戊己丸对炎症后肠易激综合征大鼠脑肠肽的调控作用
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摘要
目的寻找诊断和治疗肠易激综合征(IBS)的生物学指标。方法采用乙酸加束缚应激法建立炎症后肠易激综合征(PI-IBS)动物模型;采用大鼠结肠运动指数(MI)、2 h内排出的粪粒数以及玻璃小球排出时间评价大鼠结肠的运动能力;观察PI-IBS模型大鼠的形成以及戊己丸对其的治疗作用;采用ELISA法检测PI-IBS大鼠脑和结肠组织中的降钙素基因相关肽(CGRP)、胃动素(MTL)、神经肽Y(NPY)、P物质(SP)、生长抑素(SS)、血管活性肠肽(VIP)、胆囊收缩素(CCK)水平。结果成功建立PI-IBS大鼠模型。模型大鼠体重降低;摄食量减少;排便量增多;出现稀便和无定形软便;自主运动量减少;结肠MI显著增加(P<0.05);大鼠排出的粪粒数显著增加(P<0.05);玻璃小球排出时间显著缩短(P<0.05)。戊己丸治疗7 d后能够明显改善以上症状。与正常对照组相比,PI-IBS大鼠脑组织中的CGRP、SS和VIP水平显著增加(P<0.05),NPY浓度显著降低(P<0.05);而戊己丸给药可以显著降低CGRP、SS和VIP浓度水平(P<0.05),显著升高NPY浓度水平(P<0.05)。与正常对照组相比,PI-IBS大鼠结肠组织中的CCK、NPY、MTL、SS和VIP均显著降低(P<0.05);戊己丸给药能够显著升高CCK和VIP水平(P<0.05)。结论戊己丸可通过调节IBS大鼠脑和结肠组织内多种脑肠肽的水平用来治疗IBS,这些可被调节的异常变化的脑肠肽可以成为潜在的诊断和治疗IBS的生物学指标。
Objective To explore the biological indicators of diagnosis and treatment of irritable bowel syndrome( IBS),and to explore the mechanism of action of a Chinese medicine Wuji Pill( WJW) on irritable bowel syndrome( IBS). Methods( 1) Postinflammatory irritable bowel syndrome( PI-IBS) rat model was established by acetic acid plus restraint stress method.( 2) The colonic motor ability of rats was evaluated by colon motility index( MI),the number offecal particles discharged within 2 h,and the time of glass pellet discharge.( 3) The formation of PI-IBS model rats and the therapeutic effect of WJW were observed.( 4) The levels of calcitonin gene-related peptide( CGRP),motilin( MTL),neuropeptide Y( NPY),substance P( SP),somatostatin( SS),vasoactive intestinal peptide( VIP),and cholecystokinin( CCK) in the brain and colon tissues of PI-IBS rats were measured by ELISA. Results( 1) The rat PI-IBS model was successfully established. Compared with the normal group,the body weight of the model rats was decreased,the food intake decreased,the amount of feces increased, loose stools and amorphous soft stools appeared, voluntary movements decreased,colon motility index( MI) significantly increased( P < 0. 05),the number of fecal particles discharged significantly increased( P < 0. 05),and the glass pellet discharge time was significantly shortened( P < 0. 05).( 2)WJW treatment for 7 days significantly improved a variety of symptoms. Compared with the normal control,the levels of CGRP,SS and VIP in the brain tissue of PI-IBS rats were significantly increased( P < 0. 05),and the NPY concentration was significantly decreased( P < 0. 05). However,the treatment with WJW significantly reduced CGRP,SS and VIP levels( P < 0. 05),and significantly increased the NPY concentration level( P < 0. 05).( 3) Compared with the normal control group,the levels of CCK,NPY,MTL,SS and VIP in colonic tissues of PI-IBS rats were significantly decreased( P< 0. 05),while WJW significantly increased the CCK and VIP levels. Conclusions WJW can be used to treat IBS by regulating the levels of various brain-gut peptides in the brain and colon tissues of IBS rats. These anomalous and adjustable brain-gut peptides may become a potential biomarker for the diagnosis and treatment of IBS.
Objective To explore the biological indicators of diagnosis and treatment of irritable bowel syndrome( IBS),and to explore the mechanism of action of a Chinese medicine Wuji Pill( WJW) on irritable bowel syndrome( IBS). Methods( 1) Postinflammatory irritable bowel syndrome( PI-IBS) rat model was established by acetic acid plus restraint stress method.( 2) The colonic motor ability of rats was evaluated by colon motility index( MI),the number offecal particles discharged within 2 h,and the time of glass pellet discharge.( 3) The formation of PI-IBS model rats and the therapeutic effect of WJW were observed.( 4) The levels of calcitonin gene-related peptide( CGRP),motilin( MTL),neuropeptide Y( NPY),substance P( SP),somatostatin( SS),vasoactive intestinal peptide( VIP),and cholecystokinin( CCK) in the brain and colon tissues of PI-IBS rats were measured by ELISA. Results( 1) The rat PI-IBS model was successfully established. Compared with the normal group,the body weight of the model rats was decreased,the food intake decreased,the amount of feces increased, loose stools and amorphous soft stools appeared, voluntary movements decreased,colon motility index( MI) significantly increased( P < 0. 05),the number of fecal particles discharged significantly increased( P < 0. 05),and the glass pellet discharge time was significantly shortened( P < 0. 05).( 2)WJW treatment for 7 days significantly improved a variety of symptoms. Compared with the normal control,the levels of CGRP,SS and VIP in the brain tissue of PI-IBS rats were significantly increased( P < 0. 05),and the NPY concentration was significantly decreased( P < 0. 05). However,the treatment with WJW significantly reduced CGRP,SS and VIP levels( P < 0. 05),and significantly increased the NPY concentration level( P < 0. 05).( 3) Compared with the normal control group,the levels of CCK,NPY,MTL,SS and VIP in colonic tissues of PI-IBS rats were significantly decreased( P< 0. 05),while WJW significantly increased the CCK and VIP levels. Conclusions WJW can be used to treat IBS by regulating the levels of various brain-gut peptides in the brain and colon tissues of IBS rats. These anomalous and adjustable brain-gut peptides may become a potential biomarker for the diagnosis and treatment of IBS.
引文
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[9]Keszthelyi D,Troost FJ,Jonkers DM,et al.Alterations in mucosal neuropeptides in patients with irritable bowel syndrome and ulcerative colitis in remission:A role in pain symptom generation?[J].Eur J Pain,2013,17(9):1299-1306.
[10]肖小芹,舒圆月,邓桂明,等.乌药水提液对腹泻型肠易激综合征模型大鼠Ghrelin、MTL、SP、Sec水平的影响[J].湖南中医药大学学报,2017,37(05):477-480.Xiao XQ,Shu YY,Deng GM,et al.Effect of water extract of Lindera Aggregata on Ghrelin,MTL,SP and Sec levels in rats with diarrhea-predominant irritable bowel syndrome[J].J Hunan Univ Chin Med,2017,37(05):477-480.
[11]Bravo JA,Dinan TG,Cryan JF.Alterations in the central CRF system of two different rat models of comorbid depression and functional gastrointestinal disorders[J].Int J Neuropsychopharmacol,2011,14(5):666-683.
[12]Kiank C,TachéY,Larauche M.Stress-related modulation of inflammation in experimental models of bowel disease and postinfectious irritable bowel syndrome:role of corticotropin releasing factor receptors[J].Brain Behav Immunity,2010,24(1):41-48.
[2]周福生,程宏辉,祝淑贞.心胃相关理论及临床应用[J].浙江中医学院学报,2004,28(2):7-8.Zhou FS,Cheng HH,Zhu SZ.Clinical application of the heartstomach relativity theory[J].J Zhejiang Chin Med Univ,2004,28(2):7-8.
[3]王旭丹.从脑肠轴探讨痞满肝胃不和证机制[J].世界中西医结合杂志,2009,4(8):588-589.Wang XD.Study on the mechanism of disharmony of liver and stomach via brain-gut axis[J].World J Int Trad Wes Med,2009,4(8):588-589.
[4]Chen Y,Xiao SM,Gong ZP,et al.Wuji Wan Formula ameliorates diarrhea and disordered colonic motility in post inflammation irritable bowel syndrome rats via modulating the gut microbiota and enhancing barrier function[J].Front Microbiol,2017,23(8):2307-2319.
[5]张璐,周鸿,吕宾,等.CRF在大鼠5-HT信号通路和内脏高敏感中的作用[J].胃肠病学,2011,09:534-538.Zhang L,Zhou H,Lyu B,et al.Role of CRF on 5-HT signaling pathway and visceral hypersensitivity in rats[J].Chin J Gastroenterol,2011,09:534-538.
[6]王艳杰,关洪全,柴纪严,等.眼针对腹泻型肠易激综合征模型大鼠结肠P物质表达的影响[J].中华中医药杂志,2011,26(10):2268-2271.Wang YJ,Guan HQ,Cai JY,et al.Effects of eye-acupuncture therapy on expression of SP rats with irritable bowel syndrome[J].Chin J Tradit Chin Med Pharm,2011,26(10):2268-2271
[7]Johnson AC,Tran L,Schulkin J,et al.Importance of stress receptor-mediated mechanisms in the amygdala on visceral pain perception in an intrinsically anxious rat[J].Neurogastroenterol Motil,2012,24(5):479-486.
[8]刘晓丽,阎芳,王琳,等CRF、UCN1和CRFR1在肠易激综合征大鼠结肠中变化的研究[J].时珍国医国药,2012,23(6):1542-1545.Liu XL,Yan F,Wang L,et al.The expression of CRF,UCN1and CRFR1 in the colon of irritable bowel syndrome[J].Lishizhen Med Mater Med Res,2012,23(6):1542-1545.
[9]Keszthelyi D,Troost FJ,Jonkers DM,et al.Alterations in mucosal neuropeptides in patients with irritable bowel syndrome and ulcerative colitis in remission:A role in pain symptom generation?[J].Eur J Pain,2013,17(9):1299-1306.
[10]肖小芹,舒圆月,邓桂明,等.乌药水提液对腹泻型肠易激综合征模型大鼠Ghrelin、MTL、SP、Sec水平的影响[J].湖南中医药大学学报,2017,37(05):477-480.Xiao XQ,Shu YY,Deng GM,et al.Effect of water extract of Lindera Aggregata on Ghrelin,MTL,SP and Sec levels in rats with diarrhea-predominant irritable bowel syndrome[J].J Hunan Univ Chin Med,2017,37(05):477-480.
[11]Bravo JA,Dinan TG,Cryan JF.Alterations in the central CRF system of two different rat models of comorbid depression and functional gastrointestinal disorders[J].Int J Neuropsychopharmacol,2011,14(5):666-683.
[12]Kiank C,TachéY,Larauche M.Stress-related modulation of inflammation in experimental models of bowel disease and postinfectious irritable bowel syndrome:role of corticotropin releasing factor receptors[J].Brain Behav Immunity,2010,24(1):41-48.