中国临床药理学与治疗学2017，Vol.22Issue(12)：1326-1331,6.
二甲双胍通过上调谷胱甘肽-S-转移酶μ2抑制大鼠心肌肥厚
Metformin inhibits myocardial hypertrophy by up-regulating glutathione-S-transferase μ2
摘要
Abstract
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 p47phox and Nox4 in left ventricle were investigated by Western blot.The O2·-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/dt max) decreased significantly in SHR;the protein expression and enzyme activity of left ventricular GSTM2 were significantly decreased;the expression of p47phox,Nox4 and the generation of O2·-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/dt max) increased in SHR administration group;the protein expression and enzyme activity of left ventricular GSTM2 were significantly increased in SHR administration group.the expression of p47phox,Nox4 and the generation of O2·-was significantly decreased in the left ventricles of SHR administration group;the value of P was less than 0.01 and the difference was statistically significant.CONCLUSION:Metformin can significantly reverse the myocardial hypertrophy in SHR,which might be associated with the up-regulation of GSTM2 expression,decrease the expression of p47phox,Nox4 and O2·-generation,elimination of oxidative stress.关键词
二甲双胍/心肌肥厚/自发性高血压大鼠/谷胱甘肽-S-转移酶μ2/氧化应激Key words
metformin/myocardial hypertrophy/spontaneously hypertensive rat/glutathione-stransferaseμ2/oxidative stress分类
医药卫生引用本文复制引用
李忠洪,王平,周四桂,王桂香..二甲双胍通过上调谷胱甘肽-S-转移酶μ2抑制大鼠心肌肥厚[J].中国临床药理学与治疗学,2017,22(12):1326-1331,6.基金项目
国家自然科学基金资助项目(81000072 （）
81670239) （）
广东省科技计划项目(2014A020212315) （2014A020212315）
广东省自然科学基金项目(2016A030313729) （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 （）
