摘要
目的 ：通过观察丹参酮Ⅱ A对Apoe基因敲除（ApoE-/-）小鼠主动脉肿瘤坏死因子-α（TNF-α）/p38丝裂原活化蛋白激酶（p38MAPK）/血清核因子-κ B（NF-κ B）/视黄醇结合蛋白（RBP4）信号通路变化,探讨丹参酮Ⅱ A对动脉粥样硬化炎症反应过程的影响及其作用机制。方法 ：将20只ApoE-/-小鼠随机分为模型组、丹参酮Ⅱ A组,每组10只,空白对照组选取具有相同遗传背景的同龄野生型C57BL/6J小鼠10只;模型组与丹参酮Ⅱ A组均给予高脂饲料喂养8周,空白对照组给予普通饲料喂养;丹参酮Ⅱ A组每日灌胃丹参酮Ⅱ A（30 mg/kg）,空白对照组与模型组给予等量生理盐水灌胃,8周后,分离3组小鼠血清,分离主动脉,分别保存于4%多聚甲醛和-80℃冰箱。Elisa法检测小鼠血清TNF-α、RBP4水平变化,全自动生化分析仪检测血清中TG、TC、HDL-C、LDL-C水平,HE染色法观察主动脉组织形态学变化,Western blot法检测TNF-α、p38MAPK、NF-κ B、RBP4蛋白表达,RT-PCR法检测主动脉TNF-α、NF-κ B、RBP4基因表达情况。结果 ：与空白对照组相比,模型组小鼠血清中TG、TC、LDL-C水平显著升高（P〈0.05）,HDL-C水平显著降低（P〈0.05）;主动脉管腔内可见较大的AS斑块形成;TNF-α、p38MAPK、NF-κ B、RBP4蛋白和TNF-α、NF-κ B、RBP4基因m RNA水平显著升高（P〈0.05）。与模型组相比,丹参酮Ⅱ A组TG、TC、LDL-C水平显著降低（P〈0.05）,HDL-C水平显著升高（P〈0.05）;主动脉管腔内的AS斑块面积显著减小;TNF-α、p38MAPK、NF-κ B、RBP4蛋白和TNF-α、NF-κ B、RBP4基因m RNA水平显著降低（P〈0.05）。结论 ：丹参酮Ⅱ A具有调节血脂和抗AS的作用,其机制可能与其参与TNF-α/p38MAPK/NF-κ B/RBP4信号通路调控有关。
Objective ：Through the observation of tanshinoneⅡ-A on Apoe knockout（ApoE-/-）mice aorta TNF-α/p38 MAPK/NF-κ B/RBP4 signaling pathway changes,to explore the effect of tanshinoneⅡ-A on reaction process of atherosclerosis and its mechanism. Methods ：20 ApoE-/-mice were randomly divided into model group,tanshinone A group,10 rats in each group,the control group with the same genetic background from their wild type 10 C57 BL/6 J mice;model group and tanshinoneⅡ-A group were fed with high fat diet for 8 weeks,the control group was given normal diet tanshinone;tanshinoneⅡ-A group gavage of tanshinoneⅡ-A（30 mg/kg）,blank control group and model group were given normal saline. After 8 weeks,three groups of mice serum separation,separation of the aorta were stored in 4% paraformaldehyde and-80 ℃ refrigerator. The changes of Elisa in serum was detected in TNF-α mice,RBP4 level automatic biochemical analyzer detected serum TG,TC,HDL-C,LDL-C level,to observe the morphological changes of aortic tissue by HE staining,the expression of Western detected by blot TNF-α,p38 MAPK NF-κ B,RBP4 protein and RT-PCR were used to detect the aortic TNF-α,NF-κ B,the expression of RBP4 gene. Results ：Compared with the control group,TG,TC,LDL-C level in serum of model mice increased significantly（P〈0.05）,the level of HDL-C was significantly decreased（P〈0.05）;visible large plaque formation in the lumen of aortic AS,TNF-α;p38 MAPK,NF-κ B,RBP4 protein and TNF-α,NF-κ B,RBP4 gene the level of m RNA increased significantly（P〈0.05）. Compared with the model group,tanshinoneⅡ-A group TG,TC,LDL-C were significantly decreased（P〈0.05）,HDL-C level increased significantly（P〈0.05）;aortic lumen of the AS plaque area decreased significantly;TNF-α,p38 MAPK,NF-κ B,RBP4 protein and TNF-α,NF-κ B,RBP4 gene m RNA level significantly reduce（P〈0.05）. Conclusion ：TanshinoneⅡ-A can regulate blood lipid and anti AS effects,its mechanism may participate in the TNF-α/p38 MAPK/NF-κ B/RBP4 signaling pathway regulation.
出处
《辽宁中医药大学学报》
CAS
2018年第1期18-21,共4页
Journal of Liaoning University of Traditional Chinese Medicine
基金
沈阳市科技局计划项目(F15-139-9-03)
