八面蒙脱石灌肠对重症急性胰腺炎大鼠结肠屏障的保护作用

The role of octabedral montone in colonic barrier protection in severe acute pancreatitis rat model

目的探讨八面蒙脱石是否在急性胰腺炎有保护结肠屏障的作用及可能的机制。方法72只雄性SD大鼠按完全随机法分为假手术组（SO组）、重症急性胰腺炎模型组（SAP组）、八面蒙脱石灌肠干预组（干预组），每组24只。采用胰胆管内逆行注射法诱导大鼠急性胰腺炎模型；SO组开腹注射生理盐水后关腹；干预组于造模前0．5h行八面蒙脱石液灌肠（1ml／100g）。术后分别于3、6、12h取胰腺组织行病理学评分，并测定血清TNFα、血浆二胺氧化酶和内毒素水平，取结肠组织以RT-PCR法及Westernblot法检测结肠黏膜细胞问紧密连接蛋白Occludin及其mRNA的表达。结果（1）光镜下SAP组可见胰腺组织炎性细胞浸润、出血和腺泡坏死，于预组病变相对较轻，SO组为正常胰腺表现。（2）血清TNFα水平在SAP组最高，与其他两组的差别有统计学意义（P〈0．05），干预组较SAP组降低（P〈0．05）。（3）SAP组各时间点的血内毒素和二胺氧化酶水平明显较SO组升高（P值均〈0．01），而于预组则较SAP组降低（P〈0．01）；Occludin的蛋白及mRNA表达水平在SAP组明显减少（P〈0．01），而干预组较之有所改善（P〈0．01）。结论八面蒙脱石有助于维持SAP大鼠结肠屏障结构和功能，从而降低内毒素血症，改善炎症造成的组织损伤，对大鼠急性胰腺炎有保护作用。

Objective To investigate the protective mechanism of oetahedral montone in rats with acute pancreatitis. Methods Seventy-two SD rats were randomly divided into a sham-operation （SO） group, a severe acute pancreatitis （SAP） group and a treatment with octahedral montone group. Retrograde pancreatic duetal injection of 5% cholate sodium in rats was used to establish SAP models. Sham operation was done with intraperitoncal injection of normal saline. In the treated group octahedral montone was given through enema half hour before inducing SAP model. Then,we evaluate the pancreatic injury and detect the level of TNF-αlpha, diamine oxidase （DAO） and endotoxin. Western blot and RT-PCR were used to determine the expressions of the tight junction protein occludin in the endothelial cells of intestinal mucosa at the time of hour 3,6, 12 after operation. Results （ 1 ） The pathological scores of panereatitis were significantly higher in the SAP group than those in the treatment group and SO group （ P 〈 0. 05 ）. （ 2 ） Compared with the SO group, the level of TNF-αlpha in the SAP group and the treatment group was much higher （P 〈 0. 05） ,but the level in the treatment group was lower than that in the SAP group （ P 〈 0. 05）. （3） The serum concentration of DAO and endotoxin was significantly increased in the SAP group, and the concentration in treatment group was higher than that in the SO group（P 〈0. 01 ）, but lower than that in the SAP group（ P 〈0. 01 ）. The occludin protein and mRNA expression in the SAP group was the lowest and the expression in the treatment group was higher than that in the SAP group （P 〈 0. 01 ）, but lower than that in the SO group （ P 〈 0. 01 ）. Conclusions Octahedral montone can improve the colonic barrier function, reduce the endotoxemia, and ameliorate the inflammation during acute pancreatitis.