The Protective Effect Of Exogenous IGF-â…  On The Intestinal Mucosal Barrier In Rats With Severe Acute Pancreatitis

Objective The aim of this study is to demonstrate the protective effect of IGF-Ⅰon the intestinal mucosal barrier in rats with SAP and its possible mechanisms.Methods 72 male Wistar rats were randomly divided into 3 groups:sham operation(SO),SAP group(SAP)and IGF-Ⅰtreatment(IGF-Ⅰ)group.Every group was randomly divided into 3 time units(6,12,24h),8 rats in each time unit.SAP rats were induced by retrograde infusion of 5.0%sodium taurocholate into biliary-pancreatic duct,however,SO rats were infusioned NS by the same way.The rats in IGF-Ⅰgroup were inject IGF-Ⅰby subcutane at half an hour before operation and three hours after operation.Detect the serum amylase,Endotoxin and DAO, Pathological change of pancreas and the small intestine was observed.Apoptosis of mucosal cells was detected by TUNEL methods,the variation of the bax and bcl-2 gene expression in small intestine tissue was detected by reverse transcription polymerase chain reaction(RT-PCR).Results The rats of IGF-Ⅰgroup compared to the SAP group,the serum amylase(6h:2262.38±760.19 vs 3063.38±676.33;12h:1572.50±635.90 vs 2777.00±262.25;24h:1322.75±334.64 vs 2336.38±279.92)were lower than the corresponding time points,the difference were significantly at 12h and 24 h(P＜0.05). Endotoxin(6h:115.00±29.76 vs 77.75±28.49;2h:76.25±10.60vs 103.13±27.38;24h:53.75±10.61 vs147.50±16.69)in IGF-Ⅰgroup still higher than the SAP group at 6h,it is belower than the SAP group at 12h and 24h,but the difference has statistical significance at 24h(P＜0.05).Diamine oxidase(6h:2.39±0.53vs 0.99±0.50;12h:1.61±0.48 vs 1.94±0.42;24h:0.96±0.18 vs 2.81±0.80)have the same change compared with Endotoxin in two groups.In IGF-Ⅰgroup,the apoptosis index(6h:13.88±1.73 vs 19.00±2.78;12h:10.13±1.55 vs 17.63±1.60;24h:9.50±1.07 vs 17.25±2.76)of intestinal epithelial decreased significantly compared with SAP group(P＜0.05).the pathology score of small intestinal(6h:1.63±0.52 vs 2.38±1.06;12h:1.38±0.52 vs 2.88±0.99;4h:1.25±0.46 vs 2.75±0.71)was significantly reduced in IGF-Ⅰgroup.but the difference has statistical significance at 12h and 24h. Electron microscopic examination results also showed that pathological changes of the small intestine improved significantly in the IGF-Ⅰgroup,bax mRNA expression(6h:1.35±0.18vs 0.85±0.12;12h:1.21±0.21vs 0.86±0.24;24h: 1.14±0.24 vs 0.95±0.22)was increased significantly in the SAP group at each time point(P＜0.01)and tend to peak at 6 hrs post- injection,bax mRNA expression noticeably reduced in three time units of the IGF-Ⅰgroup(6h:1.10±0.23vs 1.35±0.18;12h:1.03±0.15 vs 1.21±0.21;24h:0.96±0.16 vs 1.14±0.24),It was nearly reached to level of the SO group expression at 24 hrs post-injection;bcl-2 mRNA expression was weak and have no difference between the SO group and SAP group(6h:0.54±0.04vs 0.57±0.06;12h:0.56±0.05 vs 0.53±0.05;24h:0.54±0.07 vs 0.58±0.08),but increased significantly in the IGF-Ⅰgroup(6h:0.65±0.07vs 0.54±0.04vs 0.57±0.06;12h:0.69±0.04vs 0.56±0.05 vs 0.53±0.05;24h:0.72±0.05vs 0.54±0.07 vs 0.58±0.08)at each time point(P＜0.05).The ratio of bax and bcl-2 mRNA(6h:.24±0.11vs 1.59±0.24;12h:2.10±0.20 vs 1.55±0.19;24h:2.06±0.21 vs 1.55±0.18)expression at each time point in the SAP group was significantly higher than that in the SO group,and decrease obviously in IGF-Ⅰgroup(6h:1.69±0.28vs 2.24±0.11;12h:1.41±0.19 vs 2.10±0.20;24h:1.21±0.23 vs 2.06±0.21).Conclusions:An increase in intestinal mucosal cell apoptosis is involved in the intestinal mucosal dysfunction of SAP rats.IGF-Ⅰcould decrease endotoxin translocation and alleviate intestinal epithelial cell apoptosis and protect the intestinal mucosal barrier function.It may be related to the mechanisms that IGF-Ⅰcould promote bcl-2 mRNA transcription and inhibit mRNA expression of bax mRNA...