Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.
West China School of Medicine, Sichuan University, Chengdu, China.
Biomed Pharmacother. 2022 Oct;154:113573. doi: 10.1016/j.biopha.2022.113573. Epub 2022 Aug 18.
Although many research have found that colchicine has general therapeutic effect in cardiovascular disease, the therapeutic mechanism in atrial fibrillation has not been clearly studied. To explore whether colchicine plays a role in the treatment of AF by reducing myocardial fibrosis, we performed a series of studies. Rat models of AF were induced by Ach-CaCl to assess the therapeutic effect of colchicine at doses of 0.8 mg/kg on the duration of AF rhythm, degree of myocardial fibrosis, and secretion of inflammatory factors in the serum. RNA-Seq was also performed to elucidate the possible mechanisms by which colchicine might reduce the alleviation of myocardial fibrosis associated with AF. These studies showed that colchicine reduced the duration of AF and the degree of fibrosis in the left atrium and that it significantly reduced the secretion of TGFβ1, activin A, collagen I, and collagen III. These results suggest that colchicine may reduce myocardial fibrosis by (1) inhibiting the TGFβ1/ALK5 and activin A/ALK4 fibrosis pathways; (2) inhibiting the activation, phenotypic transformation, and apoptosis resistance of myocardial fibroblasts; and (3) reducing the synthesis of inflammatory factors and collagen.
尽管许多研究发现秋水仙碱在心血管疾病中有普遍的治疗作用，但在心房颤动中的治疗机制尚未得到明确研究。为了探讨秋水仙碱是否通过减少心肌纤维化来发挥治疗 AF 的作用，我们进行了一系列研究。用 Ach-CaCl 诱导 AF 大鼠模型，以评估秋水仙碱在 0.8mg/kg 剂量下对 AF 节律持续时间、心肌纤维化程度和血清中炎症因子分泌的治疗作用。还进行了 RNA-Seq 以阐明秋水仙碱可能减轻与 AF 相关的心肌纤维化缓解的可能机制。这些研究表明，秋水仙碱可缩短 AF 的持续时间和左心房的纤维化程度，显著降低 TGFβ1、激活素 A、胶原 I 和胶原 III 的分泌。这些结果表明，秋水仙碱可能通过以下机制减少心肌纤维化：（1）抑制 TGFβ1/ALK5 和激活素 A/ALK4 纤维化途径；（2）抑制心肌成纤维细胞的激活、表型转化和抗凋亡；（3）减少炎症因子和胶原的合成。
