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基于“脾主运化”理论探讨芪药鸡金粥通过PI3K/Akt/NF-κB通路防治化疗致胃肠黏膜损伤的机制

Mechanism of prevention and treatment of chemotherapy-induced gastrointestinal mucosal injury with Qi-Yao-Ji porridge via PI3K/Akt/NF-κB pathway based on the theory of“the spleen governs the transport and transformation”
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摘要 目的探讨“脾主运化”理论在芪药鸡金粥防治化疗致胃肠黏膜损伤的指导意义及其作用机制。方法48只雄性SD大鼠常规适应性喂养7 d后,随机分为空白组、模型组、药膳组,每组16只。药膳组于实验第1天开始给予芪药鸡金粥灌胃,模型组及空白组给予白粥灌胃,均1次/d,每次10 mL/(kg·d),连续14 d。实验第7天,各组灌胃30 min后,药膳组和模型组大鼠给予氟尿嘧啶注射液150 mg/kg一次性腹腔注射,空白组给予等量生理盐水注射。分别于实验第8天和实验第15天每组各取8只大鼠处死,HE染色观察回肠组织病理形态,Western blot法检测回肠组织中封闭蛋白-1(Claudin-1)、闭锁蛋白(Occludin)、结合黏附分子-1(JAM-1)、闭锁小带蛋白(ZO-1)、磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(Akt)、IκBα、p-Akt、p-PI3K蛋白表达情况。结果实验第8天和第15天,模型组和药膳组大鼠回肠组织中Claudin-1、Occludin、JAM-1、ZO-1、PI3K、p-PI3K、Akt、p-Akt、IκBα蛋白相对表达量均明显低于同期空白组(P均<0.05),但药膳组Claudin-1、Occludin、JAM-1、ZO-1、PI3K、p-PI3K、Akt、p-Akt、IκBα蛋白相对表达量均明显高于同期模型组(P均<0.05)。结论基于“脾主运化”理论的芪药鸡金粥可调节化疗大鼠肠道紧密连接蛋白的表达,保护肠道机械屏障的结构与功能,机制可能与抑制PI3K/Akt/NF-κB信号通路激活相关。 Objective It is to explore the guiding significance of the theory of“spleen governing transport and transformation”in the prevention and treatment of chemotherapy-induced gastrointestinal mucosal damage with Qi-Yao-Ji porridge and its mechanism of action.Methods After 7 days of routine adaptive feeding,48 male SD rats were randomly divided into blank group,model group,medicated diet group,with 16 rats in each group.The medicinal diet group was given Qi-Yao-Ji porridge by gavage,and the model group and blank group were given white porridge by gavage from the 1st day of the experiment,all once daily,10 mL/(kg·d)per day,continuously treated for 14 days.On the 7 th day of the experiment,after 30 min of gavage in each group,the rats of the medicated diet group and model group were given 5-FU 150 mg/kg by one-time intraperitoneal injection for modeling,the blank group was injected with the same amount of normal saline.8 rats were taken from each group and executed on day 8 and day 15 of the experiment,respectively.HE staining was performed to observe the pathological morphology of ileal tissues,and Western blot method was used to detect the expressions of Claudin-1,Occludin,junctional adhesion molecule-1(JAM-1),zonulaoccludens-1(ZO-1),phosphatidylinositol-3-kinase(PI3K),protein kinase B(Akt),IκBα,p-Akt,and p-PI3K proteins in the ileal tissues.Results On the 8 th and 15 th days of the experiment,the relative expressions of Claudin-1,Occludin,JAM-1,ZO-1,PI3K,p-PI3K,Akt,p-Akt,and IκBαproteins in the ileal tissues of rats in the model group and the medicated diet group were significantly lower than those in the blank group during the same time period(all P<0.05),but the relative expressions of Claudin-1,Occludin,JAM-1,ZO-1,PI3K,p-PI3K,Akt,p-Akt,and IκBαproteins were significantly higher in the medicinal diet group than those in the model group during the same period(all P<0.05).Conclusion Qi-Yao-Ji porridge made based on the theory of“spleen governs transportation and transformation”can regulate the expression of tight junction proteins in the intestinal mechanical barrier of rats treated with chemotherapy,thereby protecting the structure and function of mechanical barrier,the mechanism may be closely related to inhibiting the activation of PI3K/AKT/NF-κB signaling pathway.
作者 翁美华 邓丽金 胡静温 周红娟 陈锦秀 陈焰南 WENG Meihua;DENG Lijin;HU Jingwen;ZHOU Hongjuan;CHEN Jinxiu;CHEN Yannan(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China;Zhongshan Hospital Affiliated to Xiamen University,Xiamen 361000,Fujian,China;West China Hospital of Sichuan University,Chengdu 610000,Sichuan,China)
出处 《现代中西医结合杂志》 CAS 2023年第18期2519-2524,2594,共7页 Modern Journal of Integrated Traditional Chinese and Western Medicine
基金 福建省自然科学基金项目(2020J01131813)。
关键词 脾主运化 芪药鸡金粥 胃肠黏膜损伤 紧密连接蛋白 磷脂酰肌醇-3-激酶 蛋白激酶B spleen governs transportation and transformation Qi-Yao-Ji porridge gastrointestinal mucosal injury tight junction protein phosphatidylinositol-3-kinase phosphatidylinositol-3-kinase
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