Effects of nicorandil, glutamine, metoprolol used in single and combination on antiapoptosis ability of cardiocytes and expression of HSP70 against myocardial ischemia/reperfusion injury in rats / 中国药理学通报

ABSTRACT

Aim To investigate the protective effects of nicorandil, glutamine and metoprolol used in single and combination on the antiapoptosis ability of cardio-cytes and the expression of HSP70 after myocardial is-chemia/reperfusion injury in rats. Methods Male Wistar rats were divided randomly into seven groups( 1 ) Sham groupin which the coronary artery was not roped;(2) I/R groupin which only 30 min ischemia and 120 min reperfusion of LAD was executed; ( 3 ) Nicorandil group; ( 4 ) Glutamine group; ( 5 ) Meto-prolol group; ( 6 ) Nic + Glu + Met ( NGM ) group;(7) low dose of Nic+Glu+Met ( NGML) group. In the pharmacological precondition groups, correspond-ing drugs were administered 30 min before I/R proto-col, and the initial drug dose in each group was 1 mg ·kg-1 . Myocardial apoptotic rates were measured with TUNEL ( terminal dexynucleotidyl transferase-mediated dUTP nick end labeling) , and the expression of apop-tosis related proteins-Bcl-2/Bax and protective pro-tein-HSP70 was detected by Western blot. ResultsIn I/R group, the apoptotic rate in ischemic region was very high ( 36.9% ± 10.3%) , and Bcl-2/Bax was very low ( 0.14 ±0.08 ) . Compared with I/R group, the apoptotic rate of pharmacological precondition groups was decreased significantly ( P <0.01 ) , and the ratio of Bcl-2 to Bax was raised ( P<0.01 ) . Com-pared with Sham group, the expression of HSP70 in-creased significantly ( P<0.01 ) in I/R group. Com-pared with IR group, the expression of HSP70 of phar-macological precondition groups was elevated ( P <0.01 ) , and the expression in NGM group was higher than in the single drug group ( P<0.01 ) . Conclusion Compared with single therapy after I/R in rat, the combination therapy of nicorandil, glutamine, meto-prolol can decrease the apoptotic rate, and the expres-sion of apoptosis related proteins is developed. In the mean time, the expression of protective protein HSP70 is elevated.