目的 探讨贝母素乙（PMI）调节鞘氨醇激酶 1（SphK1）/鞘氨醇-1-磷酸（S1P）信号通路对心房颤动（简称 房颤）大鼠心肌纤维化的影响。方法 构建房颤大鼠模型，将建模成功的大鼠分为房颤模型组，低剂量贝母素 乙及高剂量贝母素乙组（分别腹腔注射 2、5 mg·kg-1贝母素乙），贝母素乙+PMA 组（腹腔注射 5 mg·kg-1贝母素 乙+100 mg·kg-1 SphK1 激活剂 PMA），每组各 10 只，另选择 10 只正常大鼠作为对照组，房颤模型组和对照组注 射等量生理盐水。电子心电图记录房颤持续时间；超声心动图检测房颤大鼠心功能；Masson 染色检测房颤大鼠 心肌组织纤维化；ELISA 法检测房颤大鼠血清中 TGFβ1、activin A、collagen I、collagen III 表达；Western Blot 法检测大鼠心脏组织中 SphK1、S1P 蛋白的表达。结果 对照组心肌细胞排列整齐；房颤模型组心肌细胞排列紊 乱、胶原纤维较多，房颤持续时间、LAD、TGFβ1、activin A、collagen I、collagen III、SphK1、S1P 蛋白表达高 于对照组，LVEF、LVFS 低于对照组（P＜0.05）；低、高剂量贝母素乙组心肌细胞排列稍有紊乱，可见少量纤维， 房颤持续时间、LAD、TGFβ1、activin A、collagen I、collagen III、SphK1、S1P 蛋白表达低于房颤模型组， LVEF、LVFS 高于房颤模型组（P＜0.05）；贝母素乙+PMA 组心肌细胞排列进一步紊乱，纤维增多，房颤持续 时间、LAD、TGFβ1、activin A、collagen I、collagen III、SphK1、S1P 蛋白表达高于高剂量贝母素乙组， LVEF、LVFS 低于高剂量贝母素乙组（P＜0.05）。结论 贝母素乙可以抑制房颤大鼠心肌纤维化，其机制可能 是通过抑制 SphK1/S1P 信号通路实现的。

Objective To investigate the effect of peiminine B（PMI）on myocardial fibrosis in atrial fibrillation（AF）rats by regulating the sphingosine kinase 1（SphK1）/sphingosine-1-phosphate（S1P）signaling pathway. Methods An AF rat model was constructed，then successfully modeled rats were divided into AF group，low-dose peiminine B（L-PMI） group， high-dose peiminine B（H-PMI）group（intraperitoneal injection of 2 and 5 mg·kg-1PMI）， and PMI+PMA group（intraperitoneal injection of 5 mg·kg-1 PMI+100 mg·kg-1 SphK1 activator PMA），with 10 rats in each group. Another 10 rats were included as the control group. The AF group and the control group were injected with equal amounts of physiological saline. Electronic electrocardiogram was applied to record the duration of AF. Echocardiography was applied to detect cardiac function in AF rats. Masson staining was applied to detect myocardial fibrosis in AF rats. ELISA was applied to detect the expression of TGFβ1， activin A， collagen I， and collagen III in the serum of AF rats. Western Blot was applied to detect the expression of SphK1 and S1P proteins in heart tissue of rat. Results The myocardial cells in the control group were arranged neatly，but the arrangement of myocardial cells in the AF group was disordered and there were many collagen fibers， the duration of AF， and the protein expression of LAD， TGFβ1， activin A，collagen I，collagen III，SphK1，and S1P were higher than those in the control group，the LVEF and LVFS were lower than those of the control group（P＜0.05）. The arrangement of myocardial cells in the L-PMI and HPMI groups was slightly disordered，as well as a small amount of fibers were visible. The duration of AF and the protein expression of LAD，TGFβ1，activin A，collagen I，collagen III，SphK1，and S1P were lower than those in the AF group，the LVEF and LVFS were higher than those of AF group（P＜0.05）. The myocardial cell arrangement in the PMI+PMA group was further disrupted，with increased fibrosis. The duration of AF and the protein expression of LAD， TGFβ1， activin A， collagen I， collagen III， SphK1， and S1P were higher than those in the H-PMI group， the LVEF and LVFS were lower than those of H-PMI group（P＜0.05）. Conclusion PMI can inhibit myocardial fibrosis in AF rats. Its mechanism may be achieved by inhibiting the SphK1/S1P signaling pathway.

R285.5

河南省教育厅高等教育教学改革研究与实践项目（2024SJGLX0839）；信阳市科学技术局重点研发与推广项目（20230041）