Objective To observe the effect of moxibustion(Moxi) at acupoints of Governor Vessel on autophagy lysosomal function and lncRNA H19 in amyloid precursor protein/presenilin 1(APP/PS1) double transgenic Alzheimer's disease(AD) mice

so as to explore its underlying mechanisms in relieving AD. Methods Fifty two male APP/PS1 double transgenic AD mice were randomly divided into model

Moxi

Moxi+inhibitor and medication(rapamycin) groups

with 13 mice in each group. Other 13 male C57 BL/6 J mice of the same age were selected as the control group. The mice of the Moxi group received aconite cake-separated Moxi stimulation at “Baihui”(GV20)

“Dazhui”(GV14) and “Fengfu”(GV16)

for 15 min

those of the Moxi+inhibitor group received intraperitoneal injection of 3-methyladenine(an inhibitor of PI3 K for suppressing autophagy) 1.5 mg· kg

(-1)

· d(-1) · d

(-1)

on the basis of Moxi

and those of the medication group received intraperitoneal injection of rapamycin 2 mg· kg(-1) on the basis of Moxi

and those of the medication group received intraperitoneal injection of rapamycin 2 mg· kg

(-1)

· d(-1) · d

(-1)

. The treatment was conducted once daily for 2 weeks. The mouse's learning-memory ability was detected by Morris water maze tests. The hippocampus tissue was sampled for observing the formation of autophagy by using transmission electron microscope

detecting the expression of Aβ_(1-42) protein with immunohistochemical staining

and for detecting the expression levels of long noncoding RNA H19(lncRNA H19)

mammalian target of rapamycin kinase(mTOR)

nuclear transcription factor EB(TFEB)

Cathepsin D and lysosome associated membrane protein-1(LAMP1) genes and proteins as well as microtubule associated protein 1 light chain 3 B(LC3 B)-Ⅱ/LC3 B-Ⅰand autophagy protein p62 protein by quantitative real-time PCR and Western blot

respectively. Results In contrast to the control group

the model group had an evident increase in the escape latency of Morris water maze test

and in the expression levels of Aβ_(1-42) protein

lncRNA H19 mRNA

mTOR mRNA and protein

and p62 protein(P

<

0.05)

and a significant decrease in the expression levels of TFEB

Cathepsin D

LAMP1 mRNAs and proteins and LC3 B-Ⅱ/LC3 B-Ⅰ(P

<

0.05). After the treatment and relevant to the model and Moxi+inhibitor groups

both the Moxi and medication groups had an obvious down-regulation in the levels of latency of Morris water maze

expression levels of Aβ_(1-42) protein

lncRNA H19 mRNA

mTOR mRNA and protein

and p62 protein(P

<

0.05)

and a significant up-regulation in the levels of TFEB

Cathepsin D

LAMP1 mRNAs and proteins and LC3 B-Ⅱ/LC3 B-Ⅰ(P

<

0.05).Conclusion Moxi at acupoints of Governor Vessel can improve cognitive function of AD mice

which may be associated with its functions in inhibiting mTOR/TFEB pathway by down-regulating the expression of lncRNA H19

improving autophagy lysosomal function

promoting autophagy and clearing away Aβ_(1-42) in the hippocampus.