人参皂苷Re对球囊损伤大鼠血管内膜增殖及TGF-β1/Smads信号通路的影响

Effects of ginsenoside Re on vascular intimal proliferation in balloon-injuried rats via regulation of TGF-pi/Smads signaling pathway

目的探讨人参皂苷Re(GS-Re)对球囊损伤后大鼠颈动脉内膜增殖及TGF-β1/Smads信号通路的影响。方法 50只清洁级SD大鼠随机分为5组:假手术组,模型组,GS-Re低、中、高剂量(12.5、25.0、50.0 mg/kg)组。除假手术组外,其余组大鼠均采用2F球囊导管建立颈动脉球囊损伤模型,造模后次日开始ig给药,连续给药14 d后取损伤段颈动脉,行HE染色,观察血管形态学改变,用Leica光学显微镜测定血管腔面积(LA)、内膜面积(IA)、中膜面积(MA),并计算IA/MA。利用Real time RT-PCR法、免疫组织化学法分别检测转化生长因子β1(TGF-β1)、Smad2、Smad3的mRNA表达及蛋白水平的变化。结果与假手术组比较,模型组血管腔变窄(P<0.01);与模型组比较,GS-Re中、高剂量组血管内膜增生减轻(P<0.05、0.01)。与假手术组比较,模型组血管壁TGF-β1、Smad2、Smad3 mRNA水平及其蛋白表达均增高(P<0.01);与模型组比较,GS-Re中、高剂量组血管壁TGF-β1、Smad2、Smad3 mRNA水平下调,蛋白表达量也降低(P<0.05)。此外,GS-Re低剂量组血管壁TGF-β1 mRNA水平及p-Smad2蛋白的表达也下调(P<0.01)。结论 GS-Re可通过抑制TGF-β1/Smads通路发挥抑制血管内膜增殖的作用。

Objective To investigate the inhibitory effects ofginsenoside Re on intimal hyperplasia in balloon-injuried rats and further explore the role of TGF-β1/Smads signaling pathway in this protection. Methods Fifty SD rats were randomly divided into five groups, including Sham operation group, model group, ginsenoside Re low, medium, and high-dose groups. The injured model of carotid artery intima was established by 2F balloon catheters in each group except the sham operation group. One day after model was established, animals were daily ig administered with distilled water in model group, Sham operation group, and ginsenoside Re 02.5 mg/kg, 25 mg/kg and 50 mg/kg） groups. Two weeks later, animals were sacrificed and the injured artery was taken for HE staining. The histopathological changes were observed and the lumen area, intima area, and media area as well as the ratio of intimal area/media area were detected. The expression of transforming growth factors β1 （TGF-β1）, SMAD family member 2 （Smad 2） and Smad family member 3 （Smad 3） were measured by real time RT-PCR and immunohistochemistry. Results Compared with the Sham operation group, the vessel cavity in the model group was narrower （P 〈 0.01）; Compared with the model group, the medium and high dose of ginsenoside Re obviously alleviated vascular intimal hyperplasia （P 〈 0.05）. Compared with the Sham operation group, the mRNA and protein expressions levels of TGF-β1, Smad 2, and Smad 3 in model group were higher （P 〈 0.01）, which were obviously decreased in the medium and high-dose ginsenoside Re （P 〈 0.05）. Conclusion Ginsenoside Re could alleviate the vascular neointimal hyperplasia through suppressing the TGF-β1/Smads signaling pathway.