通脉汤方对实验性动脉粥样硬化家兔胸主动脉表皮生长因子受体和c-myc基因表达的影响

Effect of Tongmai Recipe on Epidermal Growth Factor Receptor and Protooncogene c-myc mRNA Expression in Aorta of Atherosclerotic Rabbit

目的探讨通脉方对实验性动脉粥样硬化家兔胸主动脉表皮生长因子受体和c-myc基因表达的影响。方法日本大耳白兔40只,随机分为4组:①对照组10只,以普通饲料喂养,每日两次;②模型组10只,以高胆固醇饲料[胆固醇0.5g/(kg.d)、蛋黄2g/(kg.d)和猪油2g/(kg.d)]喂养,每日两次;③通脉汤方低剂量组(简称低剂量组)10只,高胆固醇饲料喂养(剂量同模型组),同时予通脉汤方灌胃,每只剂量相当于生药7.3g/(kg.d),分上下午两次给药;④通脉汤方高剂量组(简称高剂量组)10只,高胆固醇饲料喂养(剂量同模型组),同时予通脉汤方灌胃,每只剂量相当于生药21.9g/(kg.d),分上下午两次给药;共喂养16周。运用免疫组织化学染色法检测主动脉表皮生长因子受体的表达,同时用内参比逆转录聚合酶链反应定量分析c-mycmRNA在主动脉的表达。结果模型组主动脉表皮生长因子受体及c-mycmRNA表达显著高于对照组(分别为0.327±0.030比0.209±0.006,P<0.01;0.52±0.11比0.34±0.07,P<0.01);高剂量组主动脉表皮生长因子受体及c-mycmRNA表达显著低于模型组(分别为0.242±0.014比0.327±0.030,P<0.01;0.41±0.07比0.52±0.11,P<0.05);低剂量组与模型组比较无显著差异(分别为0.301±0.027比0.327±0.030P>0.05;0.44±0.09比0.52±0.11P>0.05)。结论①动脉粥样硬化时促进血管平滑肌细胞增殖的表皮生长因子受体及原癌基因c-mycmRNA表达增强。②通脉汤方通过抑制血管壁表皮生长因子受体及c-myc基因的表达,从而抑制血管平滑肌细胞增殖。

Aim Aim To study effect of Tongmai recipe on epidermal growth factor receptor and protooncogene c-myc mRNA expression in aorta of atherosclerotic rabbit.Methods Forty rabbits were randomly divided into four groups：①Control group：10 rabbits were fed with common food twice daily;②Model group：10 rabbits were fed with high cholesterol diet supplemented by cholesterol 0.5 g/（kg·d）,yolk 2 g/（kg·d） and lard 2 g/（kg·d）;③Low dosage Tongmai recipe administration group（LT group）：10 rabbits were fed with high cholesterol diet as well as in model group,simultaneously administrated with Tongmai recipe at a dosage of 7.3 g/（kg·d）,④High dosage Tongmai recipe administration group（HT group）：10 rabbits were fed with high cholesterol diet as well as in model group,simultaneously administrated with Tongmai recipe at a dosage of 21.9 g/（kg·d）.After 16 weeks,epidermal growth factor receptor were assessed by immunohistochemistric assays.c-myc mRNA in aorta were quantified with semiquantitative RT-PCR methodology.Results we found that in model group,accumulation of epidermal growth factor receptors and mRNA expression of protooncogene c-myc in aorta significantly increased as compared to those in control group（0.327±0.030 vs 0.209±0.006,P〈0.01;0.52±0.11 vs 0.34±0.07,P〈0.01）.In HT group,they significantly decreased as compared to those in model group（0.242±0.014 vs 0.327±0.030,P〈0.01;0.41±0.07 vs 0.52±0.11,P〈0.05）.In LT group,there was no significant change as compared to those in model group（0.301±0.027 vs 0.327±0.030 P〉0.05;0.44±0.09 vs 0.52±0.11 P〉0.05）.Conclusion ①Expression of epidermal growth factor receptor and c-myc which promoted proliferation of vascular smooth muscle cells increased in atherosclerotic individuals.②Tongmai recipe may possesses the role of depression of proliferation of vascular smooth muscle cells by depressing the expression of epidermal growth factor receptor and protooncogene c-myc.