南京中医药大学学报2025，Vol.41Issue(3)：313-322,10.DOI:10.14148/j.issn.1672-0482.2025.0313
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
Evaluation of the Efficacy of Kai-Xin-San Combined with Fluoxetine in Improving Intestinal Absorption Damage in Depres-sion Model Mice
摘要
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.关键词
开心散/氟西汀/抑郁症/胃肠道动力/肠道吸收/脑肠肽/凋亡Key words
Kai-Xin-San/fluoxetine/depression/gastrointestinal motility/intestinal absorption/brain gut peptide/apoptosis分类
医药卫生引用本文复制引用
李鑫,李璇,黄小宁,黄灵欣,伍嘉慧,董婷霞,詹华强,段金廒,朱悦..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[J].南京中医药大学学报,2025,41(3):313-322,10.基金项目
国家重点研发计划战略性科技创新合作项目(2022YFE0201700) （2022YFE0201700）
国家自然科学基金面上项目(82374167,81973591) （82374167,81973591）
