肠激宁调控胃肠激素、AQP4和cAMP/PKA通路抗肝郁脾虚证IBS-D大鼠腹泻机制研究  

Changjining Decocion Regulates Gastrointestinal Hormones Hormones, AQPAQP4 and cAMP/PKA Pathway in IBS-D Rats of Liver-Depression and Spleen-Deficiency Syndrome Syndrome: An Anti-Diarrhea Mechanism Study

作　　者：钟毅[1] 郭红[1] 袁珍珍 ZHONG Yi;GUO Hon;YUAN Zhen-zhen(Guangdong Second Traditional Chinese Medicine Hospital,Guangzhou,Guangdong 510095;Huaihua Hospital of Traditional Chinese Medicine,Huaihua,Hunan 418000)

机构地区：[1]广东省第二中医院,广东广州510095 [2]怀化市中医院,湖南怀化418000

出　　处：《按摩与康复医学》2019年第3期42-45,共4页Chinese Manipulation and Rehabilitation Medicine

基　　金：广东省中医药管理局立项资助课题--肠激宁治疗肝气乘脾证腹泻型肠易激综合征疗效及机理研究;编号:20161016

摘　　要：目的:评价疏肝健脾、渗湿止泻中药肠激宁治疗肝郁脾虚证腹泻型肠易激综合征(IBS-D)大鼠的药效和作用机制。方法方法:将80只SPF级SD大鼠随机分为正常组、模型组、痛泻宁组(1.35g/kg)、肠激宁组(1.215g/kg)各20只,除正常组外各组大鼠均采用隔日喂食+番泻叶灌胃+强迫游泳法复制肝郁脾虚证IBS-D大鼠模型,连续灌胃给药(正常组、模型组予等容生理盐水)14天后,末次给药后1.5h测量各组大鼠体重、稀便、内脏敏感度(抬腹压力阈值和拱背压力阈值)、糖水偏好、旷场试验、小肠炭末推进率,血浆5-HT、SP、VIP及结肠PKA、cAMP、AQP4蛋白表达。结果:与模型组比较,正常组、肠激宁组和痛泻宁组大鼠体重、糖水偏好率、旷场试验活动度(垂直得分、水平得分、总得分)、内脏敏感度(抬腹压力阈值和拱背压力阈值)及结肠组织PKA、cAMP、AQP-4均有显著性增加(P<0.05),而粪便含水量、稀便级数、稀便率、小肠炭末推进率及血浆5-HT、SP、VIP均有显著性降低(P<0.05)。结论:肠激宁有可能通过抑制cAMP-PKA信号通路下调AQP4,同时下调血浆5-HT、SP、VIP以降低内脏敏感性,从而改善抑郁状态、抑制肠蠕动、减少肠道水通透性、促进对肠内容物中水的吸收,进而减少粪便含水量,抗肝郁脾虚证IBS-D大鼠的腹泻。Objective Objective: To evaluate the therapeutic effect of Changjining decoction on IBS-D rats of liver-depression and spleen-deficiency syndrome and its mechanism. Methods Methods: 80 SPF SD rats were randomly divided into control group(n=20), model group(n=20), tongxiening group(n=20, 1.35g/kg) and Changjining group(n=20, 1.215g/kg), IBS-D rats models of liver-depression and spleen-deficiency syndrome were reproduced with alternate feeding + senna leaf gavage + forced swimming except the control group, after 14 days of continuous administration(control group and model group were given isometric saline), body weight of rats, loose stools, visceral sensitivity(pressure threshold of belly lifting and arching back), sugar preference, open field test, small-intestinal carbon propulsion rate, and plasma 5-HT, SP, VIP and expression of PKA, cAMP and AQP4 protein in colon were detected at 1.5h after the last administration. Results Results: Compared with model group, body weight, sugar preference rate, activity of open field test(vertical score, horizontal score and total score), visceral sensitivity(pressure threshold of belly lifting and arching back), and PKA, cAMP and AQP4 in colonic tissue of control group, Changjining group and Tongxiening group were significantly increased(P<0.05) while fecal water content,series and rate of loose stools, small-intestinal carbon propulsion rate and plasma 5-HT, SP, VIP were significantly decreased(P<0.05). Conclusion Conclusion:Changjining decoction may cut down AQP4 by inhibiting cAMP-PKA signal pathway, and meanwhile cut down plasma 5-HT, SP and VIP to reduce visceral sensitivity, thereby to improve the depressive state, inhibit intestinal peristalsis, reduce intestinal water permeability and promote the absorption of water from intestinal contents, and then reduce the fecal water content and relieve the diarrhea in IBS-D rats of liver-depression and spleen-deficiency syndrome.

关 键 词：腹泻型肠易激综合征(IBS-D) 肝郁脾虚证 肠激宁 胃肠激素 水通道蛋白 cAMP/PKA信号通路 

分 类 号：R285.5[医药卫生—中药学]