三七总皂苷防治异丙肾上腺素诱导的心肌损伤实验研究

Experimental Study on Panax notoginseng Saponins Attenuates Isoproterenol-induced Myocardial Injury

目的观察三七总皂苷(PNS)对异丙肾上腺素(ISO)诱导的心肌损伤的疗效,并探索三七总皂苷防治心肌损伤潜在的作用机制,为三七总皂苷防治心肌损伤的临床应用提供实验依据。方法将实验小鼠分为3组:正常对照组、ISO模型组、PNS治疗组。ISO造模7 d后,取心脏组织进行HE染色和Masson三色染色评估PNS对ISO诱导的心肌损伤的防治作用。进一步对心肌组织行RT-PCR检测miR-1和miR-222表达,通过免疫组化方法检测MET蛋白在心肌组织的表达。结果心脏病理染色显示,ISO诱导的心肌损伤模型组心肌细胞坏死、大量炎性细胞浸润、胶原纤维增多。而PNS治疗组心脏仅有少量,偶见的炎性细胞,胶原纤维阳性率较ISO模型组显著降低。在ISO模型组心脏中miR-1表达较正常对照组显著降低,miR-222表达显著升高。经PNS治疗后,与ISO模型组相比miR-1表达显著增高;而miR-222表达显著降低。免疫组化表明,MET在模型组心脏中表达显著升高且主要集中在损伤部位,而在PNS治疗组中显著降低。结论 PNS对ISO诱导的心肌损伤具有明显防治作用,miR-1/MET/miR-222信号通路可能参与ISO诱导心肌损伤的形成及PNS抗心肌损伤。

Objective To investigate the effect of panax notoginseng saponins （ PNS）on isoproterenal （ ISO） induced myocardial in -jury and explore the mechanism of PNS anti myocardial injury. Methods C57 mice were divided into vehicle control （ VC）group,ISO induced myocardial injury （ ISO）group, and PNS treatment （ PNS）group.All mice were intraperitoneally injected vehicle control,ISO, ISO, and PNS separately for 7 days. Heart was utilized for HE stain and massion trichrome stain were performed in heart to ac -cess the therapeutic effect of PNS on ISO induced myocardial injury.Further, real time PCR was carried out to detect the expres -sion of miR 1 and miR 222 in heart, and Met was probed in heart using immunohistochemical staining to discover the role of miR1/MET/miR 222 in the anti myocardial injury effect of PNS. Results The pathological staining showed that ISO induced myocardialinjuries including necrotic degeneration, granulation as well as inflammatory cell infiltration, and collagen accumulation which was in -variably observed in ISO challenged mice.Whereas, slight necrosis, sporadic infiltration of inflammatory cells and accumulation of col-lagen were observed in PNS treated mice.Down regulated expression of miR 1 and up regulated expression of miR 222 were dem -onstrated in heart from ISO induced myocardial injury mice compared to that from vehicle control mice.While expression of miR 1and miR 222 were rescued in heart from PNS treated mice.The level of MET was increased in heart from ISO challenged mice andit focused in the area of injury.But the positive stain of MET in heart from PNS treated mice was significantly less than that from ISOchallenged mice. Conclusion PNS has a dominantly therapic effect on ISO induced myocardial injury. MiR 1/MET/miR 222 axismay play an important role in the pathological process of myocardial injury induced by ISO and anti myocardial injury effect of PNS.