三七皂苷预防异丙肾上腺素所诱导小鼠阵发性房颤发生的机制研究

Panax Notoginseng Saponins Prevent Against Isoproterenol-induced Atrial Fibrillation in C57BL/6 Mouse:a Mechanism Study

探索三七皂苷(PNS)预防大剂量异丙肾上腺素(ISO)所诱导小鼠阵发性房颤发生的作用机制。方法 54只C57BL/6雄性随机分为正常对照组、模型组和治疗组。以大剂量ISO腹腔注射诱导阵发性房颤的发生,治疗组于造模前0.5h腹腔注射PNS,正常对照组则分别给予等体积的生理盐水。各组随机选取6只,监测房颤发生情况;余实验动物分别于造模1.5h后,取其心脏组织,通过HE染色以及Annexin V荧光染料法以检测细胞凋亡情况;并进一步检测心房组织中miR-29b,miR-499,miR-210,miR-328的表达。结果模型组可见典型阵发性房颤的发生,治疗组未见房颤的发生;与模型组相比,PNS显著降低ISO所诱导心肌细胞凋亡情况(P<0.05);与正常组相比,模型组心房组织中miR-499及miR-210显著上调(P<0.05),miR-29b和miR-328的表达显著下调(P<0.05);与模型组相比,PNS显著下调心房组织中miR-499及miR-210的表达(P<0.05),显著上调miR-29b和miR-328的表达(P<0.05)。结论 PNS显著预防ISO所诱导小鼠阵发性房颤发生的作用机制,可能与其调节心肌组织中相关miRNAs的表达,改善心房电重构和结构重构有关。

Objective To provide experimental evidence supporting the clinical application of Panax Notoginseng Saponins（PNS）as an anti-arrhythmic agent.To evaluate the effect and the possible mechanism of PNS on isoproterenol（ISO）-induced atrial fibrillation in mouse.Methods Fifty-four C57 BL/6 male mice were randomly divided into experimental groups including vehicle-treated normal controls,ISO-challenged controls,and PNS-treated ISO-challenged mice,respectively.ISO was administered to vehicle-treated or PNS-treated mice 30 min after PBS vehicle or PNS treatment.The dynamic changes of electrocardiogram were monitored in each group（n =6）.And other mice were sacrificed 1.5 hours after ISO administration and the heart sections were measured by H＆E staining and Annexin V fluorescent dyes to detect apoptosis.Further,the expression of miR-29 b,miR-499,miR-210,and miR-328 in the mice heart were analyzed by real-time PCR.Results Compared to that from vehicle-treated ISO-challenged mice,the atrial fibrillation was significantly decreased in ISO-challenged mice treated by PNS.Moreover,compared to that from ISO-challenged mice treated by PBS vehicle,PNS treatment resulted in significant reductions in cell apoptosis.Furthermore,significantly upregulated expression of miR-499 and miR-210,and downregulated expression of miR-29 b and miR-328 was observed in heart in vehicle-treated ISO-challenged controls compared to that from normal controls.Compared to vehicle-treated ISO-challenged controls,the expression of miR-499 and miR-210 were significantly downregulated,and the expression of miR-29 b and miR-328 were significantly upregulated in PNS-treated ISO-challenged group.Conclusion Our work here demonstrated that PNS treatment prevent against isoproterenolinduced atrial fibrillation in C57 BL/6 mouse,and its mechanism might be possibly associate with regulating expression of miRNAs,then improving the atrial electrical remodeling and structural remodeling.