奥曲肽对大鼠胰腺移植缺血再灌注损伤的保护机制  

Protective mechanism of Octreotide on ischemia-reperfusion injury following whole pancreaticoduodenal transplantation in rats

作　　者：程若川[1] 刁畅[1] 魏晓岗[1] 钱军[1] 罗华友[1] 冯曜宇[1] 

机构地区：[1]昆明医学院第一附属医院普通外科,650031

出　　处：《中华实验外科杂志》2004年第8期909-911,共3页Chinese Journal of Experimental Surgery

摘　　要：目的 探讨奥曲肽在胰腺移植缺血再灌注损伤中的作用以及可能机制。方法 应用大鼠全胰十二指肠同种异体移植动物模型,监测再灌注3、6 h血清中一氧化氮(NO)水平和超氧化物歧化酶(SOD)活性的变化,同时对移植胰进行组织学观察和诱导性一氧化氮合酶(iNOS)的免疫组织化学分析,以及应用奥曲肽和硝酸甘油(NTG)后上述指标的变化。结果 再灌注3、6 h血清NO水平、SOD活性分别为(77.13±5.29)、(103.92±11.17)μmol/L和(64.46±7.03)、(56.54±7.82)Nu/ml,与同时点假移植组差异有显著性(P均<0.01),且两指标变化呈显著负相关。应用奥曲肽后能显著降低NO水平,提高SOD活性接近至假移植组水平,与移植组相比差异有显著性(P均<0.01),并明显改善移植组织病变和降低iNOS表达强度。加用NTG后,又能在奥曲肽组基础上部分扭转上述变化,但这种现象仅在再灌注3 h时见到。结论 奥曲肽能显著下调移植胰iNOS的表达,降低血清NO水平并提高SOD活力,从而干扰NO/cGMP途径,减轻组织炎症反应,对再灌注组织起到保护作用。Objective To investigate the effects and possible mechanism of Octreotide during ischemia-reperfusion injury (I-RI) associated with pancreas transplantation in rats. Methods The homologous Sprague-Dawley rat model of heterotopic whole pancreaticoduodenal transplantation was used. The level of nitric oxide (NO) products (nitrite plus nitrate) and the activity of superoxide dismutase (SOD) in serum were determined after 3 h and 6 h of reperfusion. The changes of histology and the expression of inducible nitric oxide synthase (iNOS) in grafted pancreas were detected by H&E stain and immunohistochemistry, respectively. Meanwhile the influence of Octreotide and Octreotide plus nitroglycerin (NTG) on those indexes also were observed. Results The level of NO and activity of SOD at 3 h and 6 h after reperfusion was (77.13 ± 5.29), ( 103.92 ± 11.17) μmol/L and (64.46 ± 7.03), (56.54 ± 7.82) Numl, respectively, significantly different from those in the group of sham transplantation (all P < 0.01). Furthermore, there was a negative correlation in the changes between NO and SOD. The level of NO was remarkably decreased, the activity of SOD was increased to the level of the group of sham transplantation, the lesion was improved and the expression of iNOS in grafted tissue was inhibited after the administration of Octreotide. The changes could be partially reversed on the basis of the group of Octreotide when NTG was added to perfusate and preservation solution at 3 h after reperfusion. However, the phenomenon couldn't be seen at 6 h after reperfusion. Conclusion Octreotide could significantly inhibit the expression of iNOS and the level of NO, increase the activity of SOD at the same time. It has the protective effect on I-RI associated with pancreas transplantation in rats.

关 键 词：奥曲肽 胰腺移植 缺血再灌注损伤 NO水平 血清 大鼠 NOS NO/CGMP 组织病变 超氧化物歧化酶(SOD) 

分 类 号：R96[医药卫生—药理学]