目的 探讨白藜芦醇对动脉粥样硬化兔血清中炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α),以及核因子-κB(NF-κB)、丝裂原活化蛋白激酶(MAPK)信号通路的影响,明确白藜芦醇抗动脉粥样硬化的机制.方法 将雄性纯种日本大耳白兔以完全随机区组法分为6组,即正常对照组(对照组,n=10),高脂模型组(高脂组,n=10),白藜芦醇低、中、高剂量组(n均为10),白藜芦醇预防组(预防组,n=10).酶联免疫分析(ELISA)法检测血清炎性指标IL-1 β、IL-6、TNF-α的表达水平,蛋白免疫印迹(Western blot)法检测主动脉组织中NF-κB、p38丝裂原活化蛋白激酶(p38MAPK)、细胞外调解激酶(ERK 1/2)和应激活化蛋白激酶(JNK)的蛋白表达水平.结果 高脂组IL-1β、IL-6、TNF-α浓度均显著高于对照组(P均<0.05).白藜芦醇低、中、高剂量组及预防组IL-1β、IL-6、TNF-α浓度则均低于高脂组(P均<0.01),且此作用呈剂量依赖性.此外,高脂组主动脉组织中NF-κB、p38MAPK、JNK、ERK1/2蛋白磷酸化水平均高于对照组(P均<0.05).白藜芦醇低、中、高剂量组及预防组NF-κB、p38MAPK、JNK蛋白磷酸化水平则均低于高脂组(P均<0.05),ERK1/2蛋白磷酸化水平与高脂组比较差异无统计学意义.结论 白藜芦醇可以降低动脉粥样硬化兔血清炎症因子水平,其作用机制可能与抑制NF-κB、MAPK信号通路的激活有关.
Objective Inflammation serves as the initial pathologic step of cardiovascular diseases including atherosclerosis.Resveratrol possesses many pharmacological properties including antioxidant,cardioprotective and anti-cancer effects.In this study,we investigate the anti-inflammatory effect and mechanisms of resveratrol in an atherosclerotic rabbit model.Methods Rabbit were assigned to six groups (n =10 each):control,high fat diet group,resveratrol low,medium and high dose groups,resveratrol pretreatment group.The serum tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and intedeukin-1β (IL-1β) were analyzed by Enzyme-linked immuno sorbent assay (ELISA).Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades and NF-κB were determined by Western blot.Results Compared with the control group,the expression of serum inflammatory factors IL-1β,IL-6,TNF-α were increased in high-fat group (all P 〈 O.05).Compared with high-fat group,the expressions of IL-6,IL-1β,TNF-α were significantly reduced in resveratrol low,medium,high dose groups and resveratrol pretreatment group (all P 〈 0.01),and this effect is dose-dependent.In addition,the NF-κB,p38MAPK,JNK,ERK1/2 protein phosphorylation in high-fat group were significantly upregulated compared with control group (P 〈0.05),which (except ERK1/2 phosphorylation level) were significantly downregulated in resveratrol treatment group and resveratrol pretreatment group.Conclusion This study indicates that resveratrol .