基于SCF/c-Kit通路探讨加味安肠汤联合阿洛司琼对腹泻型肠易激综合征大鼠的作用机制OA
Mechanisms of Modified Anchang Decoction Combined with Alosetron on Diarrhea-Predominant Irritable Bowel Syndrome in Rats Based on SCF/c-Kit Pathway
目的 基于干细胞因子(Stem cell factor,SCF)/细胞源性酪氨酸激酶受体通路(cellular tyrosine kinase receptor pathway,c-Kit)探讨加味安肠汤联合阿洛司琼对腹泻型肠易激综合征大鼠的作用机制.方法 将100只同月龄SPF级Wistar大鼠,随机选取80只大鼠进行造模,制备腹泻型肠易激综合征大鼠模型,造模成功后采用随机数字表法将大鼠分为模型组(给予10 ml/kg生理盐水灌胃)、阿洛司琼组(给予1.008 mg/kg阿洛司琼灌胃)、加味安肠汤组(给予18.9 g/kg加味安肠汤灌胃)、中西医结合组(给予1.008 mg/kg阿洛司琼联合18.9 g/kg加味安肠汤灌胃),每组20只,剩余20只大鼠设为空白组.末次治疗后8 h,将各组大鼠麻醉(10%水合氯醛)后处死,取腹主动脉血10 ml及收集结肠组织,观察各组大鼠一般情况、5-羟色胺(5-hydroxytryptamine,5-HT)、SCF水平;免疫荧光法测定各组大鼠c-Kit阳性卡哈尔间质细胞(Interstitial cells of cajal,ICC)水平及Western blot测定各组大鼠SCF、c-Kit蛋白水平.结果 与空白组比较,模型组体质量、SCF水平、ICC荧光强度、c-Kit蛋白水平明显降低,5-HT水平明显升高,差异有统计学意义(P<0.05),表示造模成功,且造模后大鼠SCF水平、ICC荧光强度、c-Kit蛋白水平呈异常升高,5-HT水平呈异常下降;治疗1、2周后,与模型组比较,阿洛司琼组、加味安肠汤组、中西医结合组体质量明显升高,差异有统计学意义(P<0.05);与阿洛司琼组和加味安肠汤组比较,中西医结合组体质量明显升高,差异有统计学意义(P<0.05).与模型组比较,阿洛司琼组、加味安肠汤组、中西医结合组5-HT水平下降,SCF水平、ICC荧光强度、SCF、c-Kit蛋白水平升高,差异有统计学意义(P<0.05);与阿洛司琼组和加味安肠汤组比较,中西医结合组5-HT水平明显下降,SCF水平、ICC荧光强度、c-Kit蛋白水平升高,差异有统计学意义(P<0.05).结论 加味安肠汤联合阿洛司琼可通过SCF/c-Kit通路发挥治疗腹泻型肠易激综合征的作用.
Objective To investigate the mechanisms of action of modified Anchang Decoction combined with alosetron in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on the stem cell factor(SCF)/cellular tyrosine kinase receptor(c-Kit)signaling pathway.Methods A total of 100 SPF Wistar rats of the same age were used,of which 80 rats were randomly selected for modeling to establish an IBS-D rat model.After successful modeling,the rats were randomly divided,using a random number table,into a model group(intragastric administration of 10 ml/kg normal saline),an alosetron group(intragastric administration of 1.008 mg/kg),a modified Anchang Decoction group(intragastric administration of 18.9 g/kg modified Anchang Decoction),and an integrated traditional Chinese and Western medicine group(intragastric administration of 1.008 mg/kg alosetron combined with 18.9 g/kg modified Anchang Decoction),with 20 rats in each group.The remaining 20 rats served as the blank control group.Eight hours after the final treatment,rats in each group were anesthetized with 10%chloral hydrate,sacrificed,and 10 ml of abdominal aortic blood and colon tissues were collected.The general conditions of the rats,as well as levels of 5-Hydroxytryptamine(5-HT)and SCF,were observed.Immunofluorescence was used to determine the levels of c-Kit-positive interstitial cells of Cajal(ICC),and Western blot analysis was used to measure SCF and c-Kit protein expression in each group.Results Compared with the blank group,the model group showed significantly reduced body weight,SCF levels,ICC fluorescence intensity,and SCF and c-Kit protein expression,while 5-HT levels were significantly increased(P<0.05),indicating successful model establishment.After modeling,SCF levels,ICC fluorescence intensity,and SCF and c-Kit protein expression showed abnormal increases,while 5-HT levels showed abnormal decreases.After 1 and 2 weeks of treatment,body weight in the alosetron group,modified Anchang Decoction group,and integrated traditional Chinese and Western medicine group was significantly increased compared with the model group(P<0.05).Compared with the alosetron group and modified Anchang Decoction group,body weight in the integrated traditional Chinese and Western medicine group was significantly increased(P<0.05).Compared with the model group,5-HT levels were decreased,while SCF levels,ICC fluorescence intensity,and SCF and c-Kit protein expression were increased in the alosetron group,modified Anchang Decoction group,and integrated treatment group(P<0.05).Compared with the alosetron group and modified Anchang Decoction group,the integrated traditional Chinese and Western medicine group showed significantly lower 5-HT levels and higher SCF levels,ICC fluorescence intensity,and SCF and c-Kit protein expression(P<0.05).Conclusion Modified Anchang Decoction combined with alosetron exerts therapeutic effects on IBS-D through the SCF/c-Kit signaling pathway.
袁小晶;王凡
陕西省延安市中医医院,陕西 延安 716000延安大学附属医院,陕西 延安 716001
医药卫生
SCF/c-Kit通路加味安肠汤阿洛司琼腹泻型肠易激综合征
SCF/c-Kit pathwayModified Anchang Decoctionalosetrondiarrhea-predominant irritable bowel syndrome
《世界中西医结合杂志》 2026 (1)
53-59,7
第六批全国老中医药专家学术经验继承工作项目(国中医药人教发[2018]29号)
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