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[摘要]
目的 研究人参皂苷Rg3对大鼠颈动脉损伤后新生内膜增生及平滑肌细胞凋亡的影响。方法 40只SD大鼠随机分为假手术组、模型组和人参皂苷Rg3低、高剂量(5、10 mg/kg)组,各10只,用球囊制备大鼠颈动脉损伤模型,术后次日ig给药,假手术组和模型组给予等量的生理盐水;14 d后取损伤的颈总动脉血管,用苏木精-伊红(HE)染色观察新生内膜组织形态学改变;采用末端脱氧核苷酸转移酶介导的三磷酸脱氧尿嘧啶缺口末端标记(TUNEL)法检测平滑肌细胞凋亡;Western blotting和qRT-PCR法检测损伤血管凋亡基因Fas、抗凋亡基因Bcl-2的表达。结果 与假手术组比较,模型组大鼠血管新生内膜明显增厚,内膜与中膜面积比明显增加,新生内膜区平滑肌细胞凋亡率显著增加,Fas、Bcl-2基因表达明显增加;与模型组比较,人参皂苷Rg3低、高剂量组血管内膜增生明显减轻,内膜与中膜面积比明显下降,新生内膜区平滑肌细胞凋亡率明显增加,损伤血管Fas基因表达水平明显升高,Bcl-2基因表达水平明显降低。结论 人参皂苷Rg3可能通过促进平滑肌细胞的凋亡,从而减轻球囊损伤后血管内膜的增生。
[Key word]
[Abstract]
Objective To investigate the effects of ginsenoside Rg3 on intimal proliferation and apoptosis of vascular smooth muscle cells after vascular injury in rats. Methods Forty Sprague Dawley rats were divided into four groups randomly including Sham operation group, model group, ginsenoside Rg3 low-dose group (5 mg/kg), and ginsenoside Rg3 high-dose group (10 mg/kg). The carotid artery intima injury model was established by inflation balloons. From the next day after modeling, the rats were treated with ginsenoside Rg3 by ig administation in ginsenoside Rg3 groups, and rats in Sham operation group and model group were administered with same amount of normal saline. The injured common carotid arteries were harvested after 14 d and morphological changes of injured arteries were observed by HE staining. Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) was used to detect the apoptosis of smooth muscle cells; Western blotting and qRT-PCR were used to detect the expression of Fas and anti-apoptotic gene Bcl-2. Results Compared with the Sham operation group, the vascular neointima of rats in model group was significantly thicker, and the ratio of intima/media area and the apoptosis rate of neointimal hyperplasia were significantly increased. The expression of apoptosis-related gene Fas and anti-apoptotic gene Bcl-2 was significantly increased. Compared with model group, ginsenoside Rg3 (5 and 10 mg/kg) significantly alleviated vascular intimal hyperplasia, the intima/media area ratio and the expression of Bcl-2 was significantly decreased, and the apoptosis rate of smooth muscle cells in the neointimal area and the expression of Fas in injured vessels were significantly increased. Conclusion Ginsenoside Rg3 can reduce the vascular neointimal hyperplasia induced by balloon injury with the possible underlying mechanism to promote the apoptosis of smooth muscle cells.
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[基金项目]
贵州省科技合作计划项目(黔科合LH字7464号);贵州省中医药管理局中医药、民族医药科学技术研究课题(QZYY2017-007)