【摘要】 目的观察痛泻要方破壁饮片对慢性避水应激大鼠内脏高敏感性的调节作用。方法将85只Wistar大鼠随机分为空白组、模型组、匹维溴铵组(0.018 g·kg^-1)、痛泻要方传统饮片组(4.060 g·kg^-1)及痛泻要方破壁饮片低、中、高剂量组(1.015、2.030、4.060 g·kg^-1)。采用慢性避水应激法建立肠易激综合征内脏高敏感性大鼠模型,连续10 d。第3天开始,每日避水实验前1 h进行灌胃给药,连续8 d。观察记录模型复制期间大鼠体质量及排便情况;采用腹壁撤回反射（AWR）评分对大鼠进行内脏敏感性评估;观察5-羟色胺（5-HT）诱导下大鼠离体肠平滑肌收缩情况;采用ELISA法检测大鼠结肠及脑组织中的5-HT含量;苏木精-伊红染色法（HE）观察大鼠结肠及脑组织病理形态学变化;采用免疫组化及Western Blot法检测5-羟色胺3A受体（5-HTR3A）在大鼠结肠黏膜及脑组织中的表达情况。结果与空白组比较,模型组大鼠体质量明显下降（P<0.01）,排便粒数及AWR评分明显增加（P<0.01）;5-HT诱导的大鼠离体结肠肌条张力显著增加（P<0.01）;结肠黏膜及脑组织中的5-HT及5-HTR3A表达量显著增加（P<0.01）。与模型组比较,痛泻要方破壁饮片各剂量组及传统饮片组的大鼠体质量呈明显上升趋势（P<0.05,P<0.01）,排便粒数明显减少（P<0.01）,痛泻要方破壁饮片高剂量组及传统饮片组的大鼠AWR评分明显降低（P<0.05,P<0.01）;痛泻要方破壁饮片组及传统饮片组的离体结肠肌条张力明显降低（P<0.05,P<0.01）;痛泻要方破壁饮片各剂量组及传统饮片组的大鼠结肠及脑组织中5-HT含量及5-HTR3A表达量均明显降低（P<0.05,P<0.01）。痛泻要方破壁饮片高剂量组的改善效果优于传统饮片组,但差异无统计学意义（P>0.05）。结论痛泻要方破壁饮片可有效缓解慢性避水应激大鼠的内脏高敏感性,其作用机制可能与调控5-HT信号通路,抑制5-HT及5-HTR3A的过度表达有关。更多还原

【Abstract】 Objective To study the effects of Tongxie Yaofang formula ultrafine granular powder（POTXYF）on the regulation of 5-HT signaling pathway in viscera hypersensitive of rats with chronic water avoidance stress（WAS）.Methods85 Wistar rats were randomly divided into normal group, model group, Pinaverium Bromide group(0.018 g·kg^-1),POTXYF low,medium,high dosages groups(1.015,2.030,4.060 g·kg^-1),and TXYF group(4.060 g·kg^-1). The visceral hypersensitive model（VH）of diarrheal irritable bowel syndrome（IBS-D）in rats were established by WAS for 10 d. From the third day of modelling,the rats were given correspondent drugs 1 h before WAS consecutively for 8 d. The changes of body mass, number of fecal pellets and abdominal withdrawal reflex（AWR）scores in VH rats were measured and evaluate. The contractility of colon smooth muscle induced by 5-HT in vitro was observed. The concentrations of 5-HT in the colon and brain were determined by ELISA. The pathological structure of the colonic mucosa and brain was visualized by HE. The expression of 5-HTR3 A in colonic mucosa and brain was determined by IHC and Western Blot.ResultsCompared with the normal group,the body mass in model group rats were decreased significantly（P<0.01）;the number of fecal pellets and the AWR score were increased significantly（P<0.01）;the contractility of colon smooth muscle increased significantly induced by 5-HT in vitro（P<0.01）;the pathological structure of the colonic mucosa and brain were slight changed,and the expressions of5-HT and 5-HTR3 A in the colonic mucosa and brain were significantly increased（P<0.01）. Compared with the model group,the body mass increased significantly in each treatment group（P<0.05,P<0.01）;the numbers of fecal pellets were decreased significantly（P<0.01）;and the AWR scores in POTXYF high dose group and TXYF group decreased significantly（P<0.05, P<0.01）. The hypervelocity contractility of colon smooth muscle were effectively inhibited significantly in POTXYF groups and TXYF group（P<0.05,P<0.01）,and the expression of5-HT and 5-HTR3 A in colon mucosa and brain effectively were reduced（P<0.05, P<0.01）. The effect of POTXYF high dose group was better than TXYF.ConclusionPOTXYF can treat IBS-D effectively, improvevisceral hypersensitivity in VH model rats; the mechanism may be related to inhibition of excessive release andsynthesis of 5-HT in the colon and brain by regulating the 5-HT signaling pathway.更多还原