Astragaloside Ⅳ Regulates Blood Lipid and Inflammatory Factors Through NLRP3 Inflammasome in Early Diabetic Atherosclerosis Rats
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摘要: 目的 探讨黄芪甲苷调节糖尿病动脉粥样硬化早期大鼠血脂及炎症因子的作用及机制。方法 将48只GK大鼠随机分为模型组、阳性药(格列喹酮片联合盐酸贝那普利片)组、黄芪甲苷低剂量组和黄芪甲苷高剂量组，每组12只，均为高脂饲料饲养。12只Wistar大鼠作为空白对照。给药组分别灌胃格列喹酮片(10 mg/kg)及盐酸贝那普利片(10 mg/kg)和黄芪甲苷(20、40 mg/kg)，对照组及模型组灌胃生理盐水，每日1次，连续6周。动物体质量及血糖被监测。采用生化法测定大鼠血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)的含量；HE染色法观察大鼠腹主动脉病理形态；ELISA法测定大鼠腹主动脉IL-6、IL-10、CRP、TNF-α的含量；Western blot法检测大鼠腹主动脉NLRP3、ASC、Caspase-1蛋白的表达。结果 与模型组相比，黄芪甲苷高、低剂量组均可明显改善大鼠腹主动脉病变, 降低大鼠血糖及血清TC、TG、LDL水平，升高HDL水平，降低腹主动脉IL-6、CRP、TNF-α水平，提高IL-10水平, 下调NLRP3、ASC、Caspase-1蛋白的表达(P＜0.05~0.000 1)。结论 黄芪甲苷可调节糖尿病动脉粥样硬化早期大鼠的血脂及炎症状态，机制与调控NLRP3炎性小体相关蛋白的表达密切相关。Abstract: OBJECTIVE To investigate the effect and mechanism of astragaloside Ⅳ in regulating blood lipid and inflammatory factors in early diabetic atherosclerosis rats.METHODS Forty-eight GK rats were randomly divided into model group, positive drugs (gliquantel positive drug combined with benazepril hydrochloride tablets) group, astragaloside Ⅳ low-dose and high-dose groups, 12 rats in each group were fed with high-fat diet. 12 Wistar rats were used as blank control. The administration groups were intragastrically administrated Gliquanone tablets (10 mg/kg), combined with Benazepril hydrochloride tablets (10 mg/kg), astragaloside Ⅳ (20, 40 mg/kg), respectively. The control group and model group were intragastrically given normal saline once a day for 6 weeks. The rat body weight and blood sugar were monitored. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) in serum of rats were determined by biochemical method. The pathological morphology of abdominal aorta of rats was observed by HE staining. The contents of IL-6, IL-10, CRP and TNF-α in rat abdominal aorta were determined by ELISA. The protein expression levels of NLRP3, ASC and Caspase-1 in rat abdominal aorta were detected by Western blot.RESULTS Compared with model group, astragaloside Ⅳ high and low dose groups significantly improved atherosclerosis, decreased blood glucose, levels of serum TC, TG, LDL, increased HDL level, decreased the levels of IL-6, CRP, TNF-α in abdominal aorta, increased IL-10 level, and down-regulated the protein expressions of NLRP3, ASC and Caspase-1 (P < 0.05, P < 0.01, P < 0.001, P < 0.000 1).CONCLUSION Astragaloside Ⅳ can regulate blood lipid and inflammatory status in early diabetic atherosclerosis rats, and the mechanism is closely related to the regulation of NLRP3 inflammasome related protein expression.
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Key words:
- astragaloside Ⅳ /
- diabete /
- NLRP3 /
- blood lipid /
- inflammatory factors
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图 1 黄芪甲苷对糖尿病动脉粥样硬化大鼠体质量、空腹血糖的影响
注：与对照组比较，####P<0.000 1;与模型组比较，*P<0.05，**P<0.01，****P＜0.000 1。
图 2 黄芪甲苷对糖尿病动脉粥样硬化大鼠血清TC、TG、HDL及LDL含量的影响
注：与对照组比较，###P＜0.001，####P<0.000 1;与模型组比较，*P<0.05，**P<0.01，***P＜0.001，****P＜0.000 1。
图 4 黄芪甲苷对糖尿病动脉粥样硬化大鼠腹主动脉IL-6、IL-10、CRP、TNF-α含量的影响
注：与对照组比较，####P<0.000 1;与模型组比较，***P＜0.001，****P＜0.000 1。
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