盐酸小檗碱对肠易激综合征大鼠肠上皮紧密连接的影响

目的：观察盐酸小檗碱( Berberine, BER)对肠易激综合征( IBS)大鼠肠上皮紧密连接的影响,探讨其机制。方法将50只SD大鼠随机分为5组,每组10只。除对照组正常进食水外,其他4组采用醋酸灌肠法建立IBS模型,造模成功后予如下方法处理：BER 组予盐酸 BER (100 mg/kg )灌胃；氨基胍组予高度选择性一氧化氮合酶(NOs)阻断剂氨基胍(100 mg/kg)腹腔注射；BER+氨基胍组予BER(100 mg/kg)灌胃,同时氨基胍(100 mg/kg)腹腔注射；生理盐水组予3 ml 生理盐水灌胃。造模后第7天比较5组大鼠腹部回撤反应( abnominal withdrawl reflex, AWR)评分(直结肠扩张试验)、束缚应激试验后排便次数、血浆D-乳酸水平、肠上皮紧密连接( tight junction, TJ)蛋白(Occludin、ZO-1)的表达。结果与对照组比较,BER组、BER+氨基胍组、氨基胍组、生理盐水组4组AWR评分升高,束缚应激后排便增多,D-乳酸水平升高,肠上皮TJ蛋白Occludin、ZO-1表达下降,差异有统计学意义( P<0．05)。BER组AWR评分比生理盐水组明显降低(P<0．05),氨基胍组、BER+氨基胍组AWR评分与生理盐水组比较,差异无统计学意义(P>0．05),BER组AWR评分比BER+氨基胍组明显降低(P<0．05)；与生理盐水组比较,BER组和BER+氨基胍组排便次数减少, D-乳酸水平降低,肠上皮蛋白；Occludin、ZO-1表达升高,差异有统计学意义( P <0．05)。排便次数、D-乳酸水平、肠上皮TJ蛋白Occludin与ZO-1表达比较氨基胍组与生理盐水组差异均无统计学意义(P>0．05)。结论 BER影响IBS大鼠肠上皮紧密连接,其机制与一氧化氮有关。

Effect of Berberine on Intestinal Epithelium Tight Junction in Rats with Irritable Bowel Syndrome

Objective To observe the effect of Berberine ( BER) on intestinal epithelium tight junction ( TJ) in rats with irritable bowel syndrome ( IBS) and to investigate its mechanisms. Methods The 50 SD rats were randomly di-vided into five groups. The control group took food and water normally (n=10), and IBS rat models were established by the acetic-acid clyster in other 4 groups. After successful model establishment, BER group was lavaged with BER solution (100 mg/kg, n=10);Aminoguanidine group was given intraperitoneal injection with Aminoguanidine (100 mg/kg, n=10), which was a kind of blocking agent to nitric-oxide synthase (NOs);BER+Aminoguanidine group was treated with BER solution intragastric administration ( 100 mg/kg ) and simultaneous Aminoguanidine intraperitoneal injection (100 mg/kg, n=10);saline group was lavaged with 3 ml physiological saline (n=10). Values of abdominal withdraw-al reflex ( AWR) score, defecation frequency after restraint stress procedure, the plasma D-lactate level and expressions of TJ (Occludin and ZO-1) were compared in the five groups 7 d after model establishment. Results Compared with those in control group, the AWR scores, defecation frequency after restraint stress procedure and the plasma D-lactate level were significantly increased, while the expressions of TJ (Occludin and ZO-1) were significantly decreased in BER, Aminoguanidine, BER +Aminoguanidine and saline groups ( P <0. 05 ) . Compared with that in saline group, AWR score in BER group was significantly decreased (P<0. 05), but the scores showed no statistically significant differences between Aminoguanidine and BER+Aminoguanidine groups (P>0. 05). AWR score in BER group was significantly de-creased compared with that in BER+Aminoguanidine group (P<0. 05). Compared with those in saline group, the defe-cation frequency and plasma D-lactate level were significantly decreased, while the expressions of TJ Occludin and ZO-1 were significantly increased in BER and BER+Aminoguanidine groups ( P<0. 05 ) . There were no significant differ-ences in defecation frequency, the plasma D-lactate level and expressions of TJ Occludin and ZO-1 between Aminoguani-dine and saline groups (P>0. 05). Conclusion BER may affect intestinal epithelium tight junction in IBS rats, and its mechanism are related to nitric oxide.