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目的:评价金属硫蛋白(metallothionein, Met)在体内是否能改善硝酸甘油耐药的发生。方法:大鼠给予硝酸甘油(nitroglycerin, Nit)贴剂治疗两天(0.05 mg·h~(-1))以产生耐药。于耐药大鼠预先给予ZnCl_2以诱导内源性Met的合成及给予外源性Met15 mg·kg~(-1)·d~(-1)连续2 d。结果:Nit+ZnCl_2组大鼠肝脏、血浆Met明显高于对照组(C组)。Nit组大鼠离体主动脉环的舒张反应最低。Nit+ZnCl_2组大鼠及Nit+Met组大鼠对SNP的降压反应明显强于Nit组。结论:外源性Met或内源性诱导合成的Met可以改善大鼠Nit耐药的发生。
OBJECTIVE: To evaluate whether metallothionein (Met) can ameliorate the development of nitroglycerin resistance in vivo. Methods: Rats were given nitroglycerin (Nit) patch for two days (0.05 mg · h -1) to produce drug resistance. The drug-resistant rats were pre-given with ZnCl 2 to induce the synthesis of endogenous Met and the exogenous Met15 mg · kg -1 d -1 for 2 d. Results: The liver and plasma Met levels in Nit + ZnCl 2 group were significantly higher than those in control group (C group). Nitric oxide in isolated rat aortic rings was the lowest. The hypotensive response to SNP in Nit + ZnCl 2 and Nit + Met groups was significantly greater than that in Nit group. Conclusion: Exogenous Met or endogenously induced Met can improve the occurrence of Nitrate resistance in rats.