吴茱萸总碱抑制大鼠左室肥厚及对钙调神经磷酸酶信号通路的影响  

Inhibition of Evodia total alkaloids on rat left hypertrophy:role of calcineurin signaling pathway

作　　者：张婧怡[1] 林淑娴[1] 侯化化[1] 李强[1] 徐洋[1] 孙安盛[1] 

机构地区：[1]遵义医学院药理学教研室暨贵州省基础药理重点实验室,贵州遵义563099

出　　处：《遵义医学院学报》2014年第2期151-155,共5页Journal of Zunyi Medical University

基　　金：国家自然科学基金项目(NO:81160528);贵州省中医药局项目(NO:黔中医药2009-79)

摘　　要：目的观察吴茱萸总碱对大鼠腹主动脉缩窄术后压力超负荷所致心肌肥厚的抑制作用,及对钙调神经磷酸酶信号通路的影响。方法采用腹主动脉缩窄制备SD大鼠左室肥厚模型。实验分为假手术组,模型组,吴茱萸总碱低(10 mg/kg),中(20 mg/kg)、高剂量组(40 mg/kg)和L-arg(200 mg/kg)阳性药对照组。模型制备次日大鼠灌胃给药4周,记录大鼠体重(BW),测量左室重量(LVW),计算左室肥厚指数(LWHI),行病理切片观察心肌肥厚,以明确吴茱萸总碱防治左室肥厚效应。检测左室血流动力学参数,实时荧光定量PCR检测心肌ANF、CaN mRNA的表达。结果与假手术组比较,模型组大鼠明显增加LVW和LWHI(P<0.05),病理学见左室心肌结构和心肌细胞严重受损,左室内压峰值(LVSP)和舒张期末压(LVEDP)明显升高(P<0.05),而±dp/dt max显著降低(P<0.01)。与模型组比较,吴茱萸总碱中、高剂量明显抑制大鼠因腹主动脉缩窄所致LVW、LWHI增加,LVSP、LVEDP的升高和±dp/dt max降低,明显减轻心肌病理损伤,下调ANF mRNA和CaN mRNA的表达(P<0.01)。结论吴茱萸总碱20 mg/kg和40 mg/kg可防治腹主动脉缩窄所致大鼠心肌肥大,其机制可能与抑制钙调磷酸神经酶信号通路有关。Objective To investigate the inhibition of Evodia total alkaloids （ETA） on rat left ventricular hypertrophy （LVH） induced by eoaretation of abdominal aorta （COA） and the effects of ETA on ealeineurin （CaN） signaling pathway. Methods Rat left ventrieular hypertrophy model was established by COA. All the animals were randomly divided into sham- operated group, COA model group, L- arginine （L- arg） （200 mg/kg/d） group, ETA （ 10 mg/kg/d, 20 mg/kg/d and 40 mg/kg/d） groups. Rats were given ETA intragastrically and L - arg with intraperitoneal injection from the day after COA operation for 4 w. The body weight （BW） and left ventrieular weight （LVW） were recorded to calculate the left ventrieular hypertrophy index （LVHI）. The Patho- logical sections were performed to observe the myocardial hypertrophy. Rat hemodynamics parameters were meas- ured by BL -420 physiological recorder system. The mRNA expressions of CaN and ANF were detected by real time reverse transcription - polymerase chain reaction （ RT - PCR）. Results Compared with the sham - operated group, the LVW and LWHI in COA model group were increased significantly （P 〈 0.05 ） and the left ventrieular structure and cardiac cells were significantly damaged with the elevated LVSP and LVEDP and the decreased ±dp/dt max Compared with the model group, ETA （20 mg/kg and 40mg/kg） decreased LVW, LWHI, LVSP andLVEDP and increased ±dp/dt max and ameliorated myocardial pathology damage and suppressed the CaN and ANF mRNA expressions. Conclusion ETA could suppress the left ventricular hypertrophy induced by COA, the mechanisms might be related to the inhibitory effects on CaN signaling pathway.

关 键 词：吴茱萸总碱 腹主动脉缩窄 左心室肥大 钙调神经磷酸酶 

分 类 号：R284.2[医药卫生—中药学]