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

摘要:

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。

Abstract:

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.