大黄蛰虫丸通过NF-κB信号通路调节动脉粥样硬化大鼠血脂及炎症相关指标水平

Rhubarb stinging insect pill regulates blood lipids and inflammation related indexes level through NF-κB signalling pathway in atherosclerotic rats

目的探究大黄蛰虫丸(DHZCW)调控核转录因子(NF)-κB信号通路对动脉粥样硬化(AS)大鼠血脂及炎症相关指标水平的影响及机制。方法60只SD大鼠随机抽取12只作为NC组,余48只通过腹腔注射大剂量维生素(Vit)D3的方式构建AS大鼠模型,并将其随机分为AS组、DHZCW低、中、高剂量组,每组12只。其中DHZCW低、中、高剂量组分别予以1.0、2.0、3.0 g/kg DHZCW灌胃,NC组及AS组均予以等量生理盐水灌胃。观察各组1、3、7 w时的体质量变化及7 w时血管内皮组织形态变化,比较各组血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α水平及p-p65、p65、p-NF-κB抑制蛋白(IκB)α、IκBα蛋白表达。结果在3、7 w时,AS组、DHZCW各剂量组体质量均较NC组明显减少(P<0.05)。在7 w时,DHZCW各剂量组体质量均较AS组明显增加,DHZCW高、中剂量组体质量较DHZCW低剂量组明显降低(P<0.05)。AS组血清TG、TC、LDL-C、IL-1β、IL-6、TNF-α水平及p-p65/p65、p-IκBα/IκBα比值均较NC组明显增加,HDL-C水平较NC组明显减少(P<0.05)。DHZCW各剂量组血清TG、TC、LDL-C、IL-1β、IL-6、TNF-α水平及p-p65/p65、p-IκBα/IκBα比值均较AS组明显减少,HDL-C水平较AS组明显增加(P<0.05);且DHZCW中、高剂量组血清TG、TC、LDL-C、IL-1β、IL-6、TNF-α水平及p-p65/p65、p-IκBα/IκBα比值均较DHZCW低剂量组明显减少,HDL-C水平较DHZCW低剂量组明显增加(P<0.05)。结论DHZCW可通过抑制NF-κB通路降低AS大鼠血脂水平及炎症反应,发挥抗AS的作用。

Objective To investigate the effects and mechanisms of rhubarb stinging insect pill(DHZCW)regulating nuclear transcription factor(NF)-κB signalling pathway on the levels of blood lipids and inflammation-related indexes level in atherosclerotic(AS)rats.Methods Twelve of the 60 SD rats were randomly selected as the NC group,and the remaining 48 rats were injected intraperitoneally with a high dose of vitamin(Vit)D3 to construct the AS rat model,and rats were randomly divided into the AS group,the DHZCW low,medium,and high dose groups,with 12 rats in each group.The DHZCW low,medium and high dose groups were given 1.0,2.0 and 3.0 g/kg DHZCW by gavage respectively,while the NC group and the AS group were given the same amount of saline by gavage.The changes of each group in body mass at 1,3 and 7 w and the morphology of vascular endothelial tissue at 7 w were observed,and the levels of serum triacylglycerol(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),interleukin(IL)-1β,IL-6,tumour necrosis factor(TNF)-αand p-p65,p65,p-NF-κB-inhibitory protein(IκB)α,IκBαprotein expressions were compared among groups.Results At 3 and 7 w,the body mass of the AS and DHZCW dose groups was significantly reduced compared with that of the NC group(P<0.05).At 7 w,the body mass of DHZCW dose groups was significantly increased compared with that of AS group,the body mass of DHZCW high and medium dose groups was significantly lower than that of DHZCW low dose group(P<0.05).The levels of serum TG,TC,LDL-C,IL-1β,IL-6,TNF-αand the ratios of p-p65/p65 and p-IκBα/IκBαin the AS group were significantly higher than those in the NC group,and the level of HDL-C was significantly lower than that in NC group(P<0.05).The levels of serum TG,TC,LDL-C,IL-1β,IL-6,TNF-αand the ratios of p-p65/p65 and pIκBα/IκBαin the DHZCW dose groups were significantly lower than those in the AS group,and the level of HDL-C was significantly higher than that in the AS group(P<0.05);the levels of serum TG,TC,LDL-C,IL-1β,IL-6,TNF-αand the ratios of pp65/p65 and pIκBα/IκBαwere significantly lower in the DHZCW middle and high dose groups than those in DHZCW low dose group,and the level of HDL-C was significantly higher than that in DHZCW low dose group(P<0.05).Conclusions DHZCW could inhibit NF-κB pathway and reduce blood lipid level and inflammation in AS rats to exert anti-AS effects.