急性出血坏死性胰腺炎大鼠肠道黏膜屏障功能变化及己酮可可碱对其的保护作用

目的 研究急性坏死性胰腺炎(ANP)大鼠肠道屏障功能改变及己酮可可碱(pentoxifylline,FTX)对肠道屏障的保护作用.方法 54只SD雄性大鼠按数字表法随机分为ANP组、PTX组和假手术组.采用逆行胰胆管注射5%牛磺胆酸钠建立ANP模型.假手术组只翻动十二指肠.PTX组在制模后经阴茎静脉注射PTX 25 mg/kg体重.术后3、6、24 h分批处死大鼠.取血测淀粉酶、D乳酸及TNF-α含量,取胰腺及末端回肠常规行病理学检查,免疫组化法检测回肠黏膜上皮紧密连接蛋白ZO-1的表达.结果 建模后6 h,ANP组血清淀粉酶、TNF-α、D-乳酸含量分别为(9141±672)U/L、(347.96±79.47)pg/ml和(10.21±1.08)mg/L,显著高于假手术组的(1723±57)U/L、(134.09±31.36)pg/ml和(4.33±0.49)mg/L(P值均＜0.01);PTX组血淀粉酶、TNF-α、D-乳酸分别为(7965±318)U/L、(238.48±44.35)pg/ml和(8.75±1.28)mg/L,较ANP组显著降低,但仍显著高于假手术组(P＜0.05或＜0.01).假手术组大鼠肠黏膜上皮ZO-1阳性率为(3.29±0.36)%;ANP组为(1.91±0.32)%,较假手术组明显减少(P＜0.05);PTX组为(2.53±0.43)%,较假手术组减少,但较ANP组明显增加(P＜0.05).结论 PTX可减轻ANP大鼠肠黏膜屏障功能的损伤,其机制可能是通过减少肠黏膜上皮ZO-1的降解.

Change of intestinal barrier function in acute necrotizing pancreatitis (ANP) rats and pentoxifylline's protective effects

Objective To investigate the change of intestinal barrier function and the protection of pentoxifylline (PTX) to intestinal barrier. Methods Fifty-four SD male rats were randomly divided into 3groups, including sham operation group, ANP group, PTX group. ANP rat model were induced by retrograde injection of 5% sodium taurocholate into pancreatic and bile duct. Rats in sham operation group underwent operation without injection of taurocholate. After ANP induction, the rats in PTX group received PTX at a dose of 25 mg/kg weight via penis vein. The rats were sacrificed 3, 6, 24 h after operation, the serum levels of amylase, D-lactic acid, TNF-α were determined. The pancreas tissue and terminal ileum were harvested for pathological examination; ZO-1 levels of ileum epithelial tight junction were analyzed by immunohistochemistry. Results Six hours after induction, the serum levels of amylase, TNF-α, D-lactic acid in ANP group were(9141±672)U/L, (347.96±79.47) pg/ml and (10.21±1.08 ) rmg/L, which were significantly higher than those in sham operation group (1723 ± 57 )U/L, (134.09 ± 31.36 )pg/ml and (4.33 ±0.49)mg/L, P ＜0.01]. The serum levels of amylase, TNF-α, D-lactic acid in PTX group were (7965 ± 318 ) U/L, (238.48 ± 44.35 ) pg/ml and ( 8.75 ± 1.28 ) mg/L, which were significantly lower than those in ANP group, but they were significantly higher than those in sham group ( P＜0.05 or ＜0.01). The positive rate of ZO-1 was (3.29±0.36)% in sham operation group, and it was (1.91 ± 0. 32)% in ANP group,which was significantly lower than that in sham operation group (P ＜ 0.05 ); and the value was (2.53±0.43)%in PTX group, which was lower than that in sham group, but it was higher than that in ANP group(P＜0.05).Conclusions PTX may attenuate intestinal barrier function injury by decreasing the breakdown of intestinal ZO-1.