同型半胱氨酸对球囊损伤大鼠颈动脉原癌基因表达及新生内膜增生的影响

Effect of homocysteine on the expression of protooncogene and neointimal hyperplasia in rat carotid arteries after balloon injury

目的 观察高蛋氨酸饮食诱导的高同型半胱氨酸 (Hcy)血症对大鼠颈动脉球囊损伤后血管组织原癌基因c fos及c junmRNA表达及新生内膜增生的影响 ,探讨Hcy在血管球囊损伤后新生内膜过度增生中的作用及可能机制。 方法 采用RT$CPCR方法检测血管组织c fos及c junmRNA表达情况 ,并做半定量分析。采用光镜和计算机图像分析定量方法观察高Hcy血症对大鼠颈动脉内皮损伤后新生内膜增生的影响。 结果 低蛋氨酸组和高蛋氨酸组c fos及c junmRNA的表达〔分别为 (1 4 0± 0 2 1)、(1 4 3± 0 2 5 )及 (1 6 8± 0 2 7)、(1 71± 0 30 )〕均高于对照组〔分别为 (1 10± 0 15 )、(1 0 0± 0 13) ,P <0 0 5和 0 0 1)〕 ,高蛋氨酸组也明显高于低蛋氨酸组 (P <0 0 5 )。与对照组比较 ,低蛋氨酸组、高蛋氨酸组的新生内膜增生明显 ,计算机图像定量分析表明血管损伤后 14d ,低和高蛋氨酸组新生内膜增生面积和内.M中膜面积比率比对照组分别增加 87%、98%和 97%、10 9%(均为P <0 0 1) ,管腔面积在低、高蛋氨酸组比对照组分别减少 4 5 %、5 5 % (P <0 0 5 )。 结论 (1)高Hcy血症能使球囊损伤后颈动脉新生内膜增生恶化 ,预示高Hcy血症可能是血管内皮球囊损伤后再狭窄的一个独立危险因素 ;(2 )Hcy能上调血管内皮损?

Objective To study the effect of homocysteine(Hcy) on the expression of c-fos and c-jun mRNA and neointimal hyperplasia in rat common carotid artery, and to explore the possible mechanism of homocysteine exacerbating neointima formation after balloon injury. Methods The mRNA expression of c-fos and c-jun were detected by semi-quantitative RT-PCR in the common carotid artery. The morphology of arterial intima and media was studied by optical microscopy and image analysing system. Results The mRNA expression of c-fos and c-jun was significantly elevated in the low methionine(LM)〔(1.40±0.21),(1.43±0.25)〕 and high methionine(HM) 〔(1.68±0.27),(1.71±0.30)〕 than that in the control group 〔(1.10±0.15),(1.00±0.13), P<0.05, P 0.01, respectively〕. Moreover, the mRNA expression of c-fos and c-jun was also significantly higher in the HM than in the LM group(P<0.05). The neointimal hyperplasia in LM and HM groups were more obvious than that in the control group. After 14 days of the balloon injury, the intimal area and intima/media ratio of the low and high dose-methionine-treated animals were increased by 87%( P<0.01), 98%(P<0.05) and 97%(P<0.01), 109%(P<0.01), respectively; luminal areas were also significantly smaller(45% and 55%, P<0.05) as compared to the control animals. Conclusions (1)Hyperhomocysteinemia can exacerbates intimal hyperplasia after denuding injury, making hyperhomocysteinemia a likely new independent risk factor for vascular restenosis after balloon injury. (2)Homocysteine can up-regulate the transcription of c-fos and c-jun in the common carotid artery, this may be one of the mechanisms of neointimal hyperplasia induced by homocysteine in common carotid artery after balloon injury.