蛋白酶体抑制剂MG132减轻大鼠移植胰腺缺血再灌注损伤的作用  

Protective effect of MG132 on ischemia-reperfusion injury after pancreaticoduodenal transplantation in rats

作　　者：张力[1] 赵雪云[1] 刘胜春[1] 

机构地区：[1]重庆医科大学附属第一医院内分泌乳腺外科,400016

出　　处：《中华器官移植杂志》2013年第6期358-361,共4页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金（30871295,81272265）;重庆市科委科技攻关项目（2012gg-yyis10041）

摘　　要：目的研究蛋白酶体抑制剂MG132减轻大鼠移植胰腺缺血再灌注（IR）损伤的作用及其机制。方法采用随机数字表法将SD大鼠分为假手术组、IR组和MG132组，IR组和MG132组建立同系大鼠胰腺十二指肠移植模型。分别于再灌注后1、3、6h，检测受鼠血清淀粉酶含量，光镜下观察胰腺组织病理变化，采用蛋白质印迹法测定胰腺组织中核因子-κB（NF-κB）P65蛋白的水平，采用免疫组织化学和逆转录聚合酶链反应法分别检测胰腺组织中肿瘤坏死因子α（TNF-α）和细胞间黏附因子-1（ICAM-1）的表达情况。结果与假手术组比较，IR组再灌注后相同时点的组织病理损伤明显较重，血清淀粉酶含量、胰腺组织中P65蛋白水平以及TNF-α和ICAM-I水平均明显上升；与IR组比较，MG132组相同时点的组织损伤减轻，血清淀粉酶含量、胰腺组织中P65蛋白水平及TNFa和ICAM-1水平均明显降低。结论MG132能够减轻大鼠移植胰腺的IR损伤，其机制可能是通过抑制NF-κB的活化，从而下调TN-α和ICAM-1的表达。Objective To investigate the protective effects of Proteasome inhibitor MG132 on ischemi-reperfusion injury （IRI） after pancreas transplantation in rats, and the possible mechanism. Method Fifteen normal SD rats were allocated into the sham operation group. In the allogenie male SD rats, the model of pancreas transplantation was established. The recipients were divided into another two groups （n = 15 each） at random： IRI group and the MG132 pretreatment group. Serum amylase level was determined at 1, 3 and 6 h after the operation. Pancreas samples were harvested at the same time for pathological study by light microscopy. The expression of NF-κB P65 protein in the pancreas was detected by using Western blotting. The expression of TNF-α and ICAM-1 in the pancreas was detected by using immunohistochemistry and RT-PCR. Result Tissue damage on IRI group was more severe than in sham operation group. The level of serum amylase, and the expression of P65, TNF-α and ICAM-1 were higher in IRI group than those in sham operation group （P〈0. 05）. Tissue damage in MG132 pretreatment group was milder than in IR1 group. The level of serum amylase, and the expression of P65, TNF-α and ICAM-1 were lower in MG132 pretreatment group than in IRI group （P〈0. 05）. Conclusion MG132 pretreatment can alleviate the pancreas IRI after pancreas transplantation, probably by inhibiting the activation of NF-κB, and the inhibition effect can down-regulate the expression of TNF-α and ICAM-1.

关 键 词：大鼠 胰腺移植 再灌注损伤 蛋白酶体抑制剂 核因子ΚB 

分 类 号：R285.5[医药卫生—中药学]