摘要
目的 探讨碱性成纤维细胞生长因子 (bFGF)对大鼠缺血性损伤的保护作用及其分子机制。方法 利用肠系膜上动脉夹闭 (SMA) 4 5min后松夹造成缺血再灌注 (I/R)损伤作为动物模型。将 78只Wistar大鼠随机分为假手术组 (A组 )、生理盐水对照治疗组 (B组 )、bFGF抗体预处理组 (C组 )和bFGF治疗组 (D组 )。A组分离SMA但不夹闭 ,45min后活杀动物 ,其余各组分别于松夹后 2、6、2 4和 48h活杀动物 ,取血浆检测二氨氧化酶 (DAO)含量 ,取小肠组织利用免疫组织化学技术检测磷酸化 p38钙调蛋白依赖性蛋白激酶 (MAPK)及SAPK/JNK的活性 ,并行苏木素 伊红(HE)染色于光镜下观察病理形态学改变。结果 HE染色结果显示 ,I/R损伤后 6h肠屏障功能损伤最严重 ,D组在再灌注 48h损伤较B组及C组减轻。损伤后 6h ,D组DAO含量 (2 .55± 1 .2 2 )低于C组 (2 .86± 0 .94) (P <0 .0 5)。p38MAPK及SAPK/JNK在正常小肠组织表达极少 ,I/R损伤后表达量增高。p38MAPK染色主要位于小肠隐窝 ,少量存在于绒毛尖处。B组及C组磷酸化 p38MAPK在 6h表达量达高峰 ,而D组在 2h达高峰。SAPK/JNK在各组表达均呈弱阳性 ,于再灌注后 2 4h表达量达峰值 ,组间无明显区别。结论 外源性bFGF对肠I/R损伤有保护作用 ,其保护机制可能与损伤早期激活p38MAPK信号?
Objective To investigate the effect of extrogenous basic fibroblast growth factor (bFGF) on rat intestinal ischemia/reperfusion injury and the activities of p38 MAPK and SAPK/JNK signaling pathway, and to explore the protective mechanism of extrogenous bFGF on gut ischemis/reperfusion (I/R) injury.Methods Rat intestinal I/R injury produced by clamping the superior mesenteric artery (SMA) for 45?min followed by reperfusion was used as animal model. Seventy eight Wistar rats were divided randomly into sham operation group (A), normal saline control group (B), bFGF antibody pretreated group (C) and bFGF treated group (D). In group A, SMA were separated but without occlusion. Animals were sacrificed, blood and tissue samples from intestine were taken at 45 min after ischemia in group A and 2, 6, 24 and 48?h after the reperfusion in the other groups. DAO levels were measured and phosphorylated forms of p38 MAPK and SAPK/JNK were detected. The histological changes were observed under the light microscope.Results The intestinal barrier was damaged seriously 6 h after reperfusion examined by HE staining. However, the improvement of histological structures was observed 48?h after the reperfusion in group D as compared to other groups. DAO levels were decreased 6?h after reperfusion in group D (2.55±1.22) as compared with those in group C (2.86±0.94) (P< 0.05). Gut I/R injury stimulated the activities of p38 MAPK and SAPK/JNK signaling pathways. Phosphorylated forms of p38 MAPK was localized mainly in the nucleus of the crypt cells, very few in the villus cells. p38 MAPK expression peaked at 6?h after the reperfusion in groups B and C, 2 h in group D. SAPK/JNK activities peaked 24?h after the reperfusion, but the positive expressions were very weak at all the time points, and the expression level had no significant difference among the groups.Conclusion bFGF has a protective effect on intestinal I/R injury. The protective effect may be mediated by early stimulation of p38 MAPK signaling pathway.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2002年第5期426-428,共3页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金资助项目( 3990 0 0 54 )
全军医学科研"十五"计划面上项目 ( 0 1M2 11)
