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目的探讨小檗碱预防颈动脉粥样硬化形成的作用机制。方法将24只雄性新西兰大白兔随机分为3组:正常组、颈动脉粥样硬化组(模型组)、小檗碱预防组(小檗碱组),每组各8只。正常组予普通饮食5周;模型组和小檗碱组给予高脂饲料喂养1周后行右侧颈动脉内膜空气干燥术,术后继续高脂饲料喂养4周;小檗碱组在给予高脂饲料喂养的同时每日灌服小檗碱。第5周取右侧颈动脉组织行HE染色观察颈动脉病理改变、行核因子-κB(Nuclear factor kappa B,NF-κB)免疫组织化学染色半定量检测NF-κB的活性,RT-PCR法检测NF-κBp65-mRNA、VCAM-1 mRNA。结果模型组颈动脉有明显的动脉粥样硬化斑块形成;小檗碱组的内膜轻度增厚,内膜下有少量泡沫细胞形成。小檗碱组NF-κBp65阳性细胞数密度高于正常组(P<0.01),明显低于模型组(P<0.01)。小檗碱组NF-κBp65/β-actin、VCAM-1/β-actin扩增带吸光度值比值高于正常组(0.42±0.05比0.18±0.04;0.61±0.11比0.20±0.04,P<0.01),而明显低模型组(0.42±0.05比0.66±0.10;0.61±0.11比0.81±0.11,P<0.01)。NF-кB活性与VCAM-1呈显著正相关(r=0.926P<0.01)。结论小檗碱预防家兔颈动脉粥样硬化可能通过抑制NF-κB活性,降低VCAM-1表达而起作用。
Objective To explore the mechanism of berberine in preventing the formation of carotid atherosclerosis. Methods Twenty-four male New Zealand white rabbits were randomly divided into 3 groups: normal group, carotid atherosclerosis group (model group) and berberine preventive group (berberine group), 8 in each group. The rats in the model group and the berberine group were given the high-fat diet for 1 week, then the right carotid intima was air-dried, and the high-fat diet was continued for 4 weeks after the model diet. The rats in the berberine group were given high fat Feed berberine daily while feeding. At the fifth week, the right carotid arteries were taken to observe the pathological changes of the carotid arteries by HE staining. The activity of NF-κB was detected by immunohistochemical staining of nuclear factor kappaB (NF-κB), RT-PCR NF-κBp65-mRNA and VCAM-1 mRNA were detected. Results The carotid arteries in the model group had obvious atherosclerotic plaque formation. The berberine group had mild thickening of the intima and a small amount of foam cells under the intima. The number of NF-κBp65-positive cells in berberine group was significantly higher than that in normal group (P <0.01), which was significantly lower than that in model group (P <0.01). Compared with normal group, the ratios of absorbance of NF-κBp65 / β-actin and VCAM-1 / β-actin in berberine group were higher than those in normal group (0.42 ± 0.05 vs 0.18 ± 0.04; 0.61 ± 0.11 vs 0.20 ± 0.04, P <0.01) (0.42 ± 0.05 vs. 0.66 ± 0.10; 0.61 ± 0.11 vs. 0.81 ± 0.11, P <0.01). There was a significant positive correlation between NF-кB activity and VCAM-1 (r = 0.926P <0.01). Conclusion Berberine can prevent carotid atherosclerosis in rabbits by inhibiting the activity of NF-κB and decreasing the expression of VCAM-1.