电针对快速衰老小鼠肝脏自噬及脂质代谢的影响

Effects of electroacupuncture on autophagy factors and liver lipid metabolism in rapidly aging mice

目的:研究电针对快衰老小鼠(SAMP8)肝脏中自噬相关因子LC3-Ⅱ、Beclin1、Atg7、P62表达的影响,探讨电针改善衰老小鼠肝脏脂质代谢的机制。方法:30周龄雄性SAMP8小鼠随机分为模型组、药物组、电针组,每组7只,以同周龄抗快速老化SAMR1小鼠7只作为对照组。对照组和模型组动物常规饲养4周,不进行任何干预;药物组采用雷帕霉素按(10 mg·kg^(-1)·d^(-1))腹腔注射干预(1次/日,连续每周6 d);电针组予双侧“肾俞”“太冲”穴电针治疗(15 min/次,1次/日,连续每周6 d)。检测小鼠的血清脂质代谢情况、肝脏脂质沉积情况、肝脏自噬体的分布、肝脏LC3-Ⅱ、Beclin1、Atg7、P62蛋白表达与mRNA表达的变化。结果:与对照组比较,模型组小鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)显著升高(P<0.01);模型组肝脏脂滴沉积明显,自噬体减少,自噬相关因子LC3-Ⅱ、Beclin1、Atg7蛋白及mRNA表达水平明显下降(P<0.01),P62蛋白及mRNA表达水平明显增高(P<0.01)。与模型组相比,电针组与药物组小鼠血清TG、TC、LDL含量明显降低(P<0.01);肝脏脂滴沉积减轻,自噬体增多,LC3-Ⅱ、Beclin1、Atg7的蛋白及mRNA表达水平均显著升高(P<0.01),P62蛋白及mRNA表达水平显著下降(P<0.01)。电针组肝脏Beclin1、Atg7蛋白及mRNA表达水平均与药物组无明显差异(P>0.05)。结论:电针能够减轻肝脏脂质代谢紊乱,可能与调节肝脏自噬相关因子LC3-Ⅱ、Beclin1、Atg7、P62的表达变化,从而促进SAMP8小鼠肝脏自噬有关。

Objective:To study the effects of electroacupuncture on the expressions of autophagy-related factors LC3-Ⅱ,Beclin1,Atg7,and P62 in the liver of rapidly aging(senescence accelerated mouse/prone8,SAMP8)mice,and to explore the mechanisms of electroacupuncture to improve liver lipid metabolism in mice.Methods:Thirty-week-old male SAMP8 mice were randomly divided into model group,drug group,and electroacupuncture group,with 7 mice in each group.Seven anti-rapid aging SAMR1 mice of the same age were used as the control group.The animals in the control group and the model group were bred routinely for 2 weeks without any intervention;the drug group was treated with intraperitoneal injection of rapamycin at the dose of 10 mg·kg^(-1)·d^(-1),once a day,6 consecutive days a week;the electroacupuncture group was given"Shenshu"and"Taichong"Electroacupuncture at point(15 minutes a day,6 consecutive days a week).The serum lipid metabolism and liver lipid deposition of mice were detected,the distribution of liver autophagy body,the protein and mRNA expressions of liver LC3-Ⅱ,Beclin1,Atg7 and P62 were determined.Results:Compared with the control group,the total cholesterol(TC),triglycerides(TG),and low density lipoprotein(LDL)of the model group were increased significantly(P<0.01).In the model group,lipid droplet deposition was obvious,autophagosomes were decreased,the protein and mRNA expression levels of autophagy-related factors LC3-Ⅱ,Beclin1 and Atg7 were decreased significantly(P<0.01),while the protein and mRNA expressions of P62 were increased significantly(P<0.01).Compared with the model group,the serum contents of TG,TC,and LDL of the mice in the electroacupuncture group and the drug group were decreased significantly(P<0.01),lipid droplet deposition was reduced,autophagosomes were increased,the protein and mRNA expression levels of LC3-Ⅱ,Beclin1 and Atg7 were increased significantly(P<0.01),and the protein and mRNA expression levels of P62 were decreased significantly(P<0.01).The protein and mRNA expression levels of Beclin1 and Atg7 in the liver of the electroacupuncture group were not significantly different from the drug group(P>0.05).Conclusion:Electroacupuncture can alleviate liver lipid metabolism disorders,which may be related to the regulation of the expressions of liver autophagy related factors LC3-Ⅱ,Beclin1,Atg7,and P62,thereby promoting liver autophagy in SAMP8 mice.