S-甲基异硫脲对阿霉素致大鼠心肌线粒体腺苷三磷酸合酶活性改变的影响

Effect of S-methylisothiourea on induced activity changes of adenosine triphosphate synthase by adriamycin in myocardial mitochondria of rats

目的研究S-甲基异硫脲(SMT)对阿霉素(ADR)所致大鼠心肌线粒体腺苷三磷酸合酶(ATPS)活性改变的影响。方法大鼠腹腔注射ADR(5.0 mg.kg-1)1次,给ADR处理的大鼠静脉注射不同剂量的SMT1次进行干预。分别用寡霉素—无机磷法、血红蛋白氧化法测定心肌线粒体的ATPS活性、一氧化氮合酶活性;分别用荧光素酶法、硝酸还原酶法测定心肌线粒体的腺苷三磷酸(ATP)含量、一氧化氮(NO)含量;用逆转录-聚合酶链反应方法检测心肌线粒体的ATPS6 mRNA、ATPS8 mRNA表达。结果SMT(5.0,10.0,20.0 mg.kg-1)拮抗ADR所致心肌线粒体的ATPS活性降低、诱导型一氧化氮合酶(iNOS)活性增加(P<0.01);拮抗ADR所致心肌线粒体的ATP含量降低、NO含量增加(P<0.01);拮抗ADR所致心肌线粒体的ATPS6 mRNA、ATPS8 mRNA表达水平降低(P<0.01)。结论SMT拮抗ADR导致心肌线粒体的ATPS6 mRNA、ATPS8 mRNA表达水平降低而拮抗ADR导致ATPS活性降低,从而改善心肌线粒体供能;SMT拮抗ADR导致心肌线粒体的ATPS6 mRNA、ATPS8 mRNA表达水平降低可能与其选择性地抑制ADR所诱导心肌线粒体的iNOS活性使NO产生减少,从而减少NO抑制心肌线粒体的ATPS6 mRNA、ATPS8 mRNA表达有关。

Aim To study the effect of S-methylisothio- urea （SMT） on induced activity changes by adriamycin （ADR） of the adenosine triphosphate synthase （ATPS） in myocardial mitochondria of rats. Methods Rats were treated with ADR by intraperioneal injection （5.0 mg · kg-l, only one time）, and then rats treated by ADR were intervened by SMT at different dosages by intravenous injection （only one time）. Oligomyein-in- organic phosphorous ion method, hemoglobin-oxidation method, luciferase method and nitrate reductase meth- od were used to determine the activities of ATPS and nitric oxide synthase, the contents of ATP and nitric oxide （NO） in myocardial mitochondria, respectively. The expression of ATPS6 mRNA and ATPS8 mRNA were detected by reverse transcription-polymerase chain reaction method in myocardial mitochondria. Results SMT（5.0,10. 0,20. 0 mg~ kg-1 ） had antagonistic effect on reducing the activity of ATPS induced by ADR, increasing the activity of inducible nitric oxide synthase （iNOS）, reducing the content of ATP induced by ADR, increasing the content of NO （P 〈 0. 01 ）, and reducing the expressive levels of ATPS6 mRNA and ATPS8 mRNA in myocardial mitochondria induced by ADR（P 〈 0.01 ）. Conclusions SMT an- tagonizes the reduced expression of ATPS6 mRNA and ATPS8 mRNA, and antagonized the reduced activity of ATPS in myocardial mitochondria induced by ADR, thereby improves supply of myocardial mitochondrial energy. SMT antagonizes the reduced expression of ATPS6 mRNA and ATPS8 mRNA in myocardial mito- chondria induced by ADR, which may be related to its selectively inhibiting the iNOS activity in myocardial mitochondria induced by ADR, thus reducing the in- hibitory effects of NO on the expression of ATPS6 mR- NA and ATPS8 mRNA in myocardial mitochondria.