钴原卟啉对大鼠急性胰腺炎的抑制作用及其机制  

Pretreatment with cobalt protoporphyrin protects against acute pancreatitis in rats

作　　者：郑立君[1] 彭上晋[2] 房林[1] 李晴[1] 丁卫星[1] 

机构地区：[1]同济大学附属第十人民医院普外科,上海市200072 [2]复旦大学附属金山医院普外科,上海市200540

出　　处：《世界华人消化杂志》2010年第34期3685-3689,共5页World Chinese Journal of Digestology

基　　金：上海市卫生局科研课题基金资助项目No.2007Y32~~

摘　　要：目的:探讨钴原卟啉(cobalt protoporphyrin,CoPP)对急性胰腺炎的抑制作用及其机制.方法:将90只SD大鼠随机分为假手术组(SO组)、胰腺炎组(AP组)和应用CoPP组(CoPP组).各组大鼠手术后6、12、24h处死,光镜下观察胰腺病理改变,测定血清淀粉酶水平,ELISA方法测定血清肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6),实时定量PCR检测外周血单核细胞(PBMC)和胰腺组织中血红素氧合酶-1(HO-1)mRNA的表达.结果:与SO组相比,AP组和CoPP组在各时间点上胰腺组织水肿、炎性细胞浸润并伴有出血坏死等改变,胰腺组织病理评分均明显上升(24h:9.13±1.02,9.42±0.87vs0.00±0.00,均P<0.01);血清淀粉酶、TNF-α、IL-6水平均明显升高(24h:8991.7U/L±911.54U/L,8298.0U/L±1015.67U/L vs819.1U/L±177.81U/L;157.84ng/L±19.72ng/L,142.09ng/L±22.6ng/L vs25.71ng/L±0.84ng/L;552.92ng/L±72.96ng/L,511.03ng/L±57.76ng/L vs89.51ng/L±14.73ng/L,均P<0.01).经CoPP诱导后显著促进了PBMC及胰腺组织的HO-1mRNA表达(24h:2.795±0.282,5.174±0.631vs0.780±0.105;16.436±2.219,28.902±3.791vs5.604±0.988,均P<0.05).CoPP组早期(术后6、12h)的胰腺组织病理评分、血清淀粉酶、TNF-α、IL-6水平较AP组明显下降(t=5.08,3.74;t=4.38,5.32;t=6.19,5.03;t=4.92,3.65,均P<0.01).结论:急性胰腺炎早、中期应用HO-1诱导剂CoPP可抑制炎症反应发挥减轻胰腺损伤的作用,这与其上调HO-1mRNA的表达,从而抑制细胞因子的产生密切相关.AIM：To investigate the protective effect of cobalt protoporphyrin（CoPP）against acute pancreatitis（AP）in rats and to explore possible mechanisms involved.METHODS：Ninety Sprague-Dawley rats were randomly divided into three groups（n=30 for each group）：sham operation（SO）group,AP group,CoPP group.At 6,12,and 24 h after AP induction,pancreatic pathological changes and serum levels of amylase,tumor necrosis factor-α（TNF-α）,and interleukin-6（IL-6）were detected and compared among different groups.The expression of heme oxygenase-1（HO-1）mRNA in peripheral blood mononuclear cells（PMBCs）and pancreatic tissue were measured by real-time quantitative reverse transcription-polymerase chain reaction（RT-PCR）.RESULTS：At 6,12,and 24 h after the surgi-cal procedure,rats of the AP and CoPP groups showed typical histopathological changes of AP.The pathological score of pancreatic tissue（24 h：9.13±1.02,9.42±0.87 vs 0.00±0.00,both P0.01）and serum levels of serum amylase,TNF-α,and IL-6（24 h：8 991.7 U/L±911.54 U/L,8 298.0 U/L±1 015.67 U/L vs 819.1 U/L ±177.81 U/L;157.84 ng/L±19.72 ng/L,142.09 ng/L±22.6 ng/L vs 25.71 ng/L±0.84 ng/L;552.92 ng/L±72.96 ng/L,511.03 ng/L±57.76 ng/L vs 89.51 ng/L±14.73 ng/L,all P0.01）in the AP and CoPP groups were significantly elevated compared with the SO group.Pretreat-ment with CoPP up-regulated the expression of HO-1 mRNA in PBMCs and pancreatic tissue（24 h：2.795±0.282,5.174±0.631 vs 0.780±0.105;16.436±2.219,28.902±3.791 vs 5.604±0.988,all P0.05）.Compared with the AP group,at 6 and 12 h after AP induction,the CoPP group had significantly alleviated pathological alterations,and lower pathological score,serum levels of amylase,TNF-αand IL-6（t=5.08,3.74;t=4.38,5.32;t=6.19,5.03;t=4.92,3.65,all P0.01）.CONCLUSION：Pretreatment with CoPP can modulate inflammatory reaction and decrease pancreatic injury in AP rats via mechanisms that may be closely related to up-regulation of HO-1 expression to inhibit cytokine production.

关 键 词：钴原卟啉 急性胰腺炎 血红素氧合酶-1 实时定量PCR 

分 类 号：R576[医药卫生—消化系统]