NF-κB/SREBPs信号通路在右归丸抗大鼠动脉粥样硬化中的调节作用

Effects of Yougui Pill by NF-κB/SREBPs Signaling Pathway in Anti-atherosclerosis in Rats

目的利用右归丸治疗动脉粥样硬化大鼠模型,观察右归丸对于模型大鼠炎性因子与血脂代谢的变化,探讨NF-κB/SREBPs信号通路在右归丸抗大鼠动脉粥样硬化中的调节作用。方法 SD大鼠40只,随机分为正常组、模型组、右归丸组和阿托伐他丁组,利用高脂饮食喂养加维生素D3腹腔注射造模,分别给予右归丸和阿托伐他丁混悬液灌胃,检测血清中脂类物质含量,炎性因子IL-1β、IL-6、TNF-α的含量,观察主动脉血管壁形态学变化及RT-PCR检测大鼠主动脉组织TLR4、NF-κB p65、SREBP1-c和ABCA1基因的表达变化。结果与正常组比较,模型组、右归丸组和阿托伐他汀组中血清TG、TC、LDL-C含量显著升高(P<0.01),HDL-C含量显著降低(P<0.01),而经右归丸和阿托伐他汀治疗后,两组TC及LDL-C的增高程度明显低于模型组(P<0.05);模型组大鼠主动脉血管内膜出现增厚,并伴有粥样斑块形成;右归丸组和阿托伐他汀组主动脉血管内膜增厚程度较模型组低,斑块面积减小,平滑肌细胞较模型组整齐;与正常组比较,模型组、右归丸组和阿托伐他汀组中血清IL-1β、IL-6、TNF-α含量显著升高(P<0.01),而经治疗后两组IL-1β、IL-6、TNF-α的增高程度明显低于模型组(P<0.01);大鼠主动脉TLR4、NF-κB p65、SREBP1-c和ABCA1的mRNA表达在模型组显著升高(P<0.01),而经右归丸和阿托伐他汀治疗后的表达明显低于模型组(P<0.05)。结论右归丸可能通过抑制NF-κB活性减少SREBP1c mRNA表达,减少ABCA1mRNA表达,降低胆固醇从组织细胞中流出,防止泡沫细胞的形成;另一方面右归丸通过抑制NF-κB活性减少炎症因子的释放来防治动脉粥样硬化。

Objective To observe the effects of Yougui pill on inflammatory factors and blood lipid metabolism in rats with atherosclerosis,and to explore the regulatory effect of NF-κB/SREBPs signaling pathway on atherosclerosis in rats.Methods 40 SD rats were randomly divided into normal group,model group,Yougui pill group and Atorvastatin group.Models were established by intraabdominal injection of vitamin D3 and high-fat diet.The serum lipid content,inflammatory factors interleukin-1β(IL-1β),IL-6,tumor necrosis factor α(TNF-α) contents were tested.The morphological changes of aortic wall were observed and the expression of toll-like receptors-4(TLR4),nuclear factor kappa-B(NF-κB)p65,SREBP1c and ABCA1 genes in rat aorta were detected by RT-PCR.Results Compared with normal group,the levels of serum TG,TC,LDL-C and HDL-C in model group,Yougui pill group and Atorvastatin group were significantly higher than those in model group(P<0.01),while the levels of TC and LDL-C in the two groups were significantly lower than those in model group(P<0.05).The intima of aortic vessels in model group was thickened and accompanied by atheromatous plaque formation,and the thickening degree of aortic intima in Yougui pill group and Atorvastatin group was lower than that in model group,the plaque area was decreased,and the smooth muscle cells were neatly higher than those in model group.Compared with normal group,the levels of serum IL-1β and IL-6,TNF-α in Yougui pill group and Atorvastatin group were significantly higher than those in normal group(P<0.01),while the levels of IL-1β and IL-6,TNF-α in the two groups were significantly lower than those in model group after treatment(P<0.01).The mRNA expression of TLR4,NF-κB p65,SREBP1 and ABCA1 in rat aorta was significantly increased in model group,but significantly lower than that in model group after treatment with Yougui pill and Atorvastatin(P<0.05).The expression of SREBP1 and SREBP1 in model group was significantly lower than that in model group(P<0.05).Conclusion Yougui pill may reduce the expression of SREBP1c mRNA,decrease the expression of ABCA1 mRNA,reduce the outflow of cholesterol from tissue cells and prevent the formation of foam cells by inhibiting the activity of NF-κB,on the other hand,Yougui pill can prevent atherosclerosis by inhibiting the activity of NF-κB and reducing the release of inflammatory factors.