电针联合高强度间歇训练对阿尔兹海默病模型大鼠TREM2信号通路的影响

Electroacupuncture combined with high-intensity interval training can improve cognition for persons with Alzheimer′s disease

目的探讨电针和高强度间歇训练(HIIT)联合治疗阿尔兹海默病(AD)模型大鼠的作用机制。方法将大鼠随机分为正常组、模型组、电针组、HIIT组、联合组(电针+HIIT组)。除正常组外,其余各组采用120 mg/(kg·d)D-半乳糖皮下注射和100 mg/(kg·d)无水AlCl_(3)腹腔注射进行AD模型大鼠造模。于造模成功后第2天开始干预,电针组和联合组采用0.25 mm×13 mm不锈钢针灸针平刺百会穴、直刺肾俞穴,深度2~3 mm,接电针仪强度1.0 mA,2.0 Hz疏密波,20 min/日,每周治疗5 d,连续3周;HIIT组和联合组均采用HIIT运动方案进行训练,每日训练50 min,每周训练5 d,为期3周;正常组和模型组不行任何干预。分别于造模第4周后和干预3周后,观察大鼠一般情况,并采用水迷宫实验和旷场实验观察大鼠行为学变化。HE染色观察海马区组织形态变化,ELISA检测血清中的超氧化物歧化酶(SOD)、丙二醛(MDA)、胆碱乙酰基转位酶神经元(chAT)、乙酰胆碱酯酶(AchE)含量;用RT-PCR法检测大鼠海马髓细胞触发受体2(TREM2)信号通路相关基因表达。结果干预后,与正常组相比,模型组、电针组、HIIT组和联合组认知功能降低、海马区组织病理形态改变、血清中SOD、chAT水平和海马中TREM2 mRNA、DAP12 mRNA水平均明显降低,血清中MDA、AchE含量和海马中的ERK1 mRNA和ERK2 mRNA水平均明显增加(P<0.05);与模型组比较,除HIIT组的平台穿梭次数和血清中DAP12 mRNA水平差异无统计学意义(P>0.05)外,电针组、HIIT组和联合组的其余行为学指标均明显改善,且血清中的SOD、chAT和海马中TREM2 mRNA水平均明显增加,血清中的MDA、AchE和海马中的ERK1 mRNA、ERK2 mRNA水平均明显降低(P<0.05),电针组和联合组DAP12 mRNA水平显著提高(P<0.05);与联合组比较,电针组和HIIT组认知功能降低、海马区组织病理形态改变、血清中的SOD和chAT及海马中的TREM2 mRNA和DAP12 mRNA水平均明显降低,血清中的MDA和AchE及海马中的ERK1 mRNA、ERK2 mRNA水平均明显增加(P<0.05)。结论电针联合HIIT可能通过激活TREM2通路来促进大鼠抗氧化能力,改善AD大鼠的认知功能。

Objective To explore any effect of treating rats modeling Alzheimer′s disease(AD)using elec-troacupuncture combined with high intensity interval training(HIIT)and the mechanism underlying any effect observed.Methods Rats were randomly divided into a normal group,a model group,an electroacupuncture group,an HIIT group and a combined(electroacupuncture+HIIT)group.All of the rats except those in the normal group were injec-ted with 120mg/kg of D-galactose subcutaneously and 100mg/kg of anhydrous AlCl_(3)intraperitoneally to induce a model of AD.On the 2nd day after the successful modeling,in the electroacupuncture and combined groups,0.25mm×13mm stainless steel acupuncture needles were used to puncture the Baihui and Shenshu points to a depth of 2 to 3mm while 1.0mA of 2.0Hz electrical stimulation was applied for 20min/day.The HIIT and combined groups underwent 50 minutes of HIIT training daily,5 days a week for 3 consecutive weeks.Four weeks after the modeling and 3 weeks after the in-tervention,the rats′general condition was observed,and water maze and open field experiments were conducted.Any morphological changes in the hippocampus were measured using hematoxylin and eosin staining,and the rats′serum lev-els of superoxide dismutase(SOD),malondialdehyde(MDA),choline acetyl translocase(chAT)and acetylcholine esterase(AchE)were detected using enzyme-linked immunosorbent assays.The gene expression of the trigger receptor expressed on myeloid cells 2(TREM2)signaling pathway in the myeloid cells of the hippocampus was detected using reverse-transcription polymerse chain reactions.Results After the intervention,significant cognitive impairment was observed in all except the normal group,accompanied by a significant decrease in the serum levels of SOD and chAT.The mRNA levels of TREM2 and DAP12 in the hippocampus were also lower,accompanied by significant increases in serum MDA and AchE and in ERK1 mRNA and ERK2 mRNA in the hippocampus.Compared with model group,signif-icant improvement was observed in the electroacupuncture,HIIT and combined groups after the treatments in all of the outcomes except platform shuttle times and serum DAP12 mRNA levels in HIIT group.They had a significant increase in average serum SOD and chAT,and in the average TREM2 mRNA levels in the hippocampus,and significant decrea-ses in their average serum MDA and AchE,and in the ERK1 mRNA and ERK2 mRNA levels in the hippocampus.After the intervention,the average DAP12 mRNA levels of the electroacupuncture and combined groups had increased signifi-cantly.Compared with the combined group,the cognitive function,SOD and chAT in serum,TREM2 mRNA and DAP12 mRNA in the hippocampus had decreased significantly in the electroacupuncture and HIIT groups,with signifi-cant histomorphology changes in the HIIT group,while MDA and AchE in serum and ERK1 mRNA and ERK2 mRNA levels in hippocampus had increased significantly.Conclusion Combining electroacupuncture with HIIT may promote antioxidant capacity and cognitive function through activating the TREM2 pathway,at least in rats modeling AD.