吴门抑激散对腹泻型肠易激综合征大鼠肠道、下丘脑5-羟色胺信号传导系统的调控作用研究  

Regulatory effect of Wumen-Yiji powder on intestinal and hypothalamic serotonin signal transduction system in rats with diarrhea irritable bowel syndrome

作　　者：梁国强[1] 章一凡[2] 葛惠男[2] 朱慧[2] 欧阳八四[3] 朱惠萍[2] 杰辉[2] 郭金伟[2] 孙柳[3] 龚诚[2] 沈贤敏[2] 沈为濂 Liang Guoqiang;Zhang Yifan;Ge Huinan;Zhu Hui;Ouyang Basi;Zhu Huiping;Jie Hui;Guo Jinwei;Sun Liu;Gong Cheng;Shen Xianmin;Shen Weilian(Central Laboratory,Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine,Suzhou 215009,China;Department of Gastroenterology,Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine,Suzhou 215009,China;Suzhou Academy of Wumen Chinese Medicine,Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine,Suzhou 215009,China;Department ofInformation,Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine,Suzhou 215009,China)

机构地区：[1]南京中医药大学附属苏州市中医医院中心实验室,215009 [2]南京中医药大学附属苏州市中医医院脾胃病科,215009 [3]南京中医药大学附属苏州市中医医院苏州市吴门医派研究院,215009 [4]南京中医药大学附属苏州市中医医院信息科,215009

出　　处：《国际中医中药杂志》2021年第11期1089-1096,共8页International Journal of Traditional Chinese Medicine

基　　金：江苏省苏州市科技局基金项目(SYSD2018151);江苏省名老中医药专家葛惠男传承工作室建设项目(SZYK20191017);江苏省青年医学人才资助项目(QNRC2016252)。

摘　　要：目的:研究吴门抑激散对腹泻型肠易激综合征(IBS-D)模型大鼠肠道、下丘脑5-羟色胺(5-HT)信号传导系统的调控作用。方法:将60只SD雄性大鼠按随机数字表法分为空白组(10只)、腹泻型肠易激综合征组(50只),腹泻型肠易激综合征组经番泻叶灌胃+束缚应激2周后形成IBS-D模型,将其按随机数字表法分为模型组、得舒特组(1.5 mg/kg)、吴门抑激散低剂量组(6 g生药/kg)、吴门抑激散中剂量组(12 g生药/kg)和吴门抑激散高剂量组(24 g生药/kg),每组10只。连续给药2周后,采用ELISA法检测大鼠血清、结肠和下丘脑组织中5-HT含量;HE染色法观察各组大鼠结肠病理改变;采用Western blot法和RT-PCR法分别检测结肠和下丘脑组织中色氨酸羟化酶1(TPH-1)、5-羟色胺受体3(5-HT3R)、5-羟色胺受体4(5-HT4R)、5-羟色胺转运体(SERT)蛋白和mRNA水平。结果:与模型组比较,各给药组结肠病理形态有所改善;与模型组比较,吴门抑激散中、高剂量组大鼠血清、结肠5-HT水平降低(P<0.05),下丘脑5-HT水平升高(P<0.05);吴门抑激散中、高剂量组结肠TPH-1、5-HT3R、5-HT4R蛋白表达降低(P<0.05)、SERT蛋白表达升高(P<0.05);吴门抑激散高剂量组下丘脑TPH-1、5-HT3R、5-HT4R蛋白表达升高(P<0.05)、SERT蛋白表达降低(P<0.05);吴门抑激散低、中、高剂量组结肠TPH-1 mRNA[(4.778±0.604)、(3.278±0.668)、(1.670±0.361)比(6.877±0.148)]、5-HT3R mRNA[(3.807±0.463)、(2.697±0.455)、(1.132±0.136)比(6.322±0.778)]、5-HT4R mRNA[(4.521±0.234)、(2.801±0.351)、(1.331±0.142)比(6.741±0.293)]水平降低(P<0.05);吴门抑激散中、高剂量组下丘脑5-HT4R mRNA[(0.616±0.208)、(0.726±0.226)比(0.521±0.062)]水平升高(P<0.05),吴门抑激散高剂量组SERT mRNA[(1.563±1.023)比(2.612±1.035)]水平降低(P<0.05)。结论:吴门抑激散在一定剂量范围内可双向调节IBS-D大鼠结肠和下丘脑组织中5-HT信号传导系统相关蛋白和mRNA表达,从而改善IBS-D症状。Objective:To study the regulatory effect of Wumen-Yiji powder on 5-hydroxytryptamine(5-HT)signal transduction system in intestine and hypothalamus of diarrhea irritable bowel syndrome(IBS-D)model rats.Methods:Sixty male SD rats were randomly divided into blank group(10 rats)and diarrhea irritable bowel syndrome group(50 rats).The diarrhea irritable bowel syndrome group formed the diarrhea irritable bowel syndrome model after 2 weeks of senna leaf gavage and restraint stress.They were randomly divided into model group,deshute group(1.5 mg/kg),low,medium and high dose group of Wumen-Yiji San(6,12,24 g/kg),with 10 rats in each group.After continuous administration for 2 weeks,the contents of 5-HT in serum,colon and hypothalamus were detected by ELISA;HE staining was used to observe the pathological changes of colon in each group.The protein and mRNA levels of tryptophan hydroxylase 1(TPH-1),serotonin receptor 3(5-HT3R),serotonin receptor 4(5-HT4R),serotonin transporter(SERT)in colon and hypothalamus were detected by Western blot and RT-PCR,respectively.Results:Compared with the model group,the pathological morphology of colon in each treatment group was improved.Compared with the model group,the level of 5-HT in serum and colon significantly decreased(P<0.05),and the level of 5-HT in hypothalamus of rats in the low,medium,high dose group of Wumen-Yiji San significantly increased(P<0.05).The expression of TPH-1,5-HT3R and 5-HT4R protein significantly decreased(P<0.05),and the expression of SERT protein in the medium,high dose group of Wumen-Yiji San significantly increased(P<0.05).The expression of TPH-1,5-HT3R and 5-HT4R protein in hypothalamus increased(P<0.05),and the expression of SERT protein in the high dose group of Wumen-Yiji San significantly decreased(P<0.05).The mRNA levels of TPH-1(4.778±0.604,3.278±0.668,1.670±0.361 vs.6.877±0.148),5-HT3R(3.807±0.463,2.697±0.455,1.132±0.136 vs.6.322±0.778),5-HT4R(4.521±0.234,2.801±0.351,1.331±0.142 vs.6.741±0.293)in colon tissue of low,medium and high dose gr

关 键 词：肠易激综合征 吴门抑激散 5-HT信号传导系统 大鼠 

分 类 号：R285.5[医药卫生—中药学]