OBJECTIVE To evaluate the efficacy and mechanism of Kai-Xin-San in improving intestinal function damage induced by intragastric administration of fluoxetine in chronic unpredictable mild stress (CUMS) depression model mice.

METHODS A CUMS depression mouse model was established and treated with fluoxetine (9 mg ·kg^-1·d^-1), low-dose (1.5 g ·kg^-1·d^-1) and high-dose (4.5 g ·kg^-1 ·d^-1) Kai-Xin-San, fluoxetine combined with low-dose (9 mg ·kg^-1·d^-1+1.5 g·kg^-1 ·d^-1) and high-dose (9 mg ·kg^-1 ·d^-1+4.5 g ·kg^-1 ·d^-1) Kai-Xin-San, and mosapride combined with fluoxetine (2 mg ·kg^-1 ·d^-1+9 mg ·kg^-1 ·d^-1) for 28 consecutive days. The body weight of mice was measured; the food utilization was calculated and the serum D-xylose content was measured to evaluate the intestinal mucosal absorption capacity of mice; HE staining was used to evaluate the intestinal structural damage of mice; TUNEL staining was used to evaluate the intestinal tissue apoptosis of mice; ELISA was used to detect the expression levels of brain gut peptides such as vasoactive intestinal peptide (VIP), gastrin (MTL), substance P (SP) and Ghrelin in the intestine of mice; Western blot was used to detect the expression of apoptosis signaling pathway proteins.

RESULTS Compared with the model group, fluoxetine significantly reduced the body weight of mice after 2 weeks of administration (P < 0.05); the food utilization and serum D-xylose content of mice were significantly reduced after 4 weeks of administration (P < 0.05), and the intestinal villi of depressed mice were damaged (P < 0.05) and intestinal epithelial apoptosis of mice was enhanced (P < 0.01); the expression of VIP in the small intestine of mice was upregulated (P < 0.05), and the expression of MTL, SP and Ghrelin was downregulated (P < 0.05, P < 0.01); cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 in the intestinal apoptosis signaling pathway of mice were upregulated (P < 0.05, P < 0.01). Compared with the fluoxetine group, the body weight of mice was significantly increased after 2 weeks of combined use of Kai-Xin-San and fluoxetine (P < 0.05, P < 0.01). After 4 weeks of combined use of high-dose Kai-Xin-San and fluoxetine, the food utilization and serum D-xylose expression of mice were significantly increased (P < 0.05); intestinal villus damage was improved (P < 0.05); intestinal epithelial tissue apoptosis was significantly reduced (P < 0.01); small intestinal VIP expression was significantly downregulated (P < 0.01), and the expression of MTL, SP and Ghrelin was significantly upregulated (P < 0.05); cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 in the apoptosis signaling pathway were significantly reduced (P < 0.05, P < 0.01).

CONCLUSION Kai-Xin-San has the effect of improving the gastrointestinal motility and intestinal absorption function damage caused by fluoxetine in depressed mice. Its mechanism may be related to improving the expression of brain gut peptide in the small intestine and inhibiting intestinal villi damage and intestinal tissue apoptosis.