大鼠重症急性胰腺炎内毒素血症、细胞因子和一氧化氮的变化及善宁的治疗作用

Changes of endotoximia, cytokines and nitric oxide and therapeutic effects of sandostatin in rats with severe acute pancreatitis

目的:探讨内毒素血症、细胞因子和一氧化氮在重症急性胰腺炎(severe acuce pancreatitis, SAP)发展中的作用及善宁的治疗作用．方法:经胰管逆行注射15 g/L去氧胆酸钠建立SAP模型,给予善宁治疗,观察造模后各时间点血中内毒素(ET)、过氧化脂质(LPO), TNF-α,IL-6,一氧化氮(NO)的变化,并进行相关分析;于24 h后取胰腺组织,测定胰腺组织中LPO,TNF-α,IL-6和NO水平,同时进行相关分析及胰腺组织病理学检查．结果:与对照组比较,SAP组各时间点血浆 ET,LPO,TNF-α,IL-6,NO的水平明显升高 (P<0．01),其中ET,LPO,TNF-α和NO 6 h尤为显著(898±114 EU/L,24．58±1．23 μmol/L, 246．3±16．5 ng／L,162．8±10．9 mmol／L,P< 0．05 vs 12,24 h)．胰腺组织LPO,TNF-α,IL-6, NO的水平SAP组明显高于对照组(3．31±0．85 μmol/g vs 0．33±0．04 μmol/g,P<0．01:2．57± 0．14 ng/g vs 0．16±0．04 ng/g,P<0．01;85．6± 24．6 ng/g vs 32．5±5．7 ng/g,P<0．01;15．3± 1．2 mmol／g vs 6．6±1．4 mmol/g,P<0．01),光镜下胰腺组织病理损害明显．相关分析显示 SAP组血浆LPO,TNF-α,IL-6,NO水平分别与ET水平呈显著正相关(r=0．858,P<0．01:r =0．958,P<0．01;r=0．918,P<0．01;r=0．875, P<0．01)．善宁治疗后上述各指标均较SAP组明显改善(P<0．01)．结论:ET血症、细胞因子、NO等相互激发、相互促进,在SAP的发展中起着重要的协同作用．善宁能阻断这些损伤因子的连锁反应．

AIM： To study the roles of endotoximia, cytokines and nitric oxide in the development of severe acute pancreatitis （SAP） and the therapeutic effects of sandostatin （SS） in rats. METHODS： SAP models were induced by retrograde injection of 15 g/L sodium deoxycholate and then treated by SS. The plasma levels of endotoxin （ET）, lipid peroxide （LPO）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and nitric oxide （NO）, as well as the expression LPO, TNF-α, IL-6 and NO in pancreatic tissues, were measured. The changes of pancreatic histology were examined under light microscope. RESULTS： As Compared with those in sham operation group, the plasma levels of ET, LPO, TNF-α, IL-6 and NO were markedly higher in SAP group （P 〈 0.01）, and the changes of ET, LPO, TNF-α and NO at 6 h were higher （898 ± 114 EU/L, 24.58 ± 1.23 μmol/L, 246.3 ± 16.5 ng/L, 162.8 ± 10.9 mmol/L, P 〈 0.05） than those at 12 and 24 h. The changes of LPO, TNF-α, IL-6 and NO in pancreatic tissues of SAP group were obviously higher in comparison with those of sham group （3.31 ± 0.85 μmol/g vs 0.33 ± 0.04 μmol/g, P 〈 0.01; 2.57 ± 0.14 ng/g vs 0.16 ± 0.04 ng/g, P 〈 0.01; 85.6 ± 24.6 ng/g vs 32.5 ± 5.7 ng/g, P 〈 0.01; 15.3 ± 1.2 mmol/g vs 6.6 ± 1.4 mmol/g, P 〈 0.01）; and severe damages of pancreatic tissues were observed under light microscope. In SAP group, the plasma levels of LPO, TNF-α, IL-6 and NO were significantly correlated with ET level （r = 0.858, P 〈 0.01; r = 0.958, P 〈 0.01; r = 0.918, P 〈 0.01; r = 0.875, P 〈 0.01）. The indexes mentioned above in SS group were obviously ameliorated in comparison with those in SAP group （P 〈 0.01）. CONCLUSION： Endotoximia, cytokines and NO play important roles in the development of severe acute pancreatitis. Sandostatin can block the chain reaction caused by these factors.