健脾理气方抑制肥大细胞改善十二指肠紧密连接蛋白表达治疗功能性消化不良的机制研究  

Mechanism of Jianpi Liqi Decoction in treatment of functional dyspepsia by inhibiting mast cell activation and improving the expression of tight junction proteins

作　　者：常雄飞 沈凌宇 张立宏 谭海成 CHANG Xiongfei;SHEN Lingyu;ZHANG Lihong;TAN Haicheng(Department of Gastroenterology,Shunyi Hospital of Traditional Chinese Medicine,Beijing 101300,China)

机构地区：[1]北京中医医院顺义医院脾胃科,北京101300

出　　处：《上海中医药杂志》2021年第11期91-96,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82004270);北京市属医院科研培育计划项目(PZ2020024);北京中医医院顺义医院院级课题(SYYJ-201803)。

摘　　要：目的探索健脾理气方通过抑制十二指肠肥大细胞(MC)脱颗粒、改善十二指肠紧密连接蛋白(TJs)表达、恢复肠道屏障功能,治疗功能性消化不良(FD)的机制。方法6周龄SPF级SD雄性大鼠24只,随机分为对照组、模型组、中药组及拮抗剂组,每组6只。除对照组外,其余各组大鼠采用夹尾应激方法建立FD模型。造模结束后,对照组及模型组予纯净水灌胃,中药组予健脾理气方水煎剂灌胃,拮抗剂组予促肾上腺皮质激素释放激素(CRH)拮抗剂腹腔注射。干预结束后取十二指肠,采用Western blot法测定局部CRH主要受体1(CRHR1)、MC标记性蛋白类胰蛋白酶(Tryptase)及蛋白酶激活受体2(PAR-2)、肌球蛋白轻链激酶(MLCK)及TJs(JAM-A、ZO-1、claudin-1)表达情况。结果与对照组比较,模型组大鼠十二指肠CRHR1、Tryptase、PAR-2、MLCK表达量显著升高(P<0.05),而TJs(JAM-A、ZO-1、claudin-1)表达下调(P<0.05)。与模型组比较,中药组及拮抗剂组大鼠CRHR1、Tryptase、PAR-2、MLCK表达下调(P<0.05),同时TJs(JAM-A、ZO-1、claudin-1)表达量显著升高(P<0.05)。结论CRH介导的MC激活,释放炎症介质,下调十二指肠局部TJs表达,导致屏障受损可能是FD发病机制之一,而健脾理气方可能通过抑制该损伤性通路,恢复十二指肠局部屏障功能,对FD起到治疗作用。Objective To explore the mechanism of Jianpi Liqi Decoction in the treatment of functional dyspepsia(FD)by inhibiting degranulation of duodenal mast cells(MC),improving the expression of duodenal tight junction proteins(TJs)and restoring intestinal barrier function.Methods Twenty-four 6-week-old SPF male SD rats were randomly divided into control group,model group,traditional Chinese medicine treatment group and CRH antagonist group,6 rats in each grpup.Except for the control group,the FD model was established by tail clamping stress in other groups.After the establishment of the model,the control group and the model group were given pure water gavage,the traditional Chinese medicine treatment group given Jianpi Liqi Decoction gavage and the CRH antagonist group injected with antagonist intraperitoneally.After the intervention,the duodenum was taken and the expressions of corticotropin releasing hormone(CRH)major receptor 1(CRHR1),MC marker protein trypsin(Tryptase),protease activated receptor 2(PAR-2),myosin light chain kinase(MLCK),and TJs(JAM-A,ZO-1,claudin-1)in the duodenum were determined by Western blot.Results Compared with the control group,the expressions of CRHR1,Tryptase,PAR-2,MLCK in the duodenum of the model group were significant increased(P<0.05),while the expressions of TJs(JAM-A,ZO-1,claudin-1)were down-regulated(P<0.05).Compared with the model group,the expressions of CRHR1,Tryptase,PAR-2 and MLCK in the traditional Chinese medicine group and CRH antagonist group were down-regulated,while the expression of TJs(JAM-A,ZO-1,claudin-1)was significantly increased.Conclusion CRH-mediated activation of MC,release of inflammatory mediators and down-regulation of local TJs expression in the duodenum resulting in barrier damage may be one of the pathogenesis of FD,and Jianpi Liqi Decoction may inhibit the injury pathway,restore the function of local duodenal barrier and play a therapeutic role in FD.

关 键 词：功能性消化不良 健脾理气方 十二指肠 促肾上腺皮质激素释放激素 肥大细胞 紧密连接蛋白 肠道屏障 中药研究 

分 类 号：R285.5[医药卫生—中药学]