Objective: To explore the mechanism of Fuzi Lizhongtang in warming Yang

invigorating the spleen and dispelling dampness through AQP4-ANP-pGC pathway. Method: A total of 120 clean grade Wistar rats were randomly selected and divided into blank control group

sham operation group

model group

and high

middle

low-dose Fuzi Lizhongtang groups

with 20 rats in each group.The blank control group was fed normally.Animal models were established in the sham operation group and the model group through interscapular brown adipose tissue (BAT) resection+high-fat diet+cold environment stimulation at alternate days (the sham operation group only received BAT without resection).The high-fat diet was fed for 30 days since the first day of the operation.In addition to the treatment for the model group

the three Fuzi Lizhongtang groups were respectively treated with high-dose (40 g · kg-1 · d-1)

middle-dose (20 g · kg-1 · d-1) and low-dose (10 g · kg-1 · d-1) Fuzi Lizhongtang

while the other groups were given the same amount of normal saline.Materials were collected after 30 days of administration

(the model group was collected on the first day after successful modeling).The morphologic changes in gastric antrum and ileum in rats were observed by HE staining; ANP content was detected by ELISA; the mRNA expression of AQP4 was detected by Real-time PCR.And the AQP4 content was detected by Western blot. Result: HE staining of gastric antrum and ileum in rats was observed under light microscope.Pathological changes in gastrointestinal tissues in rats in each Fuzi Lizhongtang group were alleviated to different degrees

with the best effect in high-dose group.Compared with the control group and the sham operation group

the contents of AQP4

ANP and the relative expression of AQP4 mRNA in the model group decreased (P<0.05

P<0.01).Compared with the model group

the contents of AQP4

ANP and the relative expression of AQP4 mRNA in the middle and the high dose groups increased (P<0.05

P<0.01). Conclusion: Fuzi Lizhongtang may regulate body fluid metabolism in rats with spleen Yang deficiency syndrome by changing the contents of AQP4

ANP and the expression of AQP4 mRNA in AQP4-ANP-pGC pathway.