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垂体腺苷酸环化酶激活肽-38对肠缺血再灌注及自体移植的影响与变化

Changes and effect of PACAP-38 on intestinal ischemia-reperfusion and autotransplantation.

作者信息

Ferencz A, Rácz B, Tamás A, Nedvig K, Németh J, Kalmár-Nagy K, Horváth O P, Wéber Gy, Röth E, Reglödi D

机构信息

Department of Surgical Research and Techniques, University of Pécs, Pécs, Hungary.

出版信息

Transplant Proc. 2009 Jan-Feb;41(1):57-9. doi: 10.1016/j.transproceed.2008.10.084.

Abstract

Tissue injury caused by cold preservation and reperfusion during small bowel transplantation remains an unsolved problem. Increasing evidence suggests that pituitary adenylate cyclase-activating polypeptide (PACAP) has protective effects in several ischemia-reperfusion (I/R) models. This study investigated the effect of PACAP-38 on oxidative stress in autotransplanted intestine. We established sham-operated, I/R, and autotransplanted groups in Wistar rats (n = 55). We applied ischemia for 1 (GI), 2 (GII), or 3 hours (GIII). In autotransplanted groups, we performed total orthotopic intestinal autotransplantation. Grafts were preserved in University of Wisconsin (UW) solution for 1 (GIV), 2 (GV), 3 (GVI), or 6 (GVII) hours and in PACAP-38-containing UW for 1 (GVIII), 2 (GIX), 3 (GX), or 6 (GXI) hours. Reperfusion lasted 3 hours in each group. Endogenous PACAP-38 values were measured by radioimmunoassay. Oxidative stress parameters malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured in tissue homogenates. Concentration of endogenous PACAP-38 significantly decreased in GI to GIII compared with the sham-operated animals following I/R periods (P < .05). Cold preservation in UW and reperfusion of the intestine increased the level of tissue MDA in GIV to GVII, which correlated with the duration of cold storage. The content of GSH decreased in GIV to GVII to levels that were significantly different between GIV and GVIII and between GVII and GXI. SOD activity decreased dramatically in GIV to GVII with significantly higher activity in GIX to GXI. Our findings confirmed that I/R decreased endogenous PACAP-38 concentration. Administration of PACAP-38 to UW solution mitigated the oxidative injury during intestinal autotransplantation.

摘要

小肠移植过程中冷保存和再灌注引起的组织损伤仍是一个未解决的问题。越来越多的证据表明,垂体腺苷酸环化酶激活多肽(PACAP)在几种缺血再灌注(I/R)模型中具有保护作用。本研究探讨了PACAP-38对自体移植肠氧化应激的影响。我们在Wistar大鼠中建立了假手术组、I/R组和自体移植组(n = 55)。我们进行了1小时(GI组)、2小时(GII组)或3小时(GIII组)的缺血处理。在自体移植组中,我们进行了全原位肠道自体移植。移植物在威斯康星大学(UW)溶液中保存1小时(GIV组)、2小时(GV组)、3小时(GVI组)或6小时(GVII组),并在含PACAP-38的UW溶液中保存1小时(GVIII组)、2小时(GIX组)、3小时(GX组)或6小时(GXI组)。每组再灌注持续3小时。通过放射免疫分析法测定内源性PACAP-38值。在组织匀浆中测量氧化应激参数丙二醛(MDA)、还原型谷胱甘肽(GSH)和超氧化物歧化酶(SOD)。与假手术动物相比,I/R期后GI至GIII组内源性PACAP-38浓度显著降低(P < 0.05)。UW溶液中的冷保存和肠道再灌注使GIV至GVII组的组织MDA水平升高,这与冷保存时间相关。GIV至GVII组中GSH含量降低,GIV组与GVIII组以及GVII组与GXI组之间的水平存在显著差异。GIV至GVII组中SOD活性显著降低,GIX至GXI组活性显著更高。我们的研究结果证实,I/R降低了内源性PACAP-38浓度。将PACAP-输入UW溶液可减轻肠道自体移植过程中的氧化损伤。

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