Evaluation of the Efficacy of Kai-Xin-San Combined with Fluoxetine in Improving Intestinal Absorption Damage in Depres-sion Model Mice
10.14148/j.issn.1672-0482.2025.0313
- VernacularTitle:开心散联合氟西汀改善抑郁模型小鼠肠道吸收功能损伤的效用评价研究
- Author:
Xin LI
1
;
Xuan LI
;
Xiaoning HUANG
;
Lingxin HUANG
;
Jiahui WU
;
Tingxia DONG
;
TSIM Wah KEUNG
;
Jin'ao DUAN
;
Yue ZHU
Author Information
1. 南京中医药大学药学院,江苏省方剂研究重点实验室/江苏省方剂高技术研究重点实验室/中药资源产业化与方剂创新药物国家地方联合工程研究中心/江苏省中药资源产业化过程协同创新中心,江苏 南京 210023
- Publication Type:Journal Article
- Keywords:
Kai-Xin-San;
fluoxetine;
depression;
gastrointestinal motility;
intestinal absorption;
brain gut peptide;
apoptosis
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2025;41(3):313-322
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To evaluate the efficacy and mechanism of Kai-Xin-San in improving intestinal function damage in-duced 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 dam-age of mice;TUNEL staining was used to evaluate the intestinal tissue apoptosis of mice;ELISA was used to detect the expression lev-els 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 ser-um 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 upregulat-ed(P<0.05,P<0.01).Compared with the fluoxetine group,the body weight of mice was significantly increased after 2 weeks of com-bined 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 fluoxe-tine,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 dam-age 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.
