异甘草素对颈动脉血管内膜增生炎性细胞因子抑制作用及机制探讨

Inhibitory effect of isoliquiritigenin on inflammatory factors of carotid artery intimal hyperplasia and the mechanism

目的研究异甘草素抑制球囊损伤后血管内膜增生及其可能机制。方法 50只SD大鼠随机分为对照组、模型组、异甘草素组(50、100、200 mg/kg)。对照组和模型组每天给予3 ml生理盐水灌胃,异甘草素组每天分别给予3 ml的药物灌胃。术后14、28 d取大鼠颈总动脉行HE染色,观察颈总动脉病理形态变化,并测量内膜的面积(area of intima,IA)、中膜的面积(area of membrane,MA)及内膜/中膜面积比(IA/MA)。免疫组化技术和Western blot检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、Toll样受体4(Toll-like receptor 4,TLR4)、核因子-κB(nuclear factor-κB,NF-κB)p65表达变化结果。结果与对照组比较,模型组14、28 d内膜的面积、内膜/中膜的面积比明显增加(P<0.05)。颈总动脉的PCNA、TLR4、NF-κB p65的表达明显增加(P<0.05)。药物低剂量组和高剂量组与模型组比较,14、28 d内膜的面积、内膜/中膜的面积比明显减少(P<0.05)。颈总动脉的PCNA、TLR4、NF-κB p65的表达明显降低(P<0.05)。结论异甘草素能通过TLR4介导的NF-κB通路抑制血管内膜增生,降低球囊损伤后血管再狭窄及其发生率。

Objective To investigate the effect of isoliquiritigenin on intimal hyperplasia after balloon injury and its possible mechanism. Methods Fifty SD rats were randomly divided into the control group, model group and isoliquiritigenin group （50, 100, 200 mg/kg）. The control group and model group were given 3ml normal saline daily, while the isoliquiritigenin group was given 3 ml gavage daily. The pathological changes of the common carotid artery were observed using HE staining 14 days and 28 days after operation. The intima area （IA）, the membrane area （MA） and the ratio of intima/medial area （IA/MA） were measured. The expressions of proliferating cell nuclear antigen （PCNA）, Toll-like receptor 4 （TLR4） and nuclear factor-κB （p65） were detected by immunohistochemistry and Western blot. Results The area of the membrane and that of the intima/medial membrane increased significantly in the model group at 14 days and 28 days compared with the sham operation group （P〈0.05）. The expressions of PCNA, TLR4 and NF-κB p65 in the carotid artery were significantly increased （P〈0.05）. The area of the membrane and that of the intima/medial membrane were significantly decreased in the low dose group and in the high dose group at 14 days and 28 days compared with the model group （P〈0.05）. The expressions of PCNA, TLR4 and NF-κB p65 in the common carotid artery were significantly decreased （P〈0.05）. Conclusion Isoliquiritigenin can inhibit the proliferation of vascular endothelium through the TLR4-mediated NF-κB pathway and decrease the incidence of vascular restenosis after balloon injury.