首页|基于AMPK/PGC1α信号通路探究降脂逐瘀汤对动脉粥样硬化大鼠脂代谢的影响

基于AMPK/PGC1α信号通路探究降脂逐瘀汤对动脉粥样硬化大鼠脂代谢的影响

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目的:基于AMPK/PGC1α信号通路探究降脂逐瘀汤对动脉粥样硬化(AS)大鼠脂代谢的影响.方法:高脂饲料喂养及腹腔注射维生素D3诱导建立AS大鼠模型,随机分为模型组、降脂逐瘀汤(3.75 g/kg)低剂量组、降脂逐瘀汤(7.5 g/kg)中剂量组、降脂逐瘀汤(15 g/kg)高剂量组、降脂逐瘀汤(15 g/kg)高剂量+盐酸多索啡(AMPK抑制剂,0.2 mg/kg)组,每组12只,另取12只正常SD大鼠喂养普通饮食及腹腔注射生理盐水作为对照组.经降脂逐瘀汤和盐酸多索啡分组干预处理各组大鼠后,检测大鼠甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平;HE染色检测大鼠主动脉组织病理变化;油红O染色检测各组大鼠主动脉和肝脏脂质沉积;酶标仪测定大鼠血清炎症因子IL-8、IL-1β、IL-18水平;免疫印迹法检测大鼠主动脉组织AMPK/PGC1α通路蛋白表达.结果:与对照组相比,模型组大鼠主动脉组织发生严重病理损伤,主动脉和肝脏组织中有大量脂质沉积,肝脏脂肪变性严重,血清LDL-C、TC、TG、IL-8、IL-1β、IL-18水平显著升高(P<0.05),血清HDL-C水平、主动脉组织p-AMPK/AMPK与PGC1α蛋白表达显著降低(P<0.05).与模型组相比,降脂逐瘀汤各剂量组大鼠主动脉组织病理损伤、主动脉脂质沉积和肝脏脂肪变性症状均减轻,血清LDL-C、TC、TG、IL-8、IL-1β、IL-18水平均降低(P<0.05),血清HDL-C水平、主动脉组织p-AMPK/AMPK与PGC1α蛋白表达均升高(P<0.05),且呈剂量依赖性(P<0.05);与降脂逐瘀汤高剂量组相比,降脂逐瘀汤高剂量+盐酸多索啡组大鼠主动脉组织病理损伤、主动脉脂质沉积和肝脏脂肪变性症状加重,血清LDL-C、TC、TG、IL-8、IL-1β、IL-18水平升高(P<0.05),血清HDL-C水平、主动脉组织p-AMPK/AMPK与PGC1α蛋白表达降低(P<0.05).结论:降脂逐瘀汤可通过激活AMPK/PGC1α信号抵抗炎症发生发展,减轻大鼠主动脉组织病理损伤、主动脉脂质沉积和肝脏脂肪变性症状,改善AS大鼠脂代谢.
Impact of Jiangzhi Zhuyu Decoction on lipid metabolism in atherosclerotic rats based on AMPK/PGC1α signaling pathway
Objective:To explore impact of Jiangzhi Zhuyu Decoction on lipid metabolism in atherosclerotic(AS)rats based on AMPK/PGC1α signaling pathway.Methods:AS model rats were induced and established by high-fat diet feeding and intraperitoneal injection of vitamin D3,and randomly grouped into model group,low-dose Jiangzhi Zhuyu Decoction(3.75 g/kg)group,medium-dose Jiangzhi Zhuyu Decoction(7.5 g/kg)group,high-dose Jiangzhi Zhuyu Decoction(15 g/kg)group,high-dose Jiangzhi Zhuyu Decoc-tion(15 g/kg)+doxorphine hydrochloride(AMPK inhibitor,0.2 mg/kg)group,with 12 rats in each group,another 12 normal SD rats were fed with normal diet and intraperitoneally injected with normal saline as control group.After Jiangzhi Zhuyu Decoction and doxor-phine hydrochloride were grouped to intervene rats in each group,levels of triacylglycerol(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)in rats were measured;HE staining was used to detect pathological changes of rat aorta;oil red O staining was used to detect lipid deposition in aorta and liver of rats in each group;microplate reader was used to detect levels of serum inflammatory mediators IL-8,IL-1β and IL-18;Western blot was used to detect expression of AMPK/PGC1α pathway protein in rat aorta.Results:Compared with control group,model group had severe pathological damage to aorta tissue,a large amount of lipid deposition in aorta and liver tissue,and severe liver steatosis,serum LDL-C,TC,TG,IL-8,IL-1β and IL-18 levels were obviously increased(P<0.05),serum HDL-C level,aortic tissue p-AMPK/AMPK and PGC1α protein expression were obviously decreased(P<0.05).Compared with model group,aortic tissue pathological damage,aortic lipid deposition and hepatic steatosis symptoms of rats in Jiangzhi Zhuyu Decoction groups were alleviated,serum LDL-C,TC,TG,IL-8,IL-1β and IL-18 were obviously decreased(P<0.05),serum HDL-C level,aortic tissue p-AMPK/AMPK and PGC1α protein expres-sions were obviously increased(P<0.05),which in a dose-dependent manner(P<0.05);compared with high-dose Jiangzhi Zhuyu Decoction group,aortic tissue pathological damage,aortic lipid deposition and liver steatosis were aggravated in high-dose Jiangzhi Zhuyu Decoction+doxorphine hydrochloride group,serum LDL-C,TC,TG,IL-8,IL-1β,and IL-18 levels were obviously increased(P<0.05),serum HDL-C level,aortic tissue p-AMPK/AMPK and PGC1α protein expressions were obviously decreased(P<0.05).Conclusion:Jiangzhi Zhuyu Decoction can resist occurrence and development of inflammation by activating AMPK/PGC1α signal,alleviate aortic pathological damage,aortic lipid deposition and liver steatosis symptoms in rats,and improve lipid metabolism in AS rats.

AMPK/PGC1αJiangzhi Zhuyu DecoctionAtherosclerosisLipid metabolism

张志勇、田辉

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武汉市中医医院,武汉 430014

AMPK/PGC1α 降脂逐瘀汤 动脉粥样硬化 脂代谢

武汉市卫生健康委2021年度中医类科研项目

WZ21B05

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(9)