首页|四神丸对肠易激合并抑郁模型大鼠的作用与机制研究

四神丸对肠易激合并抑郁模型大鼠的作用与机制研究

扫码查看
目的 探讨四神丸对肠易激综合征合并抑郁模型大鼠的改善作用及机制.方法 SD雄性大鼠随机分为正常组、模型组、盐酸氟西汀组和四神丸低、中、高剂量组.采用番泻叶灌胃联合慢性不可预知温和刺激建立模型,腹壁撤退反射、粪便含水量测定及糖水偏好实验检验模型.模型复制成功后给药14 d,给药结束后检测大鼠肠道敏感性和粪便含水量,并进行糖水偏好、旷场及强迫游泳实验,HE染色法观察海马和结肠病理结构变化,ELISA法测定大鼠海马 5-羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)、去甲肾上腺素(norepinephrine,NE)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平和结肠及血清内 5-HT含量.结果 与正常组比较,模型组大鼠海马和结肠形态结构损伤并伴有炎性细胞浸润,糖水偏好率和自主活动明显降低(P<0.01),肠道敏感性、稀便率和强迫游泳不动时间明显增加(P<0.01),海马组织中 5-HT、DA、NE、BDNF含量明显降低(P<0.01),血清和结肠 5-HT含量明显升高(P<0.01).与模型组比较,四神丸各剂量组及盐酸氟西汀组大鼠上述指标均有不同程度改善,其中四神丸高剂量组大鼠海马和结肠形态结构损伤修复,无炎性细胞浸润,糖水偏好率和自主活动明显增加(P<0.05),肠道敏感性,稀便率和强迫游泳不动时间明显下降(P<0.01);海马组织中 5-HT、DA、NE、BDNF含量明显升高(P<0.01);血清和结肠 5-HT含量明显降低(P<0.01).结论 四神丸具有改善肠易激综合征合并抑郁模型大鼠肠道症状及抑郁样行为的作用,可能与其调节海马内神经递质及血清和结肠5-HT水平、恢复肠道和中枢神经系统功能有关.
Study on the Effect and Mechanism of Sishen Pill on Irritable bowel syndrome Combined with Depression Model Rats
Objective To explore the effect of Sishen Pill on Irritable bowel syndrome combined with depression model rats.Methods SD male rats were randomly divided into normal group,model group,fluoxetine hydrochloride group and Sishen pill low-dose,medium-dose and high-dose groups.The model was established by giving sennae folium decoction combined with chronic unpredictable mild stress.Then the abdominal withdrawal reflex,fecal water content determination and sugar water preference test were used to verify the model.The drug was given for 14 days after the model was copied successfully.After administration,intestinal sensitivity and fecal water content of rats were detected,sugar water preference test,open field test and forced swimming test were performed.Pathological changes of hippocampus and colon were observed by HE staining.The levels of 5-hydroxytryptamine(5-HT),dopamine(DA),norepinephrine(NE),brain-derived neurotrophic factor(BDNF)in hippocampus,5-HT in blood and colon were measured by ELISA.Results Compared with the normal group,the morphological structure of hippocampus and colon in model group was damaged with inflammatory cell infiltration,and the preference rate of sugar water and locomotor activity were significantly decreased(P<0.01),while the intestinal sensitivity,fecal water content and immobility time of forced swimming were significantly increased(P<0.01),and the contents of 5-HT,DA,NE and BDNF in hippocampus were significantly decreased(P<0.01),while 5-HT contents in blood and colon increased(P<0.01).Compared with the model group rats,all the above indexes were improved to some extent in the rats in each dose group of Sishen pill and fluoxetine hydrochloride group.Morphological structural damage of hippocampus and colon in high dose group of Sishen pill was repaired,no inflammatory cell infiltration was observed.The preference rate of sugar water and locomotor activity were significantly increased(P<0.05),the intestinal sensitivity,fecal water content and immobility time of forced swimming were significantly decreased(P<0.01)in the Sishen pill high-dose groups.The contents of 5-HT,DA,NE and BDNF in hippocampus increased significantly(P<0.01),while the content of 5-HT in blood and colon decreased significantly(P<0.01)in the Sishen pill high-dose groups.Conclusion Sishen pill can improve the intestinal symptoms and depressive-like behaviors in irritable bowel syndrome combined with depression model rats,which may be related to the regulation of hippocampal neurotransmitters,serum and colon 5-HT levels,and the recovery of intestinal and central nervous system functions.

Sishen pillDiarrhea-irritable bowel syndromeDepressionBehaviorsNeurotransmitter

王桂群、许二平、刘雅琳、代丽萍、崔瑛、李玲玲、杨秋琛、李少玉

展开 >

河南中医药大学豫药全产业链研发河南省协同创新中心,郑州 450046

河南中医药大学中医药科学院,郑州 450046

河南中医药大学药学院,郑州 450046

四神丸 腹泻型肠易激综合征 抑郁症 行为学 神经递质

国家自然科学基金河南省重点研发与推广专项

82274496202102311090

2024

中国中医基础医学杂志
中国中医研究院基础理论研究所

中国中医基础医学杂志

CSTPCD
影响因子:0.779
ISSN:1006-3250
年,卷(期):2024.30(5)
  • 40