血管紧张素酶抑制剂对自发性高血压大鼠颈动脉血管平滑肌抑癌基因和原癌基因表达的干预作用

The Effect of ACEI on Expresson of Tumor Suppressor Gene and Oncogenes in Carotid Smooth Muscle from the Spontaneous Hyperten- sion Rats

目的探讨自发性高血压大鼠颈动脉中抑癌基因P53和原癌基因c-jun、c-fos、c-mycmRNA表达及其血管紧张素酶抑制剂的影响。方法自发性高血压大鼠实验前检测mRNA的表达情况,实验组随机分为蒙诺组(M组)、科素雅组(K组)、硝苯地平组(Ca+组)。分别加用蒙诺(2mg·kg-1·d-1)、科素亚(10mg·kg-1·d-1)、硝苯地平(2mg·kg-1·d-1)饲养12周。用逆转录聚合酶链式反应检测两种基因的表达水平。正常雄性大鼠作为对照。结果SHR颈动脉中,两类基因均有明显的高表达,较WKY有显著差异(P<0.05)。治疗12周后,两类基因在M组中表达明显减弱,较K组、Ca+组有显著差异(P<0.05)。结论自发性高血压大鼠颈动脉组织中抑癌基因P53和原癌基因c-jun、c-fos、c-myc均有高表达,血管紧张素酶抑制剂蒙诺能明显地抑制其表达;这两类基因的活化可能与自发性高血压大鼠颈动脉血管重构有关,血管紧张素酶抑制剂可能通过对P53和c-jun、c-fos、c-myc等基因表达的抑制作用逆转血管重构。

Objective TO study the effect of angiotensin enzyme inhibitor(ACEI)on the mRNA expression of tumor suppressor gene P53 and oncogene c-jun,c-fos,c-myc in carotid smooth muscle from the spontaneous hypertension rat (SHR).Methods check the mRNA expression before treatment,then SHR divide randomly into M (Monopril),K(Cozaar) and Ca + (Nifedipine)groups.SHR was treated with Monopril(2mg·kg -1 ·d -1 ),Cozaar(10mg· kg -1 ·d -1 ) and Nifedipine (2mg·kg -1 ·d -1 )for 12 weeks. The mRNA expression of these genes were examined by RT-PCR.As control group,WKY was experimented too. Result the mRNA of these genes expressed obviously in SHR, and had evidently difference comparing to WKY(P<0.05);After 12 weeks treatment,the mRNA expression of these genes had been weakened obviously, and had evidently difference comparing to K and Ca + groups’(P<0.05). Conclusion In SHR carotid smooth muscle,the expression of tumor suppressor gene P53 and oncogene c-jun, c-fos and c-myc expressed obviously,and angiotensin enzyme inhibitor(ACEI) Monopril can weaken their expression; The expression probably relate to carotid reconstruction; Angiotensin enzyme inhibitor probably reverse the reconstruction by inhibiting the expression of the two kind genes.