复方诃子口服液抗犊牛大肠杆菌性腹泻的药理作用研究
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摘要
试验旨在研究抗犊牛大肠杆菌性腹泻的复方诃子口服液的药理作用,采用中和毒素试验、抗渗出试验、解热试验、镇痛试验、肠蠕动试验及免疫调节试验的方法,验证复方诃子口服液的药理作用。结果显示,抗毒素中和试验中,复方诃子口服液组与阴性对照组差异极显著(P<0.01)。抗渗出试验中,各药物组均能不同程度地减少伊文思蓝的渗出,阿司匹林组及复方诃子口服液高、中、低剂量组的抑制率分别为58.1%、42.8%、31.6%和14.9%,其中复方诃子口服液低剂量组与空白组相比差异显著(P<0.05),其余各组与空白组相比均差异极显著(P<0.01);复方诃子口服液各剂量组与阿司匹林组相比,高剂量组差异不显著(P>0.05),中、低剂量组差异极显著(P<0.01)。解热试验中,复方诃子口服液高剂量组给药后1h快速抑制体温升高,中剂量组给药后2h抑制体温升高;给药后3h,与模型组相比,复方诃子口服液高、中剂量组体温均明显降低,低剂量组与模型组差异不明显。镇痛试验中,与空白组相比,阿司匹林组、复方诃子口服液高、中剂量组镇痛效果差异极显著(P<0.01),扭体抑制率分别为64.55%、52.73%和32.73%,疼痛潜伏期分别为9.59、6.33和5.74min;而复方诃子口服液低剂量组差异不显著(P>0.05)。肠蠕动试验中,与空白组相比,硫酸阿托品组及复方诃子口服液高剂量组对肠蠕动抑制作用差异极显著(P<0.01),推进率分别为44.18%和52.55%,复方诃子口服液中剂量组差异显著(P<0.05),低剂量组差异不显著(P>0.05)。免疫调节试验中,与空白组相比,模型组白细胞数、脾脏指数及胸腺指数均显著降低(P<0.05);而与模型组相比,第14天复方诃子口服液组白细胞数、脾脏指数及胸腺指数均显著提高(P<0.05)。综上所述,复方诃子口服液对犊牛大肠杆菌性腹泻具有抑制肠蠕动、解热、抗疼痛和组织液渗出、中和肠毒素及增强免疫功能等药理作用。
The aim of the experiment was to study the pharmacological effects of compound Myrobalanoral liquid against Escherichia coli(E.coli)diarrhea in calves.We used neutralize enterotoxin test,anti-exudation test,antipyretic test,analgesic test,intestinal peristalsis test and immunomodulation test to verify the pharmacological effects of compound Myrobalan oral liquid.Theresults showed that in the neutralize enterotoxin test,there was extremely significant difference between compound Myrobalanoral liquid and negative control groups(P<0.01).In the anti-exudation test,all drug groups could reduce the exudation of Evans blue to varying degrees,the inhibition rates of the aspirin group,compound Myrobalan oral liquid high,medium and low dose groups were 58.1%,42.8%,31.6% and 14.9%,respectively.Among them,the compound Myrobalanoral liquid low dose group was significantly different from blank group(P<0.05),while other groups were extremely significantly different from blank group(P<0.01).The compound Myrobalan oral liquid medium and low dose groups had extremely significant difference compared with aspirin group(P<0.01),but the compound Myrobalan oral liquid high dose group had no significant difference(P>0.05).In the antipyretic test,the high-dose group of compound Myrobalan oral liquid quickly inhibited the increase of body temperature 1hafter administration,and the increase of body temperature was inhibited 2hafter the administration in medium dose group;3h after the administration,the body temperature was significantly reduced in high and medium dose groups compared with model group;The difference between low dose and model groups was not significant.In the anti-analgesic test,there were extremely significant differences in aspirin group,compound Myrobalanoral liquid high and medium dose groups compared with blank group(P<0.01),the writhing inhibition rates were 64.55%,52.73%and 32.73%,respectively,the pain latency were 9.59,6.33 and 5.74min;And there was no significant difference in low dose group(P>0.05).In the intestinal peristalsis test,compared with blank group,compound Myrobalan oral liquid high dose and atropine sulphate groups had obviously inhibitory effect on intestinal peristalsis(P<0.01),and the promotion rates were 44.18% and 52.55%,respectively;The effect of medium dose group of compound Myrobalan oral liquid was significant different(P<0.05),low dose group of compound Myrobalanoral liquid was not significant(P>0.05).In the immunomodulation test,the white blood cell(WBC)count,spleen and thymus organ indexes in model group were significantly lower than those in blank group(P<0.05),and the WBC count,spleen and thymus organ indexes in compound Myrobalan oral liquid group were significantly higher than those in model group on the 14 th day(P<0.05).In conclusion,compound Myrobalan oral liquid had neutralize enterotoxin,anti-exudation of tissue fluid,antipyretic,analgesia and inhibitory effect on intestinal peristalsis of E.coli diarrhea,and could enhance the immune function and other pharmacological effects.
The aim of the experiment was to study the pharmacological effects of compound Myrobalanoral liquid against Escherichia coli(E.coli)diarrhea in calves.We used neutralize enterotoxin test,anti-exudation test,antipyretic test,analgesic test,intestinal peristalsis test and immunomodulation test to verify the pharmacological effects of compound Myrobalan oral liquid.Theresults showed that in the neutralize enterotoxin test,there was extremely significant difference between compound Myrobalanoral liquid and negative control groups(P<0.01).In the anti-exudation test,all drug groups could reduce the exudation of Evans blue to varying degrees,the inhibition rates of the aspirin group,compound Myrobalan oral liquid high,medium and low dose groups were 58.1%,42.8%,31.6% and 14.9%,respectively.Among them,the compound Myrobalanoral liquid low dose group was significantly different from blank group(P<0.05),while other groups were extremely significantly different from blank group(P<0.01).The compound Myrobalan oral liquid medium and low dose groups had extremely significant difference compared with aspirin group(P<0.01),but the compound Myrobalan oral liquid high dose group had no significant difference(P>0.05).In the antipyretic test,the high-dose group of compound Myrobalan oral liquid quickly inhibited the increase of body temperature 1hafter administration,and the increase of body temperature was inhibited 2hafter the administration in medium dose group;3h after the administration,the body temperature was significantly reduced in high and medium dose groups compared with model group;The difference between low dose and model groups was not significant.In the anti-analgesic test,there were extremely significant differences in aspirin group,compound Myrobalanoral liquid high and medium dose groups compared with blank group(P<0.01),the writhing inhibition rates were 64.55%,52.73%and 32.73%,respectively,the pain latency were 9.59,6.33 and 5.74min;And there was no significant difference in low dose group(P>0.05).In the intestinal peristalsis test,compared with blank group,compound Myrobalan oral liquid high dose and atropine sulphate groups had obviously inhibitory effect on intestinal peristalsis(P<0.01),and the promotion rates were 44.18% and 52.55%,respectively;The effect of medium dose group of compound Myrobalan oral liquid was significant different(P<0.05),low dose group of compound Myrobalanoral liquid was not significant(P>0.05).In the immunomodulation test,the white blood cell(WBC)count,spleen and thymus organ indexes in model group were significantly lower than those in blank group(P<0.05),and the WBC count,spleen and thymus organ indexes in compound Myrobalan oral liquid group were significantly higher than those in model group on the 14 th day(P<0.05).In conclusion,compound Myrobalan oral liquid had neutralize enterotoxin,anti-exudation of tissue fluid,antipyretic,analgesia and inhibitory effect on intestinal peristalsis of E.coli diarrhea,and could enhance the immune function and other pharmacological effects.
引文
[1]王丽华.犊牛大肠杆菌病的综合防治[J].中国动物保健,2012,9:45-46.WANG L H.Integrated control of E.coli disease in calf[J].China Animal Health,2012,9:45-46.(in Chinese)
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[6]蒋禄峰,秦建华,张梦茜,等.两种中药方剂对奶牛感染性腹泻的治疗效果[J].动物医学进展,2013,34(2):131-133.JIANG L F,QIN J H,ZHANG M Q,et al.Therapeutic effect of two prescriptions of Chinese traditional medicines for bovine infectious diarrhea[J].Progress in Veterinary Medicine,2013,34(2):131-133.(in Chinese)
[7]徐丹丹.抗细菌性犊牛腹泻中药颗粒剂的研究[D].哈尔滨:东北农业大学,2010.XU D D.Studies on the traditional Chinese medicine granules against bacteria caused calf diarrhea[D].Harbin:Northeast Agricultural University,2010.(in Chinese)
[8]毛莹,张贵君,张智圆.葛根芩连汤药效组分抗腹泻药效学研究[J].辽宁中医杂志,2013,7:1433-1435.MAO Y,ZHANG G J,ZHANG Z Y.Pharmacodynamics study on anti-diarrhea of active componentions alignment in Gegen Qinlian decoction[J].Liaoning Journal of Traditional Chinese Medicine,2013,7:1433-1435.(in Chinese)
[9]徐雯,王楠,丁浩然,等.广藿香对湿阻中焦证大鼠胃肠功能的影响[J].中国中药杂志,2017,42(23):4649-4655.XU W,WANG N,DING H R,et al.Effects of patchouli on gastrointestinal function in rats with dampness resistance[J].Chinese Journal of Traditional Chinese Medicine,2017,42(23):4649-4655.(in Chinese)
[10]郝一妹,张焕容.牦牛源产肠毒素性大肠杆菌血清型和毒力基因调查[J].中国兽医杂志,2015,51(1):51-52.HAO Y M,ZHANG H R.Investigation on serotypes and virulence genes of enterotoxigenic E.coli from yak[J].Chinese Journal of Veterinary Medicine,2015,51(1):51-52.(in Chinese)
[11]于文会,李叔洪,姜晓文,等.黄连组方对大肠杆菌O78的抑菌作用与临床疗效研究[J].中国畜牧兽医,2018,45(3):814-821.YU W H,LI S H,JIANG X W,et al.Study on the antimicrobial activity and clinical efficacy of Coptis chinensis prescription on E.coli O78[J].China Journal of Animal Husbandry&Veterinary Medicine,2018,45(3):814-821.(in Chinese)
[12]KIM E,AHN S,RHEE H I,et al.Coptis chinensis Franch.extract up-regulate typeⅠhelper T-cell cytokine through MAPK activation in MOLT-4 Tcell[J].Journal of Ethnopharmacology,2016,189:126-131.
[13]秦传,刘勇,云海.不同粉碎度板蓝根抗细菌内毒素作用[J].医药导报,2012,31(11):1427-1429.QIN C,LIU Y,YUN H.The effect of antibacterial endotoxin by radix isatidis at different particle size[J].Herald of Medicine,2012,31(11):1427-1429.(in Chinese)
[14]李振,李萍,唐健萍.22种中草药体外抗菌作用的研究[J].实验室科学,2013,16(5):9-12.LI Z,LI P,TANG J P.Study on antibacterial activity of 22Chinese herbal medicine in vitro[J].Laboratory Science,2013,16(5):9-12.(in Chinese)
[15]赵娟,白元生,武果桃,等.益气健脾中药对腹泻仔猪小肠黏膜组织结构的影响[J].中国畜牧兽医,2014,41(11):252-257.ZHAO J,BAI Y S,WU G T,et al.Effect of Tonifying Qi-Nourishing Spleen herbs on small intestinal mucosa in diarrheal piglets[J].China Animal Husbandry&Veterinary Medicine,2014,41(11):252-257.(in Chinese)
[16]吴穹,寇毅英,李瑞莲.十八味党参丸抗炎镇痛作用的实验研究[J].青海医学院学报,2015,36(2):141-144.WU Q,KOU Y Y,LI R L.The experimental study on the anti-inflammatory and analgesic effects of eighteen flavor dangshen pill(EFDSP)[J].Journal of Qinghai Medical College,2015,36(2):141-144.(in Chinese)
[17]张柏娥,张琳,孙敏,等.黄连与吴茱萸经典配伍系列解热作用研究[J].云南中医学院学报,2017,40(4):43-46.ZHANG B E,ZHANG L,SUN M,et al.Study of relieving fever effect on classical similar prescriptions of Coptis chinensis and Evodiae rutaecarpa[J].Journal of Yunnan College of Traditional Chinese Medicine,2017,40(4):43-46.(in Chinese)
[18]斯琴高娃,包勒朝鲁,李敏.黄连中小檗碱药理活性的研究进展[J].中国民族医药杂志,2014,20(1):49-52.SIQIN G W,BAOLE C L,LI M.Research progress of pharmacological activity of berberine in Coptis chinensis[J].Journal of Medicine&Pharmacy of Chinese Minorities,2014,20(1):49-52.(in Chinese)
[19]刘卫霞,王俊平,林立红,等.黄连解毒汤的镇痛、抗炎及体内抗肿瘤作用[J].沈阳医学院学报,2013,15(1):53-55.LIU W X,WANG J P,LIN L H,et al.Nalgesic,antiinflammatory and in vivo antitumor effects of Huanglianjiedu decoction[J].Journal of Shenyang Medical College,2013,15(1):53-55.(in Chinese)
[20]惠毅,闫曙光,周永学.乌梅丸及其拆方对溃疡性结肠炎大鼠胃肠功能影响的实验研究[J].陕西中医,2013,11:1556-1558.HUI Y,YAN S G,ZHOU Y X.Experimental study on effect of Wumei pill and its disassembled prescription on gastrointestinal function in rats with ulcerative colitis[J].Shaanxi Journal of Traditional Chinese Medicine,2013,11:1556-1558.(in Chinese)
[21]杨奕樱,潘春,张秋方,等.双白半水提浸膏对环磷酰胺致免疫功能低下小鼠免疫功能的影响[J].河南中医,2017,37(7):1190-1192.YANG Y Y,PAN C,ZHANG Q F,et al.Effect of double white and half water extract on immunological function of mice induced by cyclophosphamide[J].Henan Traditional Chinese Medicine,2017,37(7):1190-1192.(in Chinese)
[22]CHEN W,SRINIVASAN S R,XU J,et al.Blackwhite divergence in the relation of white blood cell count to metabolic syndrome in preadolescents,adolescents,and young adults:The bogalusa heart study[J].Diabetes Care,2010,33(11):2474-2476.
[23]韦风华.环磷酰胺临床应用研究进展[J].中国药事,2013,27(3):324-326.WEI F H.Progress in clinical application of cyclophosphamide[J].China Pharmaceutical Affairs,2013,27(3):324-326.(in Chinese)
[2]李彬,王开拓.犊牛腹泻的病因与防治[J].中兽医学杂志,2017,2:26.LI B,WANG K T.Causes and prevention of calf diarrhea[J].Chinese Journal of Veterinary Medicine,2017,2:26.(in Chinese)
[3]温建军,徐雪芳.肠侵袭性大肠杆菌致病机制的研究进展[J].中国动物检疫,2012,29(1):60-63.WEN J J,XU X F.Advances in pathogenesis of intestinal invasive E.coli[J].China Animal Health Inspection,2012,29(1):60-63.(in Chinese)
[4]王传春,袁东方,孙秋艳,等.禽致病性大肠杆菌的分离鉴定及致病性研究[J].山东畜牧兽医,2017,38(3):8-9.WANG C C,YUAN D F,SUN Q Y,et al.Isolation,identification and pathogenicity of avian pathogenic E.coli[J].Shandong Journal of Animal Husbandry&Veterinary Medicine,2017,38(3):8-9.(in Chinese)
[5]杨新玲.浅论泄泻与湿邪的关系[J].世界最新医学信息文摘,2015,91:115-116.YANG X L.The relationship between diarrhea and wetness[J].World Latest Medicine Information,2015,91:115-116.(in Chinese)
[6]蒋禄峰,秦建华,张梦茜,等.两种中药方剂对奶牛感染性腹泻的治疗效果[J].动物医学进展,2013,34(2):131-133.JIANG L F,QIN J H,ZHANG M Q,et al.Therapeutic effect of two prescriptions of Chinese traditional medicines for bovine infectious diarrhea[J].Progress in Veterinary Medicine,2013,34(2):131-133.(in Chinese)
[7]徐丹丹.抗细菌性犊牛腹泻中药颗粒剂的研究[D].哈尔滨:东北农业大学,2010.XU D D.Studies on the traditional Chinese medicine granules against bacteria caused calf diarrhea[D].Harbin:Northeast Agricultural University,2010.(in Chinese)
[8]毛莹,张贵君,张智圆.葛根芩连汤药效组分抗腹泻药效学研究[J].辽宁中医杂志,2013,7:1433-1435.MAO Y,ZHANG G J,ZHANG Z Y.Pharmacodynamics study on anti-diarrhea of active componentions alignment in Gegen Qinlian decoction[J].Liaoning Journal of Traditional Chinese Medicine,2013,7:1433-1435.(in Chinese)
[9]徐雯,王楠,丁浩然,等.广藿香对湿阻中焦证大鼠胃肠功能的影响[J].中国中药杂志,2017,42(23):4649-4655.XU W,WANG N,DING H R,et al.Effects of patchouli on gastrointestinal function in rats with dampness resistance[J].Chinese Journal of Traditional Chinese Medicine,2017,42(23):4649-4655.(in Chinese)
[10]郝一妹,张焕容.牦牛源产肠毒素性大肠杆菌血清型和毒力基因调查[J].中国兽医杂志,2015,51(1):51-52.HAO Y M,ZHANG H R.Investigation on serotypes and virulence genes of enterotoxigenic E.coli from yak[J].Chinese Journal of Veterinary Medicine,2015,51(1):51-52.(in Chinese)
[11]于文会,李叔洪,姜晓文,等.黄连组方对大肠杆菌O78的抑菌作用与临床疗效研究[J].中国畜牧兽医,2018,45(3):814-821.YU W H,LI S H,JIANG X W,et al.Study on the antimicrobial activity and clinical efficacy of Coptis chinensis prescription on E.coli O78[J].China Journal of Animal Husbandry&Veterinary Medicine,2018,45(3):814-821.(in Chinese)
[12]KIM E,AHN S,RHEE H I,et al.Coptis chinensis Franch.extract up-regulate typeⅠhelper T-cell cytokine through MAPK activation in MOLT-4 Tcell[J].Journal of Ethnopharmacology,2016,189:126-131.
[13]秦传,刘勇,云海.不同粉碎度板蓝根抗细菌内毒素作用[J].医药导报,2012,31(11):1427-1429.QIN C,LIU Y,YUN H.The effect of antibacterial endotoxin by radix isatidis at different particle size[J].Herald of Medicine,2012,31(11):1427-1429.(in Chinese)
[14]李振,李萍,唐健萍.22种中草药体外抗菌作用的研究[J].实验室科学,2013,16(5):9-12.LI Z,LI P,TANG J P.Study on antibacterial activity of 22Chinese herbal medicine in vitro[J].Laboratory Science,2013,16(5):9-12.(in Chinese)
[15]赵娟,白元生,武果桃,等.益气健脾中药对腹泻仔猪小肠黏膜组织结构的影响[J].中国畜牧兽医,2014,41(11):252-257.ZHAO J,BAI Y S,WU G T,et al.Effect of Tonifying Qi-Nourishing Spleen herbs on small intestinal mucosa in diarrheal piglets[J].China Animal Husbandry&Veterinary Medicine,2014,41(11):252-257.(in Chinese)
[16]吴穹,寇毅英,李瑞莲.十八味党参丸抗炎镇痛作用的实验研究[J].青海医学院学报,2015,36(2):141-144.WU Q,KOU Y Y,LI R L.The experimental study on the anti-inflammatory and analgesic effects of eighteen flavor dangshen pill(EFDSP)[J].Journal of Qinghai Medical College,2015,36(2):141-144.(in Chinese)
[17]张柏娥,张琳,孙敏,等.黄连与吴茱萸经典配伍系列解热作用研究[J].云南中医学院学报,2017,40(4):43-46.ZHANG B E,ZHANG L,SUN M,et al.Study of relieving fever effect on classical similar prescriptions of Coptis chinensis and Evodiae rutaecarpa[J].Journal of Yunnan College of Traditional Chinese Medicine,2017,40(4):43-46.(in Chinese)
[18]斯琴高娃,包勒朝鲁,李敏.黄连中小檗碱药理活性的研究进展[J].中国民族医药杂志,2014,20(1):49-52.SIQIN G W,BAOLE C L,LI M.Research progress of pharmacological activity of berberine in Coptis chinensis[J].Journal of Medicine&Pharmacy of Chinese Minorities,2014,20(1):49-52.(in Chinese)
[19]刘卫霞,王俊平,林立红,等.黄连解毒汤的镇痛、抗炎及体内抗肿瘤作用[J].沈阳医学院学报,2013,15(1):53-55.LIU W X,WANG J P,LIN L H,et al.Nalgesic,antiinflammatory and in vivo antitumor effects of Huanglianjiedu decoction[J].Journal of Shenyang Medical College,2013,15(1):53-55.(in Chinese)
[20]惠毅,闫曙光,周永学.乌梅丸及其拆方对溃疡性结肠炎大鼠胃肠功能影响的实验研究[J].陕西中医,2013,11:1556-1558.HUI Y,YAN S G,ZHOU Y X.Experimental study on effect of Wumei pill and its disassembled prescription on gastrointestinal function in rats with ulcerative colitis[J].Shaanxi Journal of Traditional Chinese Medicine,2013,11:1556-1558.(in Chinese)
[21]杨奕樱,潘春,张秋方,等.双白半水提浸膏对环磷酰胺致免疫功能低下小鼠免疫功能的影响[J].河南中医,2017,37(7):1190-1192.YANG Y Y,PAN C,ZHANG Q F,et al.Effect of double white and half water extract on immunological function of mice induced by cyclophosphamide[J].Henan Traditional Chinese Medicine,2017,37(7):1190-1192.(in Chinese)
[22]CHEN W,SRINIVASAN S R,XU J,et al.Blackwhite divergence in the relation of white blood cell count to metabolic syndrome in preadolescents,adolescents,and young adults:The bogalusa heart study[J].Diabetes Care,2010,33(11):2474-2476.
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