摘要
目的:探讨小檗碱(Ber)对抑郁大鼠结肠动力学改变导致肠易激综合征(抑郁IBS)的影响及其机制。方法:选取SPF级成年SD雄性大鼠,分为对照组、抑郁IBS组和抑郁IBS+Ber干预组(Ber组),各15只。抑郁IBS模型是给大鼠28 d的孤养加慢性温和不可预知性应激刺激方式,再经相关检测确定,Ber组的抑郁IBS大鼠行连续灌胃Ber 14 d。比较各组大鼠的临床表现、旷场试验(OFT)、液体消耗试验(FCT)、排便和直结肠扩张实验(CRD),明确Ber对抑郁IBS大鼠的症状改善;酶解法分离3组大鼠的单个结肠平滑肌细胞,全细胞膜片钳技术记录它们的L-型钙电流(ICa-L)及其电流-电压曲线,探讨Ber作用抑郁IBS的离子通道机制。结果:与抑郁IBS组比较,Ber组大鼠的粪便性状好转,活跃度增加,体质和饮食变好,体质量显著增加(P<0.05);该组大鼠穿越格数、前腿竖立次数、理毛时间以及糖水消耗、纯水消耗和糖水偏爱率均明显增加(均P<0.01);另外,Ber组大鼠排出粪粒数及其含水量明显减少,反映直结肠敏感性、运动指数及其变化率均显著降低或减慢(与抑郁IBS组比较,均P<0.01),且恢复到对照组的状态(均P>0.05);最后,与抑郁IBS组比较,Ber组大鼠结肠平滑肌细胞ICa-L在各钳制电压下均明显减少,电流-电压曲线明显上抬而接近对照组;当钳制电压为+10 mV时,其电流密度为(10.91±0.37)pA/pF,明显小于抑郁IBS组的(14.91±1.23)pA/pF(P<0.01),而略大于对照组的(8.20±0.65)pA/pF(P>0.05)。结论:抑郁IBS大鼠经Ber作用后,其临床症状和原有情绪低落的负性活动与偏爱以及结肠出现的敏感性和蠕动失常状态均得到好转与改善,其机制可能与Ber抑制了抑郁IBS大鼠结肠平滑肌细胞ICa-L,纠正了其离子通道发生明显电重构。
Objective:To investigate the effects and mechanism of berberine(Ber)on irritable bowel syndrome(IBS)caused by depression induced abnormal colon motility in rats.Methods:The male Sprauge-Dawley rats with SPFgrade were divided into normal control,depression IBS and depression IBS+Ber group(Ber group)(n=15 per group).The model of depression IBS was established via using separation and chronic unpredictable mild stress for 28 days,and justified successfully by changes of parameters of clinical symptoms and open field test(OFT)as well as fluid consumption test(FCT)in rats.The rats in Ber group were treated with continuous lavage with Ber extracting solution for 14 days.Results of OFT,FCT and colorectal distension(CRD),and clinical symptoms in three groups were measured and compared to evaluate the effect of Ber administration on depression IBS.Single rat colonic myocyte was dissociated enzymatically,L-type calcium current(ICa-L)and its current-voltage(I-V)curve were recorded via whole-cell patch clamp technique,and the ion channel mechanism of treatment with Ber on depression IBS in rats was studied.Results:To compared with the depression IBS group,the clinical symptoms were all improved,such as the fecal particles were become more dry,and the physique and appetite increased significantly(P<0.05),and parameters or scores of OFT and FCT were notably improved in rats of different groups(P of all<0.01).Moreover,the fecal particles and water weight in the fetal were obviously decreased,and abdominal withdrawal reflex increased,as well as the colonic motility index and its change rate were significantly decreased in depression IBS rats administrated with Ber(P of all<0.01).Finally,ICa-L was significantly decreased under different membrane voltage,and the I-V curve was notably lifted to close to the level of control group in colonic cells of rats in Ber group.Under the voltage clamp of+10 mV,current density of ICa-L in colonic cells of rats was(14.91±1.23)pA/pF in depression IBS group,which was significant higher than that in Ber group(vs[10.91±0.37]pA/pF,P<0.01),and was close to that in control group(vs[8.20±0.65]pA/pF,P>0.05).Conclusion:It suggests that berberine could improve the clinical symptoms,and change the negative activities and favorites,as well as decrease the sensitivity and motility of gastrointestinal tract of depression IBS rats.Thus berberine might significantly inhibit the ICa-L induced the electrical remodeling of colonic cells of depression IBS rats.
作者
柴红
吴平亚
杨政
吴承云
谭诗云
罗和生
CHAI Hong;WU Pingya;YANG Zheng;WU Chengyun;TAN Shiyun;LUO Hesheng(Dept.of Gastroenterology,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China;Hongshan District Zhangjiawan Street Community Health Service Centre,Wuhan 430065,Hubei,China)
出处
《武汉大学学报（医学版）》
CAS
2020年第1期29-34,共6页
Medical Journal of Wuhan University
基金
国家自然科学基金资助项目(编号:30871248).
关键词
小檗碱
肠易激综合征
负性活动
肠动力学失常
L-型钙电流
电重构
Berberine
Irritable Bowel Syndrome
Negative Activity
Abnormal Colon Motility
L-type Calcium Current
Electrical Remodeling
作者简介
柴红,女,1973-,医学硕士,主要从事消化道疾病的基础与临床研究,E-mail:chaihong128@126.com
