丹参酮抑制大鼠颈动脉损伤后再狭窄的实验研究

目的:观察丹参酮对大鼠颈动脉损伤后再狭窄的防治作用,并探讨其作用机制。方法:雄性SD大鼠随机分为模型组、丹参酮高、中及低剂量组,每组10只。用自制2F球囊对大鼠右侧颈总动脉进行损伤造成颈动脉狭窄模型。术前2 d开始给药,高、中、低剂量组分别灌胃给予丹参酮120,40,13.3 mg.kg^-1.d^-1,给药体积为10 mL.kg^-1,模型组给予等体积的溶媒。给药2周后,取伤侧及对侧颈总动脉做HE染色,光镜下观察动脉形态并用计算机图像分析系统分析动脉内膜面积、中膜面积及内膜/中膜面积,用免疫组化测定增殖细胞核抗原(PCNA)、核因子(NF)-κB及诱导型一氧化氮合酶(iNOS)的表达水平并计算阳性率。结果:损伤动脉内膜面积和内膜/中膜面积显著增加,提示造模成功。与模型组比较,丹参酮低剂组内膜面积、内膜/中膜面积、PCNA阳性指数、NF-КB及iNOS阳性率有所降低,但差异不显著,中剂组和高剂组则效果明显,差异具有显著性(P<0.05)。结论:丹参酮可抑制大鼠颈动脉损伤后再狭窄,这种作用与其抑制平滑肌增殖和炎症作用有关。

Experimental study of effect of tanshinone on artery restenosis in rat carotid injury model

OBJECTIVE: To observe the preventive and therapeutic effect of tanshinone (TA) on artery restenosis in the rat carotid injury model and explor the mechanism. METHOD: Male SD rats were randomly divided into model control group, and low dose, moderate dose and high dose TA groups. Each group had 10 rats. The rats in the high, moderate and low dose groups were respectively fed with TA 120, 40,13.3 mg x kg(-1) x d(-1) by gast rogavage; the rats in the model control group were fed with the same volume solvent. Two days later, the rat's right carotid artery was injuried by balloon dilatation to induce intimal thickening for establishing the restenosis model. After 2 weeks of treatment, the artery was harvested and stained by hematoxylin-elsin (HE) and immunohistochemistry of PCNA, NF-kappaB and iNOS. The morphological changes were checked under microscope. The area of the intimal and medial layer of the vessels, and their ratios were analyzed with image analysis software. The expression level of PCNA, NF-kappaB and iNOS were used as the positive index. RESULT: The intimal area and intima-to-media ratio of the injuried artery increased obviously, suggesting the model was successful. Compared with the model group, TA significantly decreased the intimal area and intima-to-media ratio (P < 0.05), and also decreased the positive index of PCNA and the positive ratio of NF-kappaB and iNOS (P < 0.05). CONCLUSION: TA can effectively inhibit intimal thickening and inflammation. This result suggestes that TA may play a positive role in the prevention of restenosis after PTCA.