Effect of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase mRNA Expressions on Lung Injury of Rats with Acute Necrotizing Pancreatitis　_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Lei , WANG Weixing , YU Jia , DENG Wenhong , CHEN Chen , CHEN Xiaoyan , CUI Zhoujun.

Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China;

Corresponding author：

Keywords：

Acute pancreatitis; Lung injury; Inducible nitric oxide synthase; Endothelial nitric oxide synthase; Gene expression

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Objective Observing the expressions of inducible nitric oxide synthase （iNOS） and endothelial nitric oxide synthase （eNOS） mRNA in lung tissues of rats with acute necrotizing pancreatitis （ANP） to explore the role of NOS in ANP associated-lung injury.
Methods Forty Wistar rats were assigned into ANP group (n=30) and sham-operation group (SO group, n=10). ANP model was induced by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct. Pathological changes of the lung tissue were observed under light microscope at 3 h, 6 h and 12 h after the ANP-model operation, and the expressions of iNOS mRNA and eNOS mRNA in lung tissue were assayed by RT-PCR. Results Different degrees of pathological changes of the lung tissue, such as hyperemia, edema, inflammatory cells infiltration, hemorrhage and necrosis, were found in the ANP group. The pathologic injury scores of lung tissue in ANP group were higher than that in SO group (P lt;0.05), and gradually increased with the duration extension of ANP (P lt;0.05). Compared with the SO group, the expressions of iNOS and eNOS mRNA in ANP group were all higher at 3 h, 6 h, and 12 h (P lt;0.05).
Conclusions The overexpressions of iNOS and eNOS mRNA may play important roles in lung injury of ANP. This provides us a theory basis that lung injury of ANP could be relieved by inhibiting the expressions of iNOS and eNOS mRNA.

Citation： LIU Lei,WANG Weixing,YU Jia,DENG Wenhong,CHEN Chen,CHEN Xiaoyan,CUI Zhoujun.. Effect of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase mRNA Expressions on Lung Injury of Rats with Acute Necrotizing Pancreatitis　. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(5): 449-453. doi: Copy

1.	Lund H, Tnnesen H, Tnnesen MH, et al. Long-term recurrence and death rates after acute pancreatitis [J]. Scand J Gastroenterol, 2006; 41(2): 234-238.
2.	Ozturk M, Mas MR, Yasar M, et al. The role of inducible nitric oxide synthase inhibitor, meropenem, and taurine in experimental acute necrotizing pancreatitis [J]. Pancreas, 2003; 26(4): 357-362.
3.	von Dobschuetz E, Schmidt R, Scholtes M, et al. Protective role of heme oxygenase-1 in pancreatic microcirculatory dysfunction after ischemia/reperfusion in rats [J]. Pancreas, 2008; 36(4): 377-384.
4.	张莹, 石承先, 别平, 等. 重症急性胰腺炎大鼠肺脏iNOS mRNA表达及丹参的干预效应 [J]. 第三军医大学学报, 2005; 27(15): 1569-1572.
5.	Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease [J]. Physiol Rev, 2007; 87(1): 315-424.
6.	Schmidt J, Lewandrowsi K, Warshaw AL, et al. Morphometric characteristics and homogeneity of a new model of acute pancreatitis in the rat [J]. Int J Pancreatol, 1992; 12(1): 41-51.
7.	Osman MO, Kristensen JU, Jacobsen NO, et al. A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits [J]. Gut, 1998; 43(2): 232-239.
8.	Moncada S, Higgs A. The L-arginine-nitric oxide pathway [J]. N Engl J Med, 1993; 329(27): 2002-2012.
9.	Vassalli G, Dichek DA. Gene therapy for arterial thrombosis [J]. Cardiovasc Res, 1997; 35(3): 459-469.
10.	Werner J, Fernández-del Castillo C, Rivera JA, et al. On the protective mechanisms of nitric oxide in acute pancreatitis [J]. Gut, 1998; 43(3): 401-407.
11.	Molero X, Guarner F, Salas A, et al. Nitric oxide modulates pancreatic basal secretion and response to cerulein in the rat: effects in acute pancreatitis [J]. Gastroenterology, 1995; 108(6): 1855-1862.
12.	Hauser B, Matejovic M, Radermacher P. Nitric oxide, leukocytes and microvascular permeability: causality or bystanders? [J]. Crit Care, 2008; 12(1): 104.
13.	刘会芳, 赵燕燕, 崔玉英, 等. 川芎嗪对急性百草枯中毒大鼠一氧化氮和诱导型一氧化氮合酶的影响及其治疗作用 [J]. 时珍国医国药, 2009; 20(7): 1631-1632.
14.	Liaudet L, Soriano FG, Szabó C. Biology of nitric oxide signaling [J]. Crit Care Med, 2000; 28(4 Suppl): N37-N52.
15.	Thomas DD, Ridnour LA, Isenberg JS, et al. The chemical biology of nitric oxide: implications in cellular signaling [J]. Free Radic Biol Med, 2008; 45(1): 18-31.
16.	Mohr S, Hallak H, de Boitte A, et al. Nitric oxide-induced S-glutathionylation and inactivation of glyceraldehyde-3-phosphate dehydrogenase [J]. J Biol Chem, 1999; 274(14): 9427-9430.
17.	孙雄, 龚镭, 谈春晓, 等. 急性胆源性胰腺炎患者血清NO、SOD、CAT 的变化及其临床意义 [J]. 南京医科大学学报(自然科学版), 2008; 28(10): 1290-1292.
18.	Camargo EA, Delbin MA, Ferreira T, et al. Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries [J]. BMC Gastroenterol, 2008; 8: 19.
19.	张玉清, 乔建国, 谭最. 选择性iNOS 抑制剂治疗重症急性胰腺炎的实验研究 [J]. 陕西医学杂志, 2003; 32(5): 473-475.
20.	Kutzsche S, Lyberg T, Bjertnaes LJ. et al. Effects of adenosine on extravascular lung water content in endotoxemic pigs [J]. Crit Care Med, 2001; 29(12): 2371-3276.
21.	Ang AD, Adhikari S, Ng SW, et al. Expression of nitric oxide synthase isoforms and nitric oxide production in acute pancreatitis and associated lung injury [J]. Pancreatology, 2009; 9(1-2): 150-159.
22.	Adhikari NK, Burns KE, Friedrich JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis [J]. BMJ, 2007; 334(7597): 779.
23.	张剑, 何生, 李茂德. 肝细胞癌中iNOS和p53蛋白的表达及其与肿瘤血管形成的关系 [J]. 中国普外基础与临床杂志, 2004; 11(5): 396-398.
24.	Ayub K, Serracino-Inglott F, Williamson RC, et al. Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion [J]. Br J Surg, 2001; 88(9): 1189-1193.
25.	Wink DA, Mitchell JB. Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide [J]. Free Radic Biol Med, 1998; 25(4-5): 434-456.
26.	宋文哲, 宋燕, 谭岩, 等. 氨基胍对内毒素休克大鼠肝损伤的保护作用研究 [J]. 中国普外基础与临床杂志, 2003; 10(4): 347-350.
27.	Szabó C. Multiple pathways of peroxynitrite cytotoxicity [J]. Toxicol Lett, 2003; 140-141: 105-112.

1. Lund H, Tnnesen H, Tnnesen MH, et al. Long-term recurrence and death rates after acute pancreatitis [J]. Scand J Gastroenterol, 2006; 41(2): 234-238.
2. Ozturk M, Mas MR, Yasar M, et al. The role of inducible nitric oxide synthase inhibitor, meropenem, and taurine in experimental acute necrotizing pancreatitis [J]. Pancreas, 2003; 26(4): 357-362.
3. von Dobschuetz E, Schmidt R, Scholtes M, et al. Protective role of heme oxygenase-1 in pancreatic microcirculatory dysfunction after ischemia/reperfusion in rats [J]. Pancreas, 2008; 36(4): 377-384.
4. 张莹, 石承先, 别平, 等. 重症急性胰腺炎大鼠肺脏iNOS mRNA表达及丹参的干预效应 [J]. 第三军医大学学报, 2005; 27(15): 1569-1572.
5. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease [J]. Physiol Rev, 2007; 87(1): 315-424.
6. Schmidt J, Lewandrowsi K, Warshaw AL, et al. Morphometric characteristics and homogeneity of a new model of acute pancreatitis in the rat [J]. Int J Pancreatol, 1992; 12(1): 41-51.
7. Osman MO, Kristensen JU, Jacobsen NO, et al. A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits [J]. Gut, 1998; 43(2): 232-239.
8. Moncada S, Higgs A. The L-arginine-nitric oxide pathway [J]. N Engl J Med, 1993; 329(27): 2002-2012.
9. Vassalli G, Dichek DA. Gene therapy for arterial thrombosis [J]. Cardiovasc Res, 1997; 35(3): 459-469.
10. Werner J, Fernández-del Castillo C, Rivera JA, et al. On the protective mechanisms of nitric oxide in acute pancreatitis [J]. Gut, 1998; 43(3): 401-407.
11. Molero X, Guarner F, Salas A, et al. Nitric oxide modulates pancreatic basal secretion and response to cerulein in the rat: effects in acute pancreatitis [J]. Gastroenterology, 1995; 108(6): 1855-1862.
12. Hauser B, Matejovic M, Radermacher P. Nitric oxide, leukocytes and microvascular permeability: causality or bystanders? [J]. Crit Care, 2008; 12(1): 104.
13. 刘会芳, 赵燕燕, 崔玉英, 等. 川芎嗪对急性百草枯中毒大鼠一氧化氮和诱导型一氧化氮合酶的影响及其治疗作用 [J]. 时珍国医国药, 2009; 20(7): 1631-1632.
14. Liaudet L, Soriano FG, Szabó C. Biology of nitric oxide signaling [J]. Crit Care Med, 2000; 28(4 Suppl): N37-N52.
15. Thomas DD, Ridnour LA, Isenberg JS, et al. The chemical biology of nitric oxide: implications in cellular signaling [J]. Free Radic Biol Med, 2008; 45(1): 18-31.
16. Mohr S, Hallak H, de Boitte A, et al. Nitric oxide-induced S-glutathionylation and inactivation of glyceraldehyde-3-phosphate dehydrogenase [J]. J Biol Chem, 1999; 274(14): 9427-9430.
17. 孙雄, 龚镭, 谈春晓, 等. 急性胆源性胰腺炎患者血清NO、SOD、CAT 的变化及其临床意义 [J]. 南京医科大学学报(自然科学版), 2008; 28(10): 1290-1292.
18. Camargo EA, Delbin MA, Ferreira T, et al. Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries [J]. BMC Gastroenterol, 2008; 8: 19.
19. 张玉清, 乔建国, 谭最. 选择性iNOS 抑制剂治疗重症急性胰腺炎的实验研究 [J]. 陕西医学杂志, 2003; 32(5): 473-475.
20. Kutzsche S, Lyberg T, Bjertnaes LJ. et al. Effects of adenosine on extravascular lung water content in endotoxemic pigs [J]. Crit Care Med, 2001; 29(12): 2371-3276.
21. Ang AD, Adhikari S, Ng SW, et al. Expression of nitric oxide synthase isoforms and nitric oxide production in acute pancreatitis and associated lung injury [J]. Pancreatology, 2009; 9(1-2): 150-159.
22. Adhikari NK, Burns KE, Friedrich JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis [J]. BMJ, 2007; 334(7597): 779.
23. 张剑, 何生, 李茂德. 肝细胞癌中iNOS和p53蛋白的表达及其与肿瘤血管形成的关系 [J]. 中国普外基础与临床杂志, 2004; 11(5): 396-398.
24. Ayub K, Serracino-Inglott F, Williamson RC, et al. Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion [J]. Br J Surg, 2001; 88(9): 1189-1193.
25. Wink DA, Mitchell JB. Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide [J]. Free Radic Biol Med, 1998; 25(4-5): 434-456.
26. 宋文哲, 宋燕, 谭岩, 等. 氨基胍对内毒素休克大鼠肝损伤的保护作用研究 [J]. 中国普外基础与临床杂志, 2003; 10(4): 347-350.
27. Szabó C. Multiple pathways of peroxynitrite cytotoxicity [J]. Toxicol Lett, 2003; 140-141: 105-112.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase mRNA Expressions on Lung Injury of Rats with Acute Necrotizing Pancreatitis　

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase mRNA Expressions on Lung Injury of Rats with Acute Necrotizing Pancreatitis 

Abstract Full text Figures/Tables Video References Cited by

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Effect of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase mRNA Expressions on Lung Injury of Rats with Acute Necrotizing Pancreatitis　