肝郁脾虚型IBS-D大鼠模型的建立与评价
|
摘要
目的:建立一种符合腹泻型肠易激综合征(diarrhea-irritable bowel syndrome,IBS-D)肝郁脾虚型病理特征的大鼠模型。方法:将22只雄性Sprague Dawley(SD)大鼠通过基线期评测后,符合纳入标准的健康大鼠随机分入空白对照组、模型组。对模型组采用番泻叶浸剂灌胃结合慢性不可预知轻度应激(chronic unpredictable mild stress,CUMS)造模,空白对照组除蒸馏水灌胃外不予任何干预,连续造模14天。造模后进行腹泻指数观测,腹壁撤退反射实验,糖水偏嗜实验(sucrose preference test,SPT)以及高架十字迷宫(elevated plus maze,EPM)实验,结合大鼠的一般情况、体质量增长情况以及进食量变化综合评判造模结果。结果:基线期排除率为9.09%,造模过程死亡率为8.33%,模型成功率为63.64%。与空白对照组相比,模型组大鼠进食量明显降低(P=0.000);体质量增长明显减缓(P=0.008);腹泻指数以及内脏敏感性较空白对照组明显升高(P=0.000);EPM开臂时间比较空白对照组明显降低(P=0.000);在SPT中糖水偏好指数明显降低(P=0.001)。结论:应用番泻叶浸剂灌胃结合CUMS造模后,模型大鼠符合IBS-D肝郁脾虚证型特点,是一种较好的造模方式。
Objective:To establish a rat model which is consistent with liver depression and spleen deficiency syndrome(LDSDS) pathophysiological characteristics of diarrhea-irritable bowel syndrome(IBS-D).Methods:Twenty-two male Sprague Dawley(SD)rats,passed through baseline testing,and complied with inclusion criteria were randomly divided into blank control group and model group.The model group was treated with senna extract gavage combined with chronic unpredictable mild stress(CUMS) modeling mode,and the blank control group was treated with distilled water by gavage without any other intervention,continuously modeling for 14 days.After the model was established,the diarrhea index was observed,the abdominal wall withdrawal reflex experiment,the sucrose preference tests(SPT) and the elevated plus maze(EPM)tests were carried out,combined with the general performance of rats,weight gain and changes of food intake to comprehensively judge the TCM syndrome.Results:The baseline elimination rate was 9.09%,the mortality rate of the modeling process was 8.33%,and the model success rate was 63.64%.Compared with the control group,the change of food intake in the model group was significantly lower(P=0.000).The weight gain was significantly slowed down(P=0.008).The diarrhea index and visceral sensitivity of the model group rats were higher(P=0.000).The rate of open-arm time in the EPM of model group was lower(P=0.000) and the sugar water preference index in SPT of model group was significantly decreased(P=0.000).Conclusion:The model rats,treated with senna extract by gavage combined with CUMS modeling mode,were consistent with the characteristics of LDSDS of IBS-D,and it was a good modeling method.
Objective:To establish a rat model which is consistent with liver depression and spleen deficiency syndrome(LDSDS) pathophysiological characteristics of diarrhea-irritable bowel syndrome(IBS-D).Methods:Twenty-two male Sprague Dawley(SD)rats,passed through baseline testing,and complied with inclusion criteria were randomly divided into blank control group and model group.The model group was treated with senna extract gavage combined with chronic unpredictable mild stress(CUMS) modeling mode,and the blank control group was treated with distilled water by gavage without any other intervention,continuously modeling for 14 days.After the model was established,the diarrhea index was observed,the abdominal wall withdrawal reflex experiment,the sucrose preference tests(SPT) and the elevated plus maze(EPM)tests were carried out,combined with the general performance of rats,weight gain and changes of food intake to comprehensively judge the TCM syndrome.Results:The baseline elimination rate was 9.09%,the mortality rate of the modeling process was 8.33%,and the model success rate was 63.64%.Compared with the control group,the change of food intake in the model group was significantly lower(P=0.000).The weight gain was significantly slowed down(P=0.008).The diarrhea index and visceral sensitivity of the model group rats were higher(P=0.000).The rate of open-arm time in the EPM of model group was lower(P=0.000) and the sugar water preference index in SPT of model group was significantly decreased(P=0.000).Conclusion:The model rats,treated with senna extract by gavage combined with CUMS modeling mode,were consistent with the characteristics of LDSDS of IBS-D,and it was a good modeling method.
引文
[1] Chey WD,Kurlander J,Eswaran S.Irritable bowel syndrome:a clinical review[J].JAMA,2015,313(9):949-958.
[2] 张科,曹蕊芸,诸孟娟,等.腹泻型肠易激综合征中医证型与焦虑、抑郁状态的相关性研究[J].辽宁中医杂志,2016,43(1):89-91.
[3] Mayer EA.Clinical practice.Irritable bowel syndrome[J].N Engl J Med,2008,358(16):1692-1699.
[4] Wang W,Wang F,Fan F,et al.Mind-Body Interventions for Irritable Bowel Syndrome Patients in the Chinese Population:a Systematic Review and Meta-Analysis[J].International Journal of Behavior Medicine,2017,24(2):191-204.
[5] 吴皓萌,徐志伟,敖海清,等.基于中医四诊和脑肠肽的腹泻型肠易激综合征中医证候判别研究[J].中国中西医结合杂志,2015,35(10):1200-1204.
[6] 张北华.IBS-D肝郁脾虚型病证结合大鼠模型的建立与评价[D].北京:中国中医科学院,2013.
[7] Chao GQ,Zhang S.Effectiveness of acupuncture to treat irritable bowel syndrome:a meta-analysis[J].World J Gastroenterol,2014,20(7):1871-1877.
[8] 滕茜华,李德勤.不同浸出时间和方法对番泻叶有效成分的影响[J].时珍国药研究,1991,2(2):75-80.
[9] 林观样,潘晓军,蔡进章.不同浸泡方法对番泻叶中番泻苷A浸出率的影响比较[J].医药导报,2006,25(8):816-817.
[10] 周思远,赵妍,李瑛,等.一种抽屉式大鼠观察箱:中国,ZL201620929271.X[P].2016-08-23.
[11] 刘美荣,肖瑞飞,彭芝配,等.针刺“足三里”“太冲”穴对腹泻型肠易激综合征大鼠胃肠激素的影响[J].针刺研究,2012,37(5):363-368.
[12] 安荣,韩佩玉,徐秋颖,等.肠易激综合征动物模型的建立及评价[J].新乡医学院学报,2016(5):434-439.
[13] 王鹏.肠易激综合征肠上皮—肠胶质细胞网络调控异常的分子机制研究[D].济南:山东大学,2015.
[14] 姚弘,魏大能,蔡定均,等.针刺对慢性情绪应激焦虑大鼠肾上腺ANP、CNP及血浆CORT水平的影响[J].中国针灸,2016,36(2):169-174.
[15] 刘昊,徐爱军,秦丽娟,等.人参皂苷Rb1对抑郁症大鼠海马5-HT及5-HT1A受体表达的影响[J].时珍国医国药,2014,25(11):2565-2567.
[16] 袁旭,蔡定均,赵纪岚,等.电针对慢性情绪应激焦虑大鼠中枢5-HT含量及其代谢物水平的影响[J].时珍国医国药,2014,25(11):2787-2789.
[17] 蒋希荣,任路,毛亮.以“肾脑相济”理论为指导的电针疗法对围绝经期抑郁症模型大鼠行为学及下丘脑-垂体-肾上腺影响[J].辽宁中医杂志,2016,43(8):1752-1754.
[18] 赵妍,罗丹妮,陈颖,等.慢性束缚应激联合番泻叶灌胃法制备IBS-D大鼠模型的量效及时效关系评价[J].世界华人消化杂志,2017,25(15):1360-1367.
[19] 黄文琴,魏大能,周奇志,等.电针对焦虑大鼠胸腺组织形态、心钠肽和利钠肽受体-A表达的影响[J].中国中西医结合杂志,2016,36(2):216-221.
[20] La JH,Sung TS,Kim HJ,et al.Peripheral corticotropin releasing hormone mediates post-inflammatory visceral hypersensitivity in rats[J].World J Gastroenterol,2008,14(5):731-736.
[21] 杨勇,张艳峰,郭曲练,等.神经病理性痛大鼠母爱行为对子鼠情绪及杏仁核DNA甲基化的影响[J].中华麻醉学杂志,2016,36(7):831-834.
[22] Mayer EA,NalibofI BD,Chang L,et al.V.Stress and irritable bowel syndrome[J].Am J Physiol Gastrointest Liver Physiol,2001,280(4):G519-G524.
[23] 岳利峰,丁杰,陈家旭,等.肝郁脾虚证大鼠模型的建立与评价[J].北京中医药大学学报,2008,31(6):396-400.
[24] 李宁,唐启盛,赵瑞珍,等.慢性焦虑应激大鼠行为学的变化及高架十字迷宫的测评[J].中华中医药学刊,2010,28(4):711-713.
[25] Zhao YP,Tang XD,Bian ZX,et al.Preliminary study of establishing and assessing IBS-D model rats of gan stagnation and Pi deficiency syndrome[J].Zhongguo Zhong Xi Yi Jie He Za Zhi,2013,33(11):1507-1514. and assessing IBS-D model rats of gan stagnation and Pi deficiency syndrome[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi,2013,33(11):1507-1514.
[26]罗丹妮,赵妍,陈颖,等.肠易激综合征与性别相关性激素水平及免疫调节因素的关系[J].世界华人消化杂志,2017,25(6):504-508.
[27]宋素华,宋彬彬.肠易激综合征中医证候与焦虑、抑郁情绪的关系研究[J].中西医结合研究,2015,7(2):66-68,71.
[28] Yi L,Zhang H,Sun H,et al. Maternal separation induced visceral hypersensitivity from childhood to adulthood[J]. J Neurogastroenterol Motil,2017,23(2):306-315.
[29]魏盛,高杰,乔明琦.情志病证动物模型行为学评价应遵循的基本原则[J].山东中医药大学学报,2013,37(6):462-463.
[2] 张科,曹蕊芸,诸孟娟,等.腹泻型肠易激综合征中医证型与焦虑、抑郁状态的相关性研究[J].辽宁中医杂志,2016,43(1):89-91.
[3] Mayer EA.Clinical practice.Irritable bowel syndrome[J].N Engl J Med,2008,358(16):1692-1699.
[4] Wang W,Wang F,Fan F,et al.Mind-Body Interventions for Irritable Bowel Syndrome Patients in the Chinese Population:a Systematic Review and Meta-Analysis[J].International Journal of Behavior Medicine,2017,24(2):191-204.
[5] 吴皓萌,徐志伟,敖海清,等.基于中医四诊和脑肠肽的腹泻型肠易激综合征中医证候判别研究[J].中国中西医结合杂志,2015,35(10):1200-1204.
[6] 张北华.IBS-D肝郁脾虚型病证结合大鼠模型的建立与评价[D].北京:中国中医科学院,2013.
[7] Chao GQ,Zhang S.Effectiveness of acupuncture to treat irritable bowel syndrome:a meta-analysis[J].World J Gastroenterol,2014,20(7):1871-1877.
[8] 滕茜华,李德勤.不同浸出时间和方法对番泻叶有效成分的影响[J].时珍国药研究,1991,2(2):75-80.
[9] 林观样,潘晓军,蔡进章.不同浸泡方法对番泻叶中番泻苷A浸出率的影响比较[J].医药导报,2006,25(8):816-817.
[10] 周思远,赵妍,李瑛,等.一种抽屉式大鼠观察箱:中国,ZL201620929271.X[P].2016-08-23.
[11] 刘美荣,肖瑞飞,彭芝配,等.针刺“足三里”“太冲”穴对腹泻型肠易激综合征大鼠胃肠激素的影响[J].针刺研究,2012,37(5):363-368.
[12] 安荣,韩佩玉,徐秋颖,等.肠易激综合征动物模型的建立及评价[J].新乡医学院学报,2016(5):434-439.
[13] 王鹏.肠易激综合征肠上皮—肠胶质细胞网络调控异常的分子机制研究[D].济南:山东大学,2015.
[14] 姚弘,魏大能,蔡定均,等.针刺对慢性情绪应激焦虑大鼠肾上腺ANP、CNP及血浆CORT水平的影响[J].中国针灸,2016,36(2):169-174.
[15] 刘昊,徐爱军,秦丽娟,等.人参皂苷Rb1对抑郁症大鼠海马5-HT及5-HT1A受体表达的影响[J].时珍国医国药,2014,25(11):2565-2567.
[16] 袁旭,蔡定均,赵纪岚,等.电针对慢性情绪应激焦虑大鼠中枢5-HT含量及其代谢物水平的影响[J].时珍国医国药,2014,25(11):2787-2789.
[17] 蒋希荣,任路,毛亮.以“肾脑相济”理论为指导的电针疗法对围绝经期抑郁症模型大鼠行为学及下丘脑-垂体-肾上腺影响[J].辽宁中医杂志,2016,43(8):1752-1754.
[18] 赵妍,罗丹妮,陈颖,等.慢性束缚应激联合番泻叶灌胃法制备IBS-D大鼠模型的量效及时效关系评价[J].世界华人消化杂志,2017,25(15):1360-1367.
[19] 黄文琴,魏大能,周奇志,等.电针对焦虑大鼠胸腺组织形态、心钠肽和利钠肽受体-A表达的影响[J].中国中西医结合杂志,2016,36(2):216-221.
[20] La JH,Sung TS,Kim HJ,et al.Peripheral corticotropin releasing hormone mediates post-inflammatory visceral hypersensitivity in rats[J].World J Gastroenterol,2008,14(5):731-736.
[21] 杨勇,张艳峰,郭曲练,等.神经病理性痛大鼠母爱行为对子鼠情绪及杏仁核DNA甲基化的影响[J].中华麻醉学杂志,2016,36(7):831-834.
[22] Mayer EA,NalibofI BD,Chang L,et al.V.Stress and irritable bowel syndrome[J].Am J Physiol Gastrointest Liver Physiol,2001,280(4):G519-G524.
[23] 岳利峰,丁杰,陈家旭,等.肝郁脾虚证大鼠模型的建立与评价[J].北京中医药大学学报,2008,31(6):396-400.
[24] 李宁,唐启盛,赵瑞珍,等.慢性焦虑应激大鼠行为学的变化及高架十字迷宫的测评[J].中华中医药学刊,2010,28(4):711-713.
[25] Zhao YP,Tang XD,Bian ZX,et al.Preliminary study of establishing and assessing IBS-D model rats of gan stagnation and Pi deficiency syndrome[J].Zhongguo Zhong Xi Yi Jie He Za Zhi,2013,33(11):1507-1514. and assessing IBS-D model rats of gan stagnation and Pi deficiency syndrome[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi,2013,33(11):1507-1514.
[26]罗丹妮,赵妍,陈颖,等.肠易激综合征与性别相关性激素水平及免疫调节因素的关系[J].世界华人消化杂志,2017,25(6):504-508.
[27]宋素华,宋彬彬.肠易激综合征中医证候与焦虑、抑郁情绪的关系研究[J].中西医结合研究,2015,7(2):66-68,71.
[28] Yi L,Zhang H,Sun H,et al. Maternal separation induced visceral hypersensitivity from childhood to adulthood[J]. J Neurogastroenterol Motil,2017,23(2):306-315.
[29]魏盛,高杰,乔明琦.情志病证动物模型行为学评价应遵循的基本原则[J].山东中医药大学学报,2013,37(6):462-463.