats. Conclusion Gastrodin can inhibit atrial structural remodeling and atrial muscle tissue fibrosis in rats with paroxysmal atrial fibrillation, which may be related to the upregulation of miR-26a-5p and the downregulation of WNT5A expression.

R285.5;R286.2

河南省医学科技攻关计划联合共建项目（LHGJ20230738）