高压氧下调低氧诱导因子对急性胰腺炎的影响

The effect of hyperbaric oxygen on acute pancreatitis through downregulating hypoxia-inducible factor

目的观察高压氧（HBO）抑制低氧诱导因子（HIF）活化对急性胰腺炎（AP）的影响。方法40只Wistar大鼠随机分为假手术组、AP组、吸氧组和HBO组，每组10只。造模后dh，吸氧组和14BO组大鼠分别接受常压下吸氧治疗和HBO治疗90min；造模后6h检测大鼠体内氧代谢水平；以免疫组织化学、激光共聚焦显微镜和Western blot法分析胰腺组织中HIF活化及血管内皮生长因子（VEGF）表达情况，检测胰腺组织髓过氧化物酶（MPO）含量和主要脏器干湿重比，以血清TNF—α和胰腺组织病理学评分评估病情。结果免疫组织化学证实，AP组、吸氧组和HBO组腺泡细胞及中性粒细胞内HIF活化进入细胞核，并伴有VEGF高表达；与AP组[PaO2：（86．6±5．6）mmHg（1mmHg=0．133kPa）；SaO2：87．7％±1．8％]和吸氧组[PaO2：（86．6±5．6）mmHg；SaO2：91．2％±2．5％]比较，HBO组[PaO2：（369．1±67．6）mmHg；SaO2：99．6％±0．7％]大鼠体内氧代谢水平升高（P〈0．05）；胰腺组织中HIF、VEGF和MPO含量减少，胰腺及胰外脏器水肿减轻，血清TNF—α和胰腺组织病理学评分降低（P〈0．05）。结论HIF可促进AP炎症反应，HBO可以通过抑制HIF活化改善AP病情。

Objective To observe the therapeutic effect of hyperbaric oxygen （HBO） on acute pancreatitis（AP） by downregulating hypoxia-inducible factor （HIF）. Methods Forty Wistar rats were randomly divided into 4 groups （n = 10 ）：sham group, AP group, normo-oxygen group （NP） and HBO group. At 4 hours after taurocholate-induced AP, the rats of NP group and HBO group were respectively treated with oxygen or HBO for 90 rain. Several parameters were measured to evaluate oxygen stress after treatment including oxygen saturation （SaO2 ）, partial pressure of oxygen （PO2 ）, pH, and serum LDH. Pancreatic tissues were subjected to histopathological analysis, immunostained, and homogenized for Western blotted analysis of HIF-1α and VEGF, and measuring myeloperoxidase activity. The serum TNF-α and pancreatic histopathological scores were evaluated the severity of AP. Results It was proved by immunohistochemisty that HIF in acinar cell and polymorphonuclear leukocytes （ PMNs ） was activated and transferred from cytoplasm into nucleus in AP group, NP group, and HBO group, following upregulation of VEGF. HBO therapy elevated blood SaO2 （99. 6% ± 0. 7% vs. 87.7% ± 1.8% or 91.2% ± 2. 5%, P 〈 0.05） and PaO2[ （369. 1 ±67.6）mm Hg（1 mm Hg =0. 133 kPa） vs. （86.6±5.6）mm Hg or （99.9 ± 4. 0） mm Hg, P 〈 0.05 ] . HBO therapy attenuated the severity of AP through inhibiting AP-indueed upregulation of HIF-1α and VEGF, as evidenced by reducing histopathological scores （ 12.40 ± 1.21 vs. 16.45 ± 1.10 or 16. 38 ± 1.10, P 〈 0. 05） , dry/wet weight ratio of pancreatic tissues, and myeloperoxidase activity. Conclusions HIF-1α plays a key role in the pathogenesis of AP. HBO therapy attenuates the severity of AP through downregulating the expression of HIF-1α.