出 处:《现代中西医结合杂志》2023年第12期1607-1616,共10页Modern Journal of Integrated Traditional Chinese and Western Medicine
基 金:国家自然科学基金项目(82060800);甘肃省青年科技基金计划项目(20JR10RA759);甘肃省卫生行业科技计划项目(GSWSKY2020-30);兰大二院萃英科技创新计划项目(CY2018-MS14);兰州市科技发展指导性计划项目(2019-ZD-71)。
摘 要:目的基于自主神经系统研究胃肠动力障碍性疾病(DGIMD)可能的发病机制及厚朴三物汤调控胃肠动力的作用机制。方法将40只雄性SD大鼠按计算机数字随机法分为对照组、模型组、厚朴三物汤组、α受体抑制剂组、β受体抑制剂组,每组8只。除对照组外,其余组均腹腔注射20%左旋精氨酸溶液5 d建立DGIMD模型,对照组注射等体积生理盐水。第6天开始,厚朴三物汤组给予厚朴三物汤4.725 g(生药)/(kg·d)灌胃,α受体抑制剂组给予酚苄明2.1 mg/(kg·d)灌胃[剂量逐渐增至4.2 mg/(kg·d)],β受体抑制剂组给予普萘洛尔2.1 mg/(kg·d)灌胃[剂量逐渐增至8.4 mg/(kg·d)],对照组与模型组给予等体积生理盐水灌胃,均每日2次,灌胃7 d。灌胃结束后,进行小肠推进率和胃排空率的测定,HE染色观察胃、空肠、结肠组织病理形态,ELISA法检测血及胃、空肠、结肠组织中去甲肾上腺素(NE)含量,RT-PCR法及Western blot法检测胃、空肠、结肠组织中去甲肾上腺素转运体(NET)mRNA及蛋白表达情况,免疫组织化学法检测胃、空肠、结肠组织中α_(1)、α_(2)、β_(1)、β_(2)型肾上腺素能受体阳性表达情况。结果模型组大鼠的胃排空率、小肠推进率均明显低于对照组(P均<0.05);厚朴三物汤组及α受体抑制剂组小肠推进率与胃排空率均明显高于模型组(P均<0.05)。各组大鼠胃、空肠、结肠组织解剖结构、腺体及肠绒毛完整,未见炎性细胞浸润。模型组大鼠血及胃、空肠、结肠组织中NE含量均明显高于对照组(P均<0.05),各药物组大鼠血及胃、空肠、结肠组织中NE含量均明显低于模型组(P均<0.05),但厚朴三物汤组大鼠血及胃、空肠、结肠组织中NE含量均明显高于α受体抑制剂组和β受体抑制剂组(P均<0.05)。模型组大鼠胃、空肠、结肠组织中NET mRNA表达量均明显低于对照组(P均<0.05),厚朴三物汤组、α受体抑制剂组大鼠胃、空肠、结肠组织中NEObjective It is to explore the possible pathogenesis of disorders of gastrointestinal motility diseases(DGIMD)and the mechanism of Houpu Sanwu decoction(HSD)in regulating gastrointestinal motility based on the autonomic nervous system.Methods Forty male SD rats were divided into control group,model group,HSD group,α-receptor inhibitor group,andβ-receptor inhibitor group according to the computerized numerical randomization method,with 8 rats in each group.The rats in all the groups except for the control group were injected intraperitoneally with 20%L-arginine solution for 5 d to establish DGIMD models,and the rats in the control group was injected intraperitoneally with an equal volume of normal saline.Starting from 6th day,the HSD group was given HSD 4.725 g(crude drug)/(kg·d)by gavage,theα-receptor inhibitor group was given phenobarbital 2.1 mg/(kg·d)by gavage[the dose was gradually increased to 4.2 mg/(kg·d)],and theβ-receptor inhibitor group was given propranolol 2.1 mg/(kg·d)by gavage[the dose was gradually increased to 8.4 mg/(kg·d)],the control and model groups were given equal volumes of saline by gavage,all twice daily,continuously treated for 7 days.At the end of gavage,the small intestinal propulsion rate and gastric emptying rate were detected,the histopathological morphology of the stomach,jejunum,and colon tissues were observed by HE staining,the contents of norepinephrine(NE)in blood and gastric,jejunum,and colon tissues were determined by ELISA,the mRNA and protein expression of norepinephrine transporter(NET)in the gastric,jejunum,and colon tissues were respectively detected by RT-PCR and Western blot,and the positive expression of the α_(1),α_(2),β_(1),β_(2)-type adrenergic receptor in the gastric,jejunal,and colonic tissues were detected by immunohistochemistry.Results The gastric emptying rate and small intestinal propulsion rate of rat s in the model group were significantly lower than those in the control group(all P<0.05),while the rates in the HSD group andα-receptor inhibit
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