摘要
目的:探讨二甲双胍对自发性高血压大鼠(spontaneously hypertensive rats,SHR)左心室谷胱甘肽-S-转移酶μ_2(glutathione-s-transferaseμ_2,GSTM2)的作用,以及二甲双胍对心肌肥厚防治的机制。方法:以16周龄的Wistar-Kyoto(WKY)和自发性高血压大鼠(SHR)作为实验对照,以8周龄的WKY和SHR持续给药二甲双胍(Met)8周作为实验组。采用NIBP大鼠血压心率测定仪定期检测大鼠收缩压,利用BL-420生物实验系统、4导生理记录仪检测大鼠血流动力学参数,称量大鼠左心室及体质量并计算左室重量指数,采用酶联免疫吸附试验(ELISA)检测左心室GSTM2酶活性,利用Western blot检测左心室GSTM2、p47phox及Nox4的蛋白表达,二氢乙啶(dihydroethidium,DHE)染色检测O_2·^-的含量。结果:与对照组相比,SHR组大鼠血压、左室重量指数及左室舒张末压(left ventricular end-diastolic pressure,LVEDP)明显增加;室内压最大上升和下降速率(maximal rate of increase and decrease of left-ventricle pressure development,±dp/dtmax)明显下降;左心室GSTM2的蛋白表达及酶活性明显下降;左心室P47phox及Nox4的蛋白表达明显增高;O_2·^-的产生明显增多;差异具有统计学意义(P<0.01)。与SHR组相比,SHR二甲双胍治疗8周后,左室重量指数及LVEDP明显下降;±dp/dtmax明显升高;左心室GSTM2的蛋白表达及酶活性明显升高;左心室P47phox及Nox4的蛋白表达明显下调;O_2·^-的产生明显减少;差异有统计学意义(P<0.01)。结论:二甲双胍可以逆转SHR心肌肥厚,可能与增加左心室GSTM2的蛋白表达、降低p47phox及Nox4的蛋白表达、减少活性氧产生、消除氧化应激密切相关。
AIM： To observe the effect of metformin on the expression of GSTM2 in spontaneously hypertensive rats,and to investigate the mechanism of the reversal of myocardial hypertrophy by metformin.METHODS： Sixteen weeks old WistarKyoto（ WKY） and spontaneously hypertensive rats（ SHR） were used as the experimental control.Eight weeks old WKY and SHR were administered to metformin（ Met） continuously for 8 weeks as the experimental group.Systolic pressure of rats was regularly determined by NIBP instrument of heart rate and blood pressure.The hemodynamic parameters were tested by BL-420 biological experimental system and 4 track physiological recorders.The weights of left ventricle and rats were collected to calculate the left ventricular mass index.The activity of GSTM2 enzyme in left ventricle was detected by Enzyme-linked immunosorbent assay（ ELISA）.The protein expression of GSTM2 and p47 phox and Nox4 in left ventricle were investigated by Western blot.The O_2·^- levels were measured by staining with dihydroethidium（ DHE）.RESULTS： Compared with the experimental control,the blood pressure and left ventricular mass index and left ventricular end-diastolic pressure（ LVEDP） increased in SHR; the maximal rate of increase and decrease of left-ventricle pressure development（ ± dp/dtmax） decreased significantly in SHR; the protein expression and enzyme activity of left ventricular GSTM2 were significantly decreased;the expression of p47 phox,Nox4 and the generation of O_2·^- were significantly increased in the left ventricles of SHR; the value of P was less than 0.01 and the difference was statistically significant.Compared with the SHR group,the SHR were administered with metformin（ Met） continuously for 8 weeks.The left ventricular mass index and left ventricular end-diastolic pressure（ LVEDP） decreased observably in SHR administration group; the maximal rate of increase and decrease of left-ventricle pressure development（ ± dp/dtmax） increased in SHR administration group; the
出处
《中国临床药理学与治疗学》
CAS
CSCD
2017年第12期1326-1331,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金资助项目(81000072
81670239)
广东省科技计划项目(2014A020212315)
广东省自然科学基金项目(2016A030313729)
广东省"十二五"医学重点学科
依托广东药科大学附属第一医院
药学院
