【摘要】 目的探讨人参皂苷Re(ginsenoside Re)对球囊损伤所致血管新生内膜增生的作用及其分子机制。方法利用雄性SD大鼠建立球囊损伤致颈动脉内膜增生模型,模型制备完成后后将40只大鼠随机分为5组:人参皂苷Re 6、12、24 mg·kg-1·d-1剂量组、模型组及假手术组,每组8只,术后次日腹腔注射给药,模型组与假手术组给予等体积生理盐水,连续给药14 d后取损伤侧颈动脉行HE染色,观察颈动脉血管腔狭窄程度并计算新生内膜面积及内膜/中膜面积的比值;实时荧光定量聚合酶链反应法检测血管壁丝裂原活化蛋白激酶磷酸酶-1(mitogen-activated protein kinase phosphatase-1,MKP-1)mRNA的表达;免疫组织化学法检测血管壁丝裂原活化蛋白激酶磷酸酶-1和磷酸化细胞外信号调节激酶1/2(phosphorylation extracellular signal-regulated kinase,p ERK1/2)蛋白质的表达。结果与假手术组比较,模型组血管腔明显狭窄(P<0.01),血管壁磷酸化细胞外信号调节激酶1/2蛋白质表达明显上调,而丝裂原活化蛋白激酶磷酸酶-1 mRNA及蛋白质表达却明显下调;人参皂苷Re各给药组均能改善球囊损伤所致的血管狭窄,使血管壁新生内膜面积、新生内膜/中膜面积的比值明显减小(P<0.05),并逆转球囊损伤后磷酸化细胞外信号调节激酶1/2蛋白质表达(P<0.05)和丝裂原活化蛋白激酶磷酸酶-1 mRNA及蛋白质表达(P<0.05,P<0.01)。结论人参皂苷Re可抑制球囊损伤所致的颈动脉狭窄,其分子机制与抑制ERK通路有关。更多还原

【Abstract】 OBJECTIVE To investigate the inhibitory effect of ginsenoside Re on vascular neointimal hyperplasia induced by balloon-injury and probe its molecular mechanism in rats. METHODS The rat carotid artery neointimal hyperplasia model was established by rubbing the endothelia with a balloon in male Sprague-Dawley rats,then animals were intrapritoneally injected with distilled water in model group and sham operation group or with ginsenoside Re 6,12 and 24 mg · kg- 1·d- 1in other endothelia rubbed groups. After 14 consecutive days,the injuried artery was taken for H&E staining,the histopathological observation and detecting the neointimal area as well as the ratio of neointimal area / media area were taken to evaluate the vescular intimal hyperplasia level. For probing the molecular mechanism,the expression of mitogen-activated protein kinase phosphatase-1( MKP-1) was detected at the transcript levels by real time RT-PCR,and the protein expressions of MKP-1 and phosphorylation extracellular signal-regulated kinase 1 /2( p ERK1 /2) were examined by immunohistochemistry and analyzed with Image-Pro Plus. RESULTS Compared with the endothelia rubbing model group,ginsenoside Re 6,12,24 mg·kg- 1·d- 1medications significantly improved the histopathological changes induced by baloon-injury,decreased the elevated neointimal area and the ratio of neointimal area / media area induced by baloon-injury;ginsenoside Re administration could also down-regulate the elevated p ERK1 /2 protein expression,and significantly up-regulated the decreased MPK-1 mRNA and protein expressions induced by baloon-injury. CONCLUSION Ginsenoside Re inhibits the vascular neointimal hyperplasia induced by baloon- injury in rats,the molecular mechanism is related to its inhibition effect on ERK signaling.更多还原