香菇多糖对ApoE^(-/-)小鼠动脉粥样硬化斑块形成及AMPK信号通路的影响

Effects of lentinan on atherosclerotic plaque formation and AMPK signaling pathway in ApoE^(−/−)mice

目的:探讨香菇多糖(LNT)对ApoE^(-/-)小鼠动脉粥样硬化(AS)斑块形成及单磷酸腺苷活化蛋白激酶(AMPK)信号通路的影响。方法:ApoE^(-/-)小鼠分为模型组、立普妥组(5 mg/kg)、LNT低(5 mg/kg)、中(10 mg/kg)、高(20 mg/kg)剂量组,以相似遗传背景的C57BL/6小鼠为对照组。灌胃给药12周后,全自动生化分析仪检测血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)水平;ELISA检测血清IL-6、IL-1β水平;油红O染色观察整体主动脉斑块形成情况;HE染色观察主动脉根部斑块形成情况;蛋白免疫印迹检测主动脉AMPK通路蛋白表达。结果:与对照组比较,模型组血清TC、TG、LDL-C、IL-6、IL-1β水平、主动脉斑块面积、主动脉根部斑块面积、主动脉组织NLRP3、IL-6、IL-1β表达显著升高,主动脉组织p-AMPK/AMPK表达和血清HDL-C水平降低(P<0.05);与模型组比较,立普妥组、LNT中、高剂量组TC、TG、LDL-C、IL-6、IL-1β、主动脉斑块面积、主动脉根部斑块面积、主动脉组织NLRP3、IL-6、IL-1β表达显著降低,主动脉组织p-AMPK/AMPK表达和血清HDL-C水平显著升高,且LNT各剂量组间差异有统计学意义(P<0.05);立普妥组与LNT高剂量组差异无统计学意义(P>0.05)。结论:LNT可能通过激活AMPK通路抑制AS小鼠炎症反应和AS斑块形成。

Objective:To investigate effects of lentinan(LNT)on atherosclerosis(AS)plaque formation and adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway in ApoE^(−/−)mice.Methods:ApoE^(−/−)mice were divided into model group,Lipitor group(5 mg/kg),LNT low(5 mg/kg),medium(10 mg/kg),high(20 mg/kg)dose groups,C57BL/6 mice of similar genetic background were as control group.After 12 weeks of intragastric administration,automatic biochemical analyzer was used to detect serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein(LDL-C)and high-density lipoprotein(HDL-C)levels;serum levels of IL-6 and IL-1βwere detected by ELISA;oil red O staining was used to observe overall aortic plaque formation;HE staining was used to observe formation of plaque in aortic roots;AMPK pathway proteins expressions in aortawas were detected by Western blot.Results:Compared with control group,serum TC,TG,LDL-C,IL-6,IL-1βlevels,aortic plaque area,aortic root plaque area,aortic tissue NLRP3,IL-6,IL-1βexpressions were significantly increased in model group,p-AMPK/AMPK expression in aortic tissue and serum HDL-C level were reduced significantly(P<0.05);compared with model group,TC,TG,LDL-C,IL-6,IL-1β,aortic plaque area,aortic root plaque area,aortic tissues NLRP3,IL-6 and IL-1βexpressions were reduced significantly in Lipitor group and medium,high dose LNT groups,p-AMPK/AMPK expression in aortic tissue and serum HDL-C level were increased significantly,difference between each dose of LNT was statistically significant(P<0.05);there was no significant difference between Lipitor group and LNT high-dose group(P>0.05).Conclusion:LNT may inhibit inflammatory response and formation of AS plaques in AS mouse by activating AMPK pathway.