四神丸对IBS-D模型大鼠脑肠组织Ghrelin及其受体GHSR阳性表达的影响  

Effect of Sishen Pill on Positive Expressions of Ghrelin and Its Receptor GHSR in Cerebral Intestinal Tissue of IBS-D Model Rats

作　　者：蔺晓源[1] 邓娜[2] 夏旭婷 刘富林[2] LIN Xiaoyuan;DENG Na;XIA Xuting;LIU Fulin(The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China;Hunan University of Chinese Medicine, Changsha 410208, China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南中医药大学,湖南长沙410208

出　　处：《中医药学报》2022年第4期17-22,共6页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金项目(81403380);湖南省自然科学基金项目(2020JJ5432);湖南省教育厅科学研究青年项目(21B0368);湖南省卫生健康委科研课题(20200541);湖南中医药大学中医学国内一流建设学科开放基金(2021ZYX15)。

摘　　要：目的:探讨四神丸对腹泻型肠易激综合征(IBS-D)模型大鼠下丘脑、十二指肠组织中脑肠肽胃促生长素(Ghrelin)及其受体GHSR阳性表达的影响。方法:将60只SD大鼠随机分为正常组(10只)和造模组(50只),采用番泻叶灌胃加避水应激法复制IBS-D大鼠模型,待造模成功后再将模型大鼠随机分为模型组、得舒特组及四神丸高、中、低剂量组(每组10只);得舒特组给予临床等效剂量的得舒特药液,四神丸各组灌胃给予等效剂量4、2、1倍的四神丸药液,连续14 d;给药前后观察各组大鼠的排便和肠道动力情况,运用免疫组化法检测各组大鼠下丘脑、十二指肠中Ghrelin、GHSR的蛋白阳性表达。结果:给药后与正常组比较,模型组大鼠的稀便率升高(P<0.01)、玻璃小球排出时间减少(P<0.01),与模型组比较,各给药组的稀便率均明显下降(P<0.01)、玻璃小球排出时间均明显增加(P<0.01),且稀便率以四神丸高剂量组下降最为明显(P<0.01);模型组大鼠下丘脑、十二指肠中Ghrelin、GHSR的阳性表达均明显高于正常组(P<0.01);与模型组比较,各给药组下丘脑中Ghrelin、GHSR的阳性表达均减少(P<0.01),且四神丸高剂量组的Ghrelin表达低于低剂量组(P<0.05);各给药组十二指肠中Ghrelin的阳性表达均减少(P<0.05,P<0.01),且四神丸高剂量组和得舒特组低于低剂量组(P<0.05);四神丸高、中剂量组和得舒特组十二指肠中GHSR阳性均表达减少(P<0.05),且其低于低剂量组(P<0.05)。结论:四神丸治疗IBS-D的作用可能与调节Ghrelin及其受体在脑肠互动中的表达有关。Objective:To explore the effect of Sishen Pill on positive expression of brain-gut peptide Ghrelin and its receptor GHSR in hypothalamus and duodenal tissues in model rats with diarrhea predominant irritable bowel syndrome(IBS-D).Methods:60 SD rats were randomly divided into the normal group(n=10)and the modeling group(n=50).The IBS-D rat model was replicated by folium sennae gavage and water stress avoidance.The successful modeling was randomly divided into the model group,the Dicetel group and the Sishen Pill groups of high-dose,medium-dose and low-dose,with 10 rats in each group.The Dicetel group was given a clinically equivalent dose of Dicetel solution,and Sishen Pill groups were give a clinical equivalent dose of 4,2 and 1 times of Sishen Pill solution for 14 d continuously.The defecation and intestinal motility of each group were observed before and after the treatment.The positive protein expressions of Ghrelin and GHSR in hypothalamus and duodenum were detected by immunohistochemistry.Results:Compared with those in the normal group,loose stools rate increased(P<0.01),and glass small ball discharge time reduced in the model group(P<0.01).Compared with those in the model group,the loose stools rate decreased significantly(P<0.01),the glass small ball discharge time increased significantly(P<0.01),and the loose stools rate was most significantly decreased in the high-dose group(P<0.01).The positive expressions of Ghrelin and GHSR of hypothalamus and duodenum were significantly higher in the model group than those in the normal group(P<0.01).Compared with those in model group,the positive expressions of Ghrelin and GHSR in hypothalamus were reduced in all medication groups(P<0.01);the expression of Ghrelin was lower in the high-dose group than that in the low-dose group(P<0.05);the positive expression of Ghrelin in duodenum was reduced in all medication groups after the treatment(P<0.05,P<0.01),and the high-dose group and the Dicetel group were lower than the low-dose group(P<0.05);the positive expression of

关 键 词：腹泻型肠易激综合征 四神丸 胃促生长素 胃促生长素受体 

分 类 号：R285.5[医药卫生—中药学]