吴茱萸次碱对腹主动脉缩窄大鼠左室肥厚的抑制作用  

Inhibitory Effect of Rutaecarpine on Left Ventricular Hypertrophy Rat Model Induced by Abdominal Aorta Coarctation

作　　者：张婧怡[1,2] 林淑娴[1,3] 李利生[1] 吴芹[1] 孙安盛[1] 

机构地区：[1]遵义医学院药理学教研室贵州省基础药理重点实验室,遵义563099 [2]山东省潍坊市人民医院药剂科,潍坊261041 [3]贵州省肿瘤医院药剂科,贵阳550001

出　　处：《医药导报》2018年第2期152-156,共5页Herald of Medicine

基　　金：国家自然科学基金资助项目(81160528)

摘　　要：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(P<0.01),伴左室压力上升或下降最大速率(±dp/dt_(max))显著降低(P<0.01),心肌病理学损伤和ANF mRNA表达的明显增加(P<0.01)。与模型对照组比较,Rut中、大剂量组腹主动脉缩窄大鼠的LWHI明显降低(P<0.05)、左室收缩压(LVSP)和左室舒张期末压(LVEDP)明显降低(P<0.05),±dp/dt_(max)升高(P<0.01)。Rut中、大剂量还能下调ANF、ERK2 mRNA和ERK2蛋白的表达,上调MKP-1 mRNA和蛋白的表达。与模型对照组比较,Rut小剂量组大鼠各项检测指标则无明显变化(P>0.05)。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。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 < 0.01),the decreased ± dp/dt_(max)(P<0.01),and the elevated expression of ANF(P<0.01).Compared with model control,Rut(20,40 mg·kg^(-1)·d^(-1)) treatment significantly attenuated AAC-induced rat left ventricular hypertrophy,decreased the LVHI(P < 0.05),left ventricular systole pressure(LVSP),and left ventricular end diastolic pressure(LVEDP)(P < 0.05),and increased ± dp/dt_(max)(P < 0.01).In addition,Rut(20,40 mg·kg^(-1)·d^(-1)) downregulated the expression of ANF,ERK2 mRNA,and ERK2 protein,but upregulated the MKP-1 mRNA and protein expression.However,Rut low-dose(10 mg · kg^(-1)·d^(-1)) was ineffective(P> 0.05).Conclu

关 键 词：吴茱萸次碱 左室肥厚 腹主动脉狭窄 细胞外信号调节激酶2 

分 类 号：R965[医药卫生—药理学]