5-羟色胺受体拮抗剂在预防压力过超载诱导的小鼠心肌肥大中的作用

Role of 5-hydroxytryptamine3 receptor antagonists in protecting pressure overload-induced cardiac hypertrophy in rats

目的:探讨5-羟色胺3(5-hydroxytryptamine3,5-HT3)受体拮抗剂在预防压力过超载诱导的小鼠心肌肥大中的作用。方法:将32只昆明小鼠随机分为假手术组(n=8)、主动脉缩窄术(transverse aortic constriction,TAC)模型组(n=8)、TAC+昂丹司琼(ondansetron,Ond)组(n=8)及TAC+托烷司琼(tropisetron,Tro)组(n=8)4组;给予TAC手术,并在术后3 d分别给予Ond及Tro进行干预,4周后处死,测量各组小鼠的体质量、心脏质量、左心质量及心脏/体质量比值及左心室/体质量比值,并检测血浆去甲肾上腺素(norepinephrine,NE)水平及进行心脏病理切片Masson’s染色。18只小鼠随机分为对照组(n=6),Tro组(n=6),Ond组(n=6),不进行TAC手术,观察血浆NE浓度变化。结果:5-HT3受体拮抗剂Ond、Tro能够对压力负荷诱导的心肌肥大有着很好的保护作用。同时能降低血浆中NE水平(F=7.96,P=0.001)。结论:5-HT3受体拮抗剂能够对压力负荷诱导的心肌肥大有着很好的保护作用,机制之一可能是通过遏制交感神经的过度兴奋。

Objective：To discuss the role of 5-hydroxytryptamine3 （5-HT3） receptor antagonist in the prevention of pressure overload induced myocardial hypertrophy. Methods：Thirty-two Kunming mice were randomly divided into four groups：sham-operation group （n=8）,transverse aortic constriction（TAC） group（n=8）,TAC ＋ ondansetron（Ond） group（n=8） and TAC ＋ tropisetron（Tro） group （n=8）. TAC operation was performed and Ond and Tro intervene was followed on 3 d postoperatively. Rats were killed 4 weeks later and their body weight, heart weight,left heart weight, heart/weight ratio and left ventricular/weight ratio were measured and counted. Plasma norepinephrine （NE） levels were detected and heart pathological Masson staining was conducted. Eighteen Kunming mice were randomly divided into control group（n=6）,Tro group（n=6） and Ond group（n=6）. TAC operation was not performed and changes in plasma NE levels were observed. Results：Ond and Tro reduced the elevated plasma NE levels in mice with cardiac hypertrophy （F=7.96,P=0.001）. Ond and Tro exerted postive effect on pressure ouerload induced myocardial hypertrophy. Conclusions：5-HT3 receptor antagonists can protect cardiac hypertrophy and restore desensitization of cardiac adrenergic responsiveness, the mechanism of which may be through reducing the sympathetic activity.