丹参多酚盐对动脉内膜增生的影响及其机制研究

The mechanism and effect of salvianolate on the proliferation of vascular intima

目的观察丹参多酚盐对大鼠颈动脉内膜损伤后血管增生的影响,并探讨其机制。方法将18只SD大鼠随机分为假手术组、手术组、丹参多酚盐组,每组6只,颈动脉内膜损伤术后14 d分别检测各组大鼠血清中白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)水平,并取颈动脉切片作病理形态学观察内膜增生情况,测量血管新生内膜厚度(IT)、中膜厚度(MT)并计算IT/MT值,RT-PCR和Western Blot分别测定各组管壁LOX-1m RNA和蛋白的表达变化。结果大鼠颈动脉内膜损伤后14 d可见血管内膜增生,管腔狭窄;与假手术组比较,手术组管壁LOX-1m RNA和蛋白的表达升高,差异具有统计学意义(P均<0.05),血清中促炎因子IL-6、TNF-α水平上升,抗炎因子IL-10、TGF-β水平下降,差异具有统计学意义(P均<0.05);与手术组比较,丹参多酚盐组内膜增生显著减低,血清IL-6、TNF-α水平下降,IL-10、TGF-β水平升高,差异具有统计学意义(P均<0.05),管壁LOX-1 m RNA和蛋白表达水平明显降低,差异具有统计学意义(P均<0.05);丹参多酚盐组与假手术组比较,大鼠颈动脉IT、MT和IT/MT,血清中IL-6、IL-10、TNF-α和TGF-β水平,管壁LOX-1m RNA和蛋白表达水平,差异不具有统计学意义(P均>0.05)。结论丹参多酚盐能有效抑制大鼠颈动脉内膜损伤后内膜的增生,抑制炎症反应,其机制可能与下调增生内膜LOX-1表达有关。

Objective To observe the effect of salvianolate on the proliferation of vascular intima and studymechanism behind. Methods 18 SD rats were randomly divided into sham operation group, operation group,salvianolate group. After operation for 14 days, IL-6, IL-10, TNF-α and TGF-β levels were measured inserums, and pathological morphology of carotid artery sections were observed, including the intimal hyperplasia,intimal thickness (IT), Medium thickness (MT) and calculate IT/MT value. RT-PCR and Western Blot were usedto measure the expression of LOX-1 mRNA and proteins in vascular. Results Intimal hyperplasia and vascularluminal stenosis were observed at 14 days in the rat carotid artery after vascular intimal injury. Compared with shamoperation group, the expression of LOX-1 mRNA and proteins in operation group were increased in vascular walls(P<0.05). IL-6, TNF-α levels in serum were increased, while IL-10, TGF-β levels were decreased (P<0.05).Compared with the operation group, the intimal hyperplasia was significantly decreased in the salvianolate group, aswell as serum IL-6 and TNF-α levels. However, IL-10 and TGF-β levels were increased (P<0.05), and LOX-1mRNA and proteins expression level significantly were decreased (P<0.05). There was no statistic differencebetween salvianolate group and sham operation group in above items (P>0.05). Conclusion Salvianolate caneffectively inhibit the intimal hyperplasia and inflammatory response after carotid artery injury, it may be related tothe downregulation of the expression of LOX-1 in intimal hyperplasia.