柳氮磺吡啶预防大鼠肠粘连形成效果的实验研究

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目的 探讨柳氮磺吡啶(SF)预防大鼠实验性肠粘连的效果及其机制.方法 将40只大鼠随机分为假手术组(Sham组)、空白对照组(BC组)、透明质酸钠(HA)组、低剂量SF组(LSF组)和高剂量SF组(LSF组),每组8只大鼠.除Sham组外,BC组、HA组、LSF组和HSF组大鼠均使用盲肠搔刮方法造立肠粘连模型.建模后BC组大鼠不予特殊处理,HA组大鼠的搔刮面涂抹2 mL HA,LSF组和HSF组术后每日分别给予50 mg/kg和100mg/kg SF灌胃,持续7d(其余4组大鼠予以生理盐水灌胃).于术后第7天,采用Nair's评分系统评价5组大鼠的腹部粘连情况;取粘连组织行HE染色观察粘连组织的病理学改变,并进行炎症程度评分及纤维形成评分;取粘连组织行免疫组织化学染色以检测α-平滑肌肌动蛋白(α-SMA)的表达,并对不同表达程度赋予相应分值;采用酶联免疫吸附实验检测大鼠血清中的白介素-1β(IL-1β)和转化生长因子-β1 (TGF-β1)浓度.结果 ①肠粘连情况:Sham组大鼠仅有3只大鼠发生切口粘连;BC组有4只大鼠发生切口粘连,8只大鼠发生腹壁与盲肠壁粘连,2只大鼠发生肠管与内脏的粘连;HA组有2只大鼠发生切口粘连,5只大鼠发生腹壁与盲肠壁粘连;LSF组有2只大鼠发生切口粘连,6只大鼠发生腹壁与盲肠壁粘连,1只大鼠发生肠管与内脏粘连;HSF组有2只大鼠发生切口粘连,4只大鼠发生腹壁与盲肠壁粘连.与Sham组比较,其余4组大鼠的肠粘连评分均较高(P<0.05);与BC组比较,HA组、LSF组和HSF组大鼠的肠粘连评分均较低(P<0.05),但HA组、LSF组和HSF组大鼠的肠粘连评分比较差异无统计学意义(P>0.05).②炎症程度评分和纤维形成评分:在炎症程度评分方面,与Sham组比较,其余4组大鼠的炎症程度评分均较高(P<0.05);与BC组比较,LSF组和HSF组大鼠的炎症程度评分均较低(P<0.05);与HA组比较,LSF组和HSF组大鼠的炎症程度评分均较低(P<0.05);与LSF组比较,HSF组大鼠的炎症程度评分的差异无统计学意义(P>0.05).在纤维形成评分方面:与Sham组比较,其余4组大鼠的纤维形成评分均较高(P<0.05);与BC组比较,HA组、LSF组和HSF组大鼠的纤维形成评分均较低(P<0.05),但HA组、LSF组和HSF组大鼠的纤维形成评分比较差异无统计学意义(P>0.05).③粘连组织中α-SMA的表达评分:与Sham组比较,其余4组大鼠的α-SMA表达评分均较高(P<0.05);与BC组比较,HA组、LSF组和HSF组大鼠的α-SMA表达评分均较低(P<0.05),但HA组、LSF组和HSF组大鼠的α-SMA表达评分比较差异无统计学意义(P>0.05).④血清中的IL-1β和TGF-β1浓度:在血清IL-1β浓度方面,与Sham组比较,其余4组大鼠血清中的IL-1β浓度均较高(P<0.05);与BC组比较,HA组、LSF组和HSF组大鼠血清中的IL-1β浓度均较低(P<0.05);与HA组比较,HSF组大鼠血清中的IL-1β浓度较低(P<0.05);与LSF组比较,HSF组大鼠血清中的IL-1β浓度较低(P<0.05).在血清TGF-β1浓度方面,与Sham组比较,其余4组大鼠血清中的TGF-β1浓度均较高(P<0.05);与BC组比较,HA组、LSF组和HSF组大鼠血清中的TGF-β1浓度均较低(P<0.05);与HA组比较,LSF组和HSF组大鼠血清中的TGF-β1浓度均较低(P<0.05);与LSF组比较,HSF组大鼠血清中的TGF-β1浓度的差异无统计学意义(P>0.05).结论 SF可通过减轻术后粘连组织中的炎症反应与纤维形成,有效减少大鼠动物模型中肠粘连的形成.“,”Objective To investigate the inhibition effect of salazosulfapyridine (SF) on the formation of post-operative abdominal adhesion and its possible mechanism.Methods Forty male Sprague-Dawley rats were randomly divided into five groups:sham operation group (Sham group),blank control group (BC group),sodium hyaluronate (HA) group,low dose of SF group (LSF group),and high dose of SF group (HSF group).Except the Sham group,all the rats in other 4 groups were created abdominal adhesion model by abrasion of caecum and its opposite abdominal wall.Rats of the BC group didn't received any treatment after model establishment.Before closing the abdominal wall,the rats of the HA group were treated by 2 mL HA.After the operation,the rats of the LSF group and the HSF group were daily orally administrated with different dose of SF (50 mg/kg for the LSF group and 100 mg/kg for the HSF group),while the other 3 groups treated with same dose of normal saline.Seven days after operation,the rats of 5 groups were killed and abdominal adhesion conditions was evaluated by Nair's score system.Then the abdominal adhesion tissues or blood were collected to underwent HE staining,immunohistochemistry staining,and enzyme linked immunosorbent assay (ELISA) test.The HE staining was used to assess the inflammation score and fibrillation score of rats in 5 groups and immunohistochemistry staining was used to evaluate expression of the u-smooth muscle actin (u-SMA) in adhesion tissues.The ELISA test was used to detect the concentration of serum interleukin-1 β (IL-1β) and transforming growth factor-β1 (TGF-β1) in rats of 5 groups.Results ① The gross evaluation of adhesion condition:3 rats of the Sham groups had incision adhesion;in the BC group,4 rats had incision adhesion,8 rats had cecum to the abdominal wall adhesion,2 rats had viscera to viscera adhesion;in the HA group,2 rats had incision adhesion and 5 rats had cecum to the abdominal wall adhesion;in the LSF group,2 rats had incision adhesion,6 rats had cecum to the abdominal wall adhesion,and 1 rat had viscera to viscera adhesion;in the HSF group,2 rats had incision adhesion and 4 rats had cecum to the abdominal wall adhesion.Compared with the Sham group,the Nair's scores of the other 4 groups were higher (P<0.05);compared with the BC group,the Nair's scores of the HA group,the LSF group,and the HSF group were all lower (P<0.05),but there was no significant difference on the Nair's scores among the HA group,the LSF group,and the HSF group (P>0.05).② Inflammation score and fibrillation score:on the inflammation score,compared with the Sham group,the inflammation scores of the others 4 groups were higher (P<0.05);compared with the BC and HA group,the inflammation scores of the LSF group and the HSF group were both lower (P<0.05);compared with the LSF group,there was no significant difference on the inflammation score of the HSF group (P>0.05).On the fibrillation score,compared with the Sham group,the fibrillation scores of the others 4 groups were higher (P<0.05);compared with the BC group,the fibrillation scores of the HA group,the LSF group,and the HSF group were all lower (P<0.05),but there was no significant difference on the fibrillation scores among the HA group,the LSF group,and the HSF group (P>0.05).③ The expression scores of u-SMA:compared with the Sham group,the expression scores ofu-SMA in the others 4 groups were higher (P<0.05);compared with the BC group,the expression scores of u-SMA in the HA group,the LSF group,and the HSF group were all lower (P<0.05),but there was no significant difference on the expression scores ofu-SMA among the HA group,the LSF group,and the HSF group (P>0.05).④ Concentration of serum IL-1β and TGF-β1:on the concentration of serum IL-1 β,compared with the Sham group,the concentrations of serum IL-1 β in the others 4 groups were higher (P<0.05);compared with the BC group,the concentrations of serum IL-1β in the HA group,the LSF group,and the HSF group were all lower (P<0.05);compared with the HA and the LSF group,the concentration of serum IL-1β in the HSF group was lower (P<0.05).On the concentration of serum TGF-β1,compared with the Sham group,the concentrations of serum TGF-β1 in the others 4 groups were higher (P<0.05);compared with the BC group,the concentrations of serum TGF-β1 in the HA group,the LSF group,and the HSF group were all lower (P<0.05);compared with the HA group,the concentrations of serum TGF-β1 in the LSF group and the HSF group were both lower (P<0.05),but there was no significant difference between the LSF group and the HSF group (P>0.05).Conclusion SF can reduce the formation of postoperative abdominal adhesion in rat models via inhibiting inflammation and fibrillation.
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