PI3K/Akt通路介导TRPV1抑制离体小鼠心脏缺血再灌注后的细胞凋亡  

TRPV1 inhibits apoptosis mediated by PI3K/Akt signaling pathway in myocardial ischemia/reperfusion mouse heart

作　　者：姜小雪[1] 刘关羽[2] 雷寒[1] 张羿[1] 冯清平[3] 黄玮[1] 

机构地区：[1]重庆医科大学附属第一医院心血管内科,重庆400016 [2]重庆医科大学附属第一医院泌尿外科,重庆400016 [3]加拿大西安大略大学医学院生理和药理学系

出　　处：《基础医学与临床》2016年第9期1187-1192,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81170188;30971212);重庆市自然科学基金(CSCT2009BB5069);国家临床重点专科建设项目(2011-170)

摘　　要：目的研究瞬时受体电位香草酸亚型1(TRPV1)对离体小鼠心脏缺血/再灌注(I/R)后心肌细胞凋亡的影响及与PI3K/Akt通路的关系。方法 TRPV1基因敲除(TRPV1^(-/-))和野生型(WT)小鼠各54只,均各随机分为假手术组(sham)、缺血再灌注组(I/R)和LY294002处理组(LY)。建立Langendorff离体心脏灌注模型,检测心功能;灌注结束后,TTC染色法检测心肌梗死面积;TUNEL法检测心肌细胞凋亡;Western blot检测Bcl-2、Bax、Akt和p-Akt的蛋白表达水平。结果 I/R后,TRPV1^(-/-)小鼠较WT小鼠的LVDP明显降低(P<0.001),LVEDP明显升高(P<0.001),同时心肌梗死面积和心肌凋亡细胞明显增加(P<0.01),Bcl-2/Bax和p-Akt表达水平下降(P<0.001)。LY294002阻断PI3K后,与相应的I/R组相比,WT小鼠心肌梗死面积明显扩大(P<0.001),心肌凋亡细胞明显增加(P<0.01),Bcl-2/Bax和p-Akt蛋白表达水平降低(P<0.001)。结论 TRPV1可能通过PI3K/Akt通路抑制离体小鼠心脏缺血/再灌注所致的心肌细胞凋亡。Objective To investigate the effects of TRPV1 on myocardial apoptosis and PI3K/Akt expression during ischemia/reperfusion injury in mice. Methods Totally 54 wild type （WT） mice and 54 TRPVl-null mutant （ TRPV1^-/- ） mice were randomly divided into six groups ： WT ＋ sham group, TRPV1^-/- ＋ sham group, WT ＋ I/ R group, TRPV1^-/- ＋ I/R group, WT ＋ LY group and TRPV1^-/- ＋ LY group. The mice hearts were perfused with a Langendorff apparatus and the indexes of cardiac mechanical function were measured. Cardiomyocyte apopto- sis was detected by TUNEL. Expression of Bcl-2, Bax, Akt and p-Akt was measured by Western blot. Infarct size was measured by TFC staining. Results Compared with the WT ＋ I/R group, the LVEDP significantly increased, and LVDP significantly decreased in the TRPV1^-/- ＋ I/R group （P 〈 0. 001 ）. The expression of Bcl-2/Bax and p-Akt in the myocardium of the TRPV1^-/- ＋ I/R group was significantly lower than that of the WT ＋ I/R group （P 〈0. 001）, PV1^-/- ＋ I/R the PI3K with minished exp I/R-induced Key words ： while the proportion of apoptotic cardiomyocytes and infarct size significantly increased in the TR- group as compared with the WT ＋ I/R group （P 〈 0. 01 ）. Compared with I/R group, blockade of LY294002 significantly increased the apoptosis index （P 〈 0. 01 ）, infarct size （P 〈0. 001 ） and di- ssion of Bcl-2/Bax and p-Akt in WT ＋ LY group （P 〈 0. 001 ）. Conclusions TRPV1 may attenuate apoptosis in isolated heart through PI3K/Akt signaling pathway .

关 键 词：心肌缺血/再灌注损伤 瞬时受体电位香草酸通道 PI3K/AKT 凋亡 

分 类 号：R541[医药卫生—心血管疾病]