中药赤芍对损伤介导的内膜增殖及MKP-1基因表达的影响

Effect of Radix Paeoniae Rubra on intimal proliferation and expression of MKP-1 mRNA after rabbit carotid artery injury

目的:观察赤芍对高脂喂养兔颈动脉球囊损伤后丝裂素活化蛋白激酶磷酸酶-1(MKP-1)mRNA表达、血管紧张素Ⅱ(AgⅡ)激活及内膜增殖的影响。方法:新西兰白兔随机分为对照及赤芍组,各组均饲喂高脂饲料(普通饲料+2%胆固醇+5%猪油)。赤芍组按剂量给予赤芍提取物,高、中、低剂量组相当于生药75、50、25g.kg-1.d-1。球囊损伤颈总动脉内膜建立模型,放射免疫测定血浆AgⅡ水平、测定血管张力、免疫组化染色及形态学测定、RT-PCR检测MKP-1 mRNA表达。结果:与对照组比较,赤芍组AgⅡ水平降低(P<0.05);血管对AgⅡ的收缩反应减弱(P<0.05);增生内膜面积、增生内膜面积/中膜面积显著减少(P<0.05或P<0.01);MKP-1 mRNA表达显著增高(P<0.05或P<0.01)。结论:赤芍降低血浆中的AgⅡ水平,减低血管环对AgⅡ的收缩反应性,增加高脂喂养兔颈动脉球囊损伤后MKP-1 mRNA表达,并减轻内膜增殖程度。表明内膜增殖程度的减低与赤芍抑制RAS激活,并阻断MAPK信号通路有关。

Objective：To observe the effect of Radix Paeoniae Rubra on intimal proliferation ,activating of angiotensin Ⅱ （Ag ） and expression of Mitogen-activated protein kinase phosphatase-1（MKP-1） after carotid artery balloon injury in cholesterol-fed rabbits.Methods： Male rabbits were randomly divided into Radix Paeoniae Rubra（PPR） groups： high dose group （75, 50, 25g·kg^-1·d ^-1; n=8）, middle dose group（2g·kg^-1·d^-1）,low dose group（1g·kg^-1·d^-1; n=8） and control group. Both groups received high fat forage （2% cholesterol ＋ 5% lard）. Balloon injury of carotid artery was performed. Carotid artery were harvested at the end of 10 weeks. Expression level of Ag Ⅱ was measured by radioimmunoassay.MKP-1 expression was determined by RT- PCR. Immunohistochemical staining and morphological detection were adopted. Results： Compare with control group, expression of Ag Ⅱ decreased obviously （ P〈0.05 ）,contractile response to Ag Ⅱ weakened （ P〈0.05 ） ,area of intimal proliferation reduced（P〈0.05,P〈0.01） ,MKP-1 mRNA expression increased（P〈0.05,P〈0.01） in PPR groups .Conclusions： Radix Paeoniae Rubra decreased Ag Ⅱ level in plasma, weakened contractile response to Ag Ⅱ ,increased MKP-1 mRNA expression, and modestly reduced intimal proliferation. The reduced degree of infimal proliferation might be partly attributed to Radix Paeoniae Rubra＇s inhibiting activation of RAS and blocking MAPK signal path.