目的 探讨青藤碱调控Toll样受体4（TLR4）/NADPH氧化酶4（NOX4）信号通路对心房颤动大鼠炎症反应及心肌纤维化的影响。方法 将SD大鼠随机分为对照组、模型组、青藤碱（20、40、80 mg/kg）组、维拉帕米组及青藤碱＋Pam3Cys组，每组12只。对照组大鼠通过舌下iv等量的生理盐水以代替心房颤动诱导液；其余各组大鼠均通过舌下iv心房颤动诱导液构建心房颤动大鼠模型，建模成功后，进行给药处理，1次/d，持续2周。彩色多普勒超声仪检测大鼠左室射血分数（LVEF）、左室短轴缩短率（LVFS）的变化；ELISA法检测大鼠血清中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平；检测大鼠左心室质量指数；苏木精–伊红（HE）染色检测大鼠心肌组织病理变化；Masson染色检测大鼠心肌组织纤维化程度；qRT-PCR检测左心室心肌组织中转化生长因子-β1（TGF-β1）、胶原蛋白Ⅰ型（Collagen-Ⅰ）mRNA表达；Western blotting检测大鼠左心室心肌组织中TLR4、NOX4蛋白表达。结果 与模型组比较，青藤碱各剂量组大鼠心肌组织病理损伤及心肌纤维化程度有所改善，LVEF、LVFS显著升高，IL-6、TNF-α水平，TGF-β1和Collagen-Ⅰ mRNA表达及TLR4、NOX4蛋白表达降低（P＜0.05）。与青藤碱组比较，青藤碱＋Pam3Cys组大鼠心肌组织病理损伤及心肌纤维化加重，LVEF、LVFS显著降低，IL-6、TNF-α水平，TGF-β1和Collagen-Ⅰ mRNA表达及TLR4、NOX4蛋白表达显著升高（P＜0.05）。结论 青藤碱可能通过抑制TLR4/NOX4通路抑制心房颤动大鼠炎症反应及心肌纤维化。

Objective To investigate the effect of sinomenine on inflammatory response and myocardial fibrosis in rats with atrial fibrillation by regulating the Toll-like receptor 4 (TLR4)/NADPH oxidase 4 (NOX4) signaling pathway. Methods SD rats were randomly grouped into control group, model group, sinomenine (20、40、80 mg/kg) group, verapamil group, and sinomenine + Pam3Cys group, with 12 rats in each group. Rats in control group was injected with an equal amount of physiological saline through the sublingual vein instead of atrial fibrillation inducing fluid, rats in other groups were used to construct atrial fibrillation rat models by injecting atrial fibrillation inducing fluid into the sublingual vein. After successful modeling, medication was administered once daily for 2 weeks. Color doppler ultrasound was applied to detect changes in left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) in rats. ELISA method was applied to detect the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rat serum. The left ventricular mass index of rats was detected, HE staining was applied to detect pathological changes in rat myocardial tissue, Masson staining was applied to detect the degree of myocardial fibrosis in rats, qRT-PCR was applied to detect the expression of transforming growth factor-β1 (TGF-β1) and Collagen-I mRNA in left ventricular myocardial tissue. Western blotting was applied to detect the expression of TLR4 and NOX4 proteins in rat left ventricular myocardial tissue. Results Compared with the model group, the myocardial tissue pathological damage and severe myocardial fibrosis of rats in sinomenine group were improved, LVEF and LVFS were increased, the IL-6 and TNF-α levels, TGF-β1 and Collagen-Ⅰ mRNA expression, and TLR4, NOX4 protein expression were reduced (P < 0.05). Compared with sinomenine group, the myocardial tissue pathological damage and myocardial fibrosis of rats in sinomenine + Pam3Cys group were aggravated, LVEF and LVFS were reduced, IL-6 and TNF-α levels, TGF-β1 and Collagen-Ⅰ mRNA expression, and TLR4, NOX4 protein expression were increased (P < 0.05). Conclusion Sinomenine may inhibit inflammatory response and myocardial fibrosis in rats with atrial fibrillation by inhibiting the TLR4/NOX4 pathway.

R285；R286.2

山东省中医药科技发展计划项目（2019-0034）