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 Depression Model Mice

作　　者：李鑫 李璇 黄小宁 黄灵欣 伍嘉慧 董婷霞[2] 詹华强[2] 段金廒[1] 朱悦[1] LI Xin;LI Xuan;HUANG Xiaoning;HUANG Lingxin;WU Jiahui;DONG Tingxia;TSIM Wah Keung;DUAN Jin’ao;ZHU Yue(School of Pharmacy,Jiangsu Key Laboratory for Research of TCM Formulae,Jiangsu Key Laboratory for High Technology Research of TCM Formulae,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing University of Chinese Medicine,Nanjing 210023,China;Chinese Medicine Research and Development Center of Life Science Division,The Hong Kong University of Science and Technology,Hongkong 999077,China)

机构地区：[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 [2]香港科技大学生命科学部中药研发中心,中国香港999077

出　　处：《南京中医药大学学报》2025年第3期313-322,共10页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家重点研发计划战略性科技创新合作项目(2022YFE0201700);国家自然科学基金面上项目(82374167,81973591)。

摘　　要：目的评价开心散改善慢性压力应激(CUMS)抑郁模型小鼠灌胃氟西汀导致的肠道功能损伤的效用及机制。方法构建CUMS抑郁小鼠模型,分别给予氟西汀(9 mg·kg^(-1)·d^(-1))、开心散低剂量(1.5 g·kg^(-1)·d^(-1))与高剂量(4.5 g·kg^(-1)·d^(-1)),氟西汀合用开心散低剂量(9 mg·kg^(-1)·d^(-1)+1.5 g·kg^(-1)·d^(-1))与高剂量(9 mg·kg^(-1)·d^(-1)+4.5 g·kg^(-1)·d^(-1)),莫沙必利合用氟西汀(2 mg·kg^(-1)·d^(-1)+9 mg·kg^(-1)·d^(-1)),连续给药28 d。测量小鼠体质量;计算小鼠食物利用度、测量血清D-木糖含量评价小鼠肠黏膜吸收能力;采用HE染色法评价小鼠肠道结构损伤;采用TUNEL染色法评价小鼠肠道组织凋亡情况;采用ELISA法检测小鼠肠道中血管活性肠肽(Vasoactive intestinal peptide,VIP)、胃泌素(Motilin,MTL)、P物质(Substance P,SP)与饥饿素(Ghrelin)等脑肠肽的水平;采用Western blot法检测凋亡信号通路蛋白表达。结果与模型组相比,氟西汀给药2周后显著降低小鼠体质量(P<0.05);给药4周后小鼠的食物利用度与血清D-木糖含量显著降低(P<0.05),同时损伤抑郁小鼠肠道绒毛(P<0.05)并增强小鼠肠上皮凋亡(P<0.01);上调小鼠小肠中VIP表达(P<0.05),下调MTL、SP与Ghrelin表达(P<0.05,P<0.01);上调小鼠肠道凋亡信号通路中cleaved Caspase-3/Caspase-3、cleaved Caspase-9/Caspase-9(P<0.05,P<0.01)。与氟西汀组比较,开心散与氟西汀合用2周后,可显著提高小鼠体质量(P<0.05,P<0.01);高剂量开心散与氟西汀合用4周后,小鼠食物利用度与血清D-木糖表达显著提高(P<0.05);肠道绒毛损伤得到改善(P<0.05);肠上皮组织凋亡显著降低(P<0.01);小肠VIP表达显著下调(P<0.01),MTL、SP与Ghrelin的表达显著上调(P<0.05);凋亡信号通路中cleaved Caspase-3/Caspase-3、cleaved Caspase-9/Caspase-9显著降低(P<0.05,P<0.01)。结论开心散具有改善抑郁小鼠氟西汀导致的胃肠道动力与肠道吸收功能损伤的效用,其机制可能与改善�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 com

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 

分 类 号：R285.5[医药卫生—中药学]