活血潜阳方对自发性高血压大鼠心肌肥厚组织原癌基因c-fos和c-myc表达的影响

Effects of Huoxue Qianyang Formula on expressions of proto-oncogenes c-fos and c-myc in spontaneous hypertensive rats with ventricular hypertrophy

目的:通过分析左心室心肌原癌基因c-fos和c-myc mRNA及蛋白的表达,探讨活血潜阳方改善自发性高血压大鼠(spontaneous hypertensive rat,SHR)左心室肥厚的作用机制。方法:以10周龄的SHR为高血压左心室肥厚模型,随机分为SHR模型组,中药大、中、小剂量治疗组,西拉普利治疗组,年龄和性别相匹配的京都(Wistar-Kyoto,WKY)大鼠作为正常对照组,每组5只。灌胃14周后,取大鼠心脏组织,用原位杂交组织化学法和免疫组化法分别检测心肌c-fos和c-myc mRNA及蛋白的表达。结果:24周龄模型组SHR左心室肥厚心肌的原癌基因c-fos和c-myc mRNA及蛋白的表达与WKY大鼠比较明显增强(P<0.01)。与SHR模型组比较,大、中和小剂量活血潜阳方组大鼠左心室心肌组织中c-fos和c-myc mRNA的表达下降(P<0.05);大、中剂量活血潜阳方可降低c-myc蛋白的表达,但对c-fos蛋白表达的影响与模型组比较,差异未见统计学意义。结论:活血潜阳方可以下调SHR心肌组织中原癌基因c-myc的表达,可能是改善高血压左心室肥厚的重要机制之一,是否通过对c-fos表达的影响治疗左心室肥厚尚不能确定。

Objective： To explore the possible mechanism of Huoxue Qianyang Formula （HXQYF）, a compound traditional Chinese herbal medicine, in reversing the left ventricular hypertrophy （LVH） of spontaneous hypertensive rats （SHRs） by analyzing the expressions of mRNAs and proteins of proto-oncogenes c-los and c-myc in left ventricular muscle. Methods： The experimental study was carried out rats were served as normal control （n=5, norma divided into five groups： untreated group n=5, n SHRs, the sex- and age-matched Wistar-Kyoto （WKY） saline 10 ml/kg daily）. Twenty-five SHRs were randomly normal saline 10 ml/kg daily）, high-dose HXQYF-treatedgroup （n=5, 0.84 g/ml HXQYF, 10 ml/kg dally）, medium-dose HXQYF-treated group （n=5, 0.42 g/ml HXQYF, 10 ml/kg daily）, low-dose HXQYF-treated group （n=5, 0.21 g/ml HXQYF, 10 ml/kg daily） and cilazapril-treated group （n = 5, 1 mg/ml cilazapril, 10 ml/kg daily）. The drugs were intragastrically administered once daily for 14 weeks. The expressions of c-myc in left ventricular muscle were detected separately immunohistochemical method. mRNAs and proteins of proto-oncogenes c-fos and by in situ hybridization histochemical method and immunohistochemical method. Results： Compared with the normal control group, the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were significantly increased in untreated group （P〈0.01）. After treatment, the expressions of c-los and c-myc mRNAs in left ventricular muscle in HXQYF-treated groups were significantly down-regulated as compared with those of the untreated group （P〈0.05）. The expressions of c-myc protein were also significantly decreased in high- and medium-dose HXQYF-treated groups as compared with the untreated group （P〈0.05）, but it had no significant effects in protein expression of c-fos in the three HXQYF-treated groups. Conclusion. HXQYF can inhibit the expression of c-myc in ventricular hypertrophy tissue, which may be the mechanism in treating LVH of hypertention.