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川穹嗪对大鼠心肌肥大JAK STAT通路作用

【摘要】  目的 了解川穹嗪对大鼠心肌肥大JAKSTAT通路的影响。方法 建立心肌肥大动物模型,40只大鼠随机分为4组,每组10只,分别为血管紧张素Ⅱ(AngⅡ)组(给予AngⅡ 36 mg·kg-1·d-1)、AngⅡ加川穹嗪组(给予AngⅡ 36 mg·kg-1·d-1,川穹嗪50 mg·kg-1·d-1)、AngⅡ加PBS组(给予AngⅡ 36 mg·kg-1·d-1,PBS 50 mg·kg-1·d-1)、对照组(给予生理盐水36 mg·kg-1·d-1),计算心肌肥大指数。培养、鉴定新生大鼠心肌细胞,每天分别给予AngⅡ 1×10-7 mol/L(AngⅡ2组)、AngⅡ 1×10-7 mol/L+川穹嗪1×10-4 mol/L(AngⅡ加川穹嗪2组),以不加药物作为对照2组,培养7 d,应用RTPCR方法检测各组大鼠心肌细胞心房利钠肽(ANP)相对水平,Westernblot检测心肌肥大信号转导途径分子pJAK2、pJAK1、pSTAT3表达。结果 AngⅡ组与对照组比较,心肌肥大指数明显增高,差异有统计学意义(F=32.675,q=6.25,P<0.01),AngⅡ+川穹嗪组与AngⅡ组相比较,心肌肥大指数明显下降,差异有显著意义(q=5.19,P<0.05)。AngⅡ2组与对照2组比较,ANP mRNA表达增加,差异有显著性(F=45.674,q=11.23,P<0.01);AngⅡ+川穹嗪2组与AngⅡ2组比较,ANP mRNA表达减少,差异有显著性(q=7.53,P<0.01)。AngⅡ2组加入川穹嗪前后pJAK1、pJAK2、pSTAT蛋白表达量比较,差异有显著性(F=24.456~36.549,q=8.02~10.25,P<0.05、0.01)。 结论 川穹嗪能通过干扰心肌肥大JAKSTAT信号转导通路抑制心肌肥大。

【关键词】  肌细胞,心脏;肥大;血管紧张素Ⅱ;信号传导;川穹嗪

EFFECTS OF TETRAMETHYLPYRAZINE ON JAKSTAT SIGNAL TRANSDUCTION IN CARDIOMYOCYTE HYPERTROPHYZHANG LI, GAO MEIHUA (Department of Immunology, Qingdao University Medical College, Qingdao 266021, China); [ABSTRACT] Objective To study the effect of Tetramethylpyrazine (TMZ) on JAKSTAT signal transduction in rats with cardiomyocyte hypertrophy. Methods A cardiomyocyte hypertrophy (CH) model was made in 40 Wistar rats, which wereequally randomized to four groups. The first group was given Ang Ⅱ 36 mg·kg-1·d-1; the second, Ang Ⅱ 36 mg·kg-1·d-1 and TMZ 50 mg·kg-1·d-1; the third, Ang Ⅱ 36 mg·kg-1·d-1 and PBS 50 mg·kg-1·d-1; and the control, saline 36 mg·kg-1·d-1. Myocardial hypertrophy index (MHI) was calculated. Newborn cardiocytes in rats were caltured for seven days and identified. The first group was given Ang Ⅱ 1×10-7 mol/L; the second, Ang Ⅱ 1×10-7 mol/L and TMZ 1×10-4 mol/L; and the control, no medicine given. The relative level of of atrial natriuretic peptide was detec

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