吴茱萸次碱对腹主动脉缩窄大鼠左室肥厚的抑制作用

摘要

Objective To investigate the inhibition of rutaecarpine (Rut) on left ventricular hypertrophy rat induced by abdominal aorta coarctation (AAC) and further explore the potential mechanisms. Methods Left ventricular hypertrophy was induced by AAC in male Sprague-Dawley rats.Fifty rats were randomly divided into five groups:model control group,sham operation group,low-,middle- and high-dose (10,20,40 mg?kg-1?d-1 ) Rut group,with 10 rats of each group.Rut was administrated by gavage once daily from the first day after operation for consecutive 4 weeks.The sham operation and model groups were administrated with equal volume of 0.9％ sodium chloride solution.The hemodynamics parameters were detected by BL-420 E biology function laboratory system,and the left ventricular hypertrophy index (LVHI,left ventricular weight/ body weight) was measured at 8 h after administration of the last dose.The pathological changes of left ventricular hypertrophy were evaluated by HE staining.To elucidate the mechanism of protection,the mRNA expressions of atrial natriuretic factor ( ANF),extracellular signal-regulated kinase 2 (ERK2) and MAPK phosphatase-1 (MKP-1) were analyzed by real time RT-PCR,and the protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. Results Left ventricular hypertrophy induced by AAC was evidenced by the increased left ventricular weight (LVW) and LVHI (P 0.05). Conclusion Rut alleviates left ventricular hypertrophy induced by abdominal aorta coarctation,and the protection appears to be due,at least in part,to its inhibitory effects on the MAPK/ ERK signal pathway.%目的 研究吴茱萸次碱(Rut)对腹主动脉缩窄(AAC)大鼠左室肥厚的抑制作用及其可能的机制.方法采用雄性SD大鼠制备腹主动脉缩窄左室肥厚模型,50只大鼠随机分为5组:假手术组、模型对照组和Rut小、中、大(10,20,40 mg?kg-1?d-1)剂量组,每组10只.于造模手术次日,Rut灌胃给药,连续4周,假手术和模型组灌胃等容量0.9％氯化钠溶液.最后一次给药后8 h,BL-420 E生物机能实验系统测量大鼠左心室血流动力学,记录大鼠体质量(BW),测量左室质量(LVW),计算左室肥厚指数(LWHI),行病理切片苏木精-伊红(HE)染色,观察心肌形态学的改变.实时反转录-聚合酶链反应(RT-PCR)检测大鼠心房利钠因子(ANF)、细胞外信号调节激酶2(ERK2)和丝裂素活化蛋白激酶磷酸酶-1(MKP-1)mRNA的表达,Western blotting检测MKP-1和p-ERK2的蛋白表达.结果与假手术组比较,模型对照组LVW和LWHI明显增加(P0.05).结论Rut能明显防治大鼠腹主动脉缩窄所致左室肥厚,其作用机制至少部分与其抑制MAPK/ERK信号通路有关.