肠三叶因子对新生大鼠坏死性小肠结肠炎的保护作用(英文)

Protective effects of intestinal trefoil factor on neonatal rats with necrotizing enterocoli

摘要:

目的 肠三叶因子(ITF)对消化道粘膜上皮细胞的损伤修复具有重要作用。本实验通过研究ITF 对新生大鼠坏死性小肠结肠炎(NEC)模型肠组织病理学改变,环氧合酶 2(COX 2)表达及前列腺素E2(PGE2)、血 栓素B2(TXB2)生成的影响,以探讨ITF对NEC是否有治疗作用。方法 40只新生1日龄Wistar大鼠随机分为5 组,每组8只。A组为正常对照组。B和C组大鼠为NEC模型鼠,分别予以0.5mL生理盐水腹腔或0.2mL皮下注 射。D和E组大鼠亦为NEC模型鼠,分别予以0.5mLITF(0.5mg)腹腔或0.2mL(0.2mg)皮下注射。连续3天 新生大鼠予以缺氧-复氧处理制成NEC模型。第4天处死所有大鼠,取肠组织检查组织病理学改变,COX 2表达 和PGE2与TXB2的生成。结果 A组的肠组织病理学未见异常,病理评分为0分。与相应的NEC组(B和C组) 比较,ITF治疗后(D和E组)NEC导致的组织病理学改变明显减轻(P<0.01)。B和C组的病理学评分为1～4 分,而D和E组评分为0～2分。与A组比较,B和C组PGE2与TXB2浓度显著增高,但ITF治疗后(D和E组)显 著下降,与A组无明显差异。免疫组化结果显示B和C组的COX 2表达显著高于A,D,E组(P<0.05)。D和E 组弱表达COX 2,其强度高于A组,但显著低于B和C组。结论 ITF通过抑制COX 2的表达,减少了PGE2和 TXB2含量,减轻肠组织炎

Abstract:

Objective The intestinal trefoil factor (ITF) is closely related with gastrointestinal epithelial cells injury repair. Studying the effects of ITF on necrotizing enterocolitis (NEC) would be helpful to the treatment of NEC. This research investigated the effect of ITF on intestinal histopathological changes, expression of cyclooxygenase-2 (COX-2 ) and the production of prostaglandin E 2 (PGE 2 )and thromboxane B 2 (TXB 2) in neonatal rats with NEC.Methods Forty one-day-old Wistar rats were randomly divided into 5 groups: Groups A, B, C, D and E (n=8 each). Group A served as the normal control group. Rats in Groups B, C, D and D were made into NEC models by hypoxia and re-oxygenation for 3 consecutive days. Groups D and E were treated with 0.5 mL ITF ( 0.5 mg) intraperitoneal injection or 0.2 mL ITF ( 0.2 mg) subcutaneous injection once respectively after damage, while Groups B and E were injected with normal saline intraperitoneally or subcutaneously respectively. On the 4th day all the subjects were sacrificed and intestinal tissues were obtained to examine the histological changes, COX-2 expression, and PGE 2 and TXB 2 productions. Results Intestinal histopathology of rats in Group A was normal, and the pathologic scores were 0. As compared with the corresponding NEC group(Groups B and C), histopathological injuries of NEC were remarkably relieved after ITF treatment (Groups D and E)(P < 0.01). The pathologic scores of rats in Groups B and C were 1- 4, while those of Groups D and E were 0-2. PGE 2 and TXB 2 contents significantly increased in Groups B and C, while dramatically decreased after ITF treatment (in Groups D and E). No significant differences were observed for the PGE 2 and TXB 2 contents between Groups D, E and A. Immunohistochemistry staining indicated positive expression of COX-2 in Groups B and C, which were significantly higher than Groups A, D and E (P < 0.05). Mild positive expression of COX-2 was observed in Groups D and E, which was stronger than Group A. Conclusions ITF can decrease the productions of PGE 2 and TXB 2 by suppressing the expression of COX-2, which may be underlying protective mechanisms of ITF on NEC.