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目的探讨金荞麦醇提取物(FAE)干预腹泻型肠易激综合征(D-IBS)模型大鼠及离体结肠肠管运动功能作用及机制。方法用新生期乳大鼠母源性分离(NMS)联合醋酸(AA)灌肠法制作D-IBS模型,动物随机分为干预前对照组(10只,不灌胃)、对照盐水组(8只,生理盐水灌胃)、干预前模型组(10只,不灌胃)、模型盐水组(8只,生理盐水灌胃)、FAE 6 g/kg组(8只,FAE灌胃)、FAE 24 g/kg组(8只,FAE灌胃),匹维溴铵组(8只,0.02 g/kg灌胃),灌胃每天1次,共2周。用腹壁撤退反射(AWR)评估结肠高敏感性变化,用Bristol大便性状评分评估大鼠粪便稀便级并计算其粪便湿重。同时体外观察了不同浓度FAE和匹维溴铵(0.02μg/m L)对大鼠离体结肠自发收缩、乙酰胆碱(Ach)引发的痉挛性收缩以及对肠内Ca2+通道的作用。结果与干预前对照组比较,干预前模型组痛觉压力阈值及最大耐受压力值明显降低(P<0.05),粪便稀便级及粪便湿重明显增高(P<0.01);与对照盐水组比较,模型盐水组痛觉压力阈值及最大耐受压力值明显降低(P<0.05),粪便稀便级及粪便湿重明显增高(P<0.01);与模型盐水组比较,FAE24 g/kg组及匹维溴铵组痛觉压力阈值均明显升高(P<0.05)。FAE6 g/kg组粪便湿重、FAE24 g/kg组与匹维溴铵组粪便稀便级及粪便湿重均明显下降(P<0.05)。FAE(30、100、300、1 000、3 000μg/m L)及匹维溴铵对肠管自发收缩均有显著的抑制效应(P<0.05,P<0.01),且FAE(30,100,300×10-6g/m L)对Ach引发的痉挛性收缩及Ca Cl2促发的张力性收缩均有剂量依赖地松弛作用(P<0.05,P<0.01),匹维溴铵亦能显著抑制Ach及Ca Cl2引发的收缩作用(P<0.01)。结论 FAE有效成分可能通过Ca2+通道竞争拮抗作用,剂量依赖地抑制结肠运动亢进,进而参与改善IBS模型的排便功能及肠痉挛引起的痛觉过敏。
Objective To investigate the effect and mechanism of Fagor Albus alcohol extract (FAE) on colonic motility in rats with diarrhea-predominant irritable bowel syndrome (D-IBS). Methods D-IBS model was made by maternal neonatal isolation (NMS) and acetic acid (AA) enema in neonatal rats. Animals were randomly divided into control group (n = 10), control group , Normal saline (n = 10), model group (n = 10, model group), model group (n = 8, saline group), FAE 6 g / g / kg group (8 rats, FAE intragastric administration) and piroxicam group (8 rats, 0.02 g / kg intragastric administration) were given once daily for 2 weeks. Colonic hypersensitivity changes were evaluated by abdominal wall reflex (AWR), stool stool score was used to assess stool loose stools, and stool wet weight was calculated. At the same time, spontaneous contractions of isolated colon, acetylcholine (Ach) -induced spasmodic contraction and intestinal Ca2 + channels were observed in vitro by different concentrations of FAE and pinaverium bromide (0.02 μg / mL). Results Compared with the control group before intervention, the values of maxillary pressure and maximal pressure were significantly decreased (P <0.05), stool loose stool weight and stool wet weight significantly increased (P <0.01), compared with the control saline group (P <0.05), the fecal excrement level and stool wet weight increased significantly (P <0.01). Compared with the model saline group, FAE24 g / kg group and the control group The thresholds of pain pressure were significantly increased in the verapamil group (P <0.05). FAE6 g / kg group feces wet weight, FAE24 g / kg group and pinavirin group stool loose stool weight and stool wet weight were significantly decreased (P <0.05). FAE (30,100,300,1 000,3 000μg / m L) and pinaverium bromide had significant inhibitory effect on spontaneous contraction of intestine (P <0.05, P <0.01), and FAE (30,100,300 × 10-6g / m L) had a dose-dependent relaxation effect on spasmodic contraction induced by Ach and tension contraction induced by CaCl 2 (P <0.05, P <0.01), and pivaloyl bromide also significantly inhibited Ach and CaCl 2 -induced (P <0.01). CONCLUSION: The active ingredients of FAE may compete with Ca2 + channels for antagonism and inhibit colonic hypersensitivity in a dose-dependent manner, thereby further improving bowel function and bowel spasm-induced hyperalgesia in IBS model.