首页|Protective effect of nitric oxide on hepatopulmonary syndrome from ischemia-reperfusion injury

Protective effect of nitric oxide on hepatopulmonary syndrome from ischemia-reperfusion injury

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AIM:To evaluate immunological protection of nitric oxide (NO) in hepatopulmonary syndrome and probable mechanisms of ischemia-reperfusion (IR) injury in rat liver transplantation.METHODS:Sixty-six healthy male Wistar rats were randomly divided into three groups (11 donor/recipient pairs).In group Ⅱ,organ preservation solution was lactated Ringer's solution with heparin 10 000/μL at 4 ℃.In groups Ⅰ and Ⅲ,the preservation solution added,respectively,L-arginine or NG-L-arginine methyl ester (L-NAME) (1 mmol/L) based on group Ⅱ,and recipients were injected with L-arginine or L-NAME (50 mg/kg) in the anhepatic phase.Grafted livers in each group were stored for 6 h and implanted into recipients.Five rats were used for observation of postoperative survival in each group.The other six rats in each group were used to obtain tissue samples,and executed at 3 h and 24 h after transplantation.The levels of alanine aminotransferase (ALT),tumor necrosis factor (TNF)-α and NO metabolites (NOx) were detected,and expression of NO synthase,TNF-α and intercellular adhesion molecule 1 (ICAM-1) was examined by triphosphopyridine nucleotide diaphorase histochemical and immunohistochemical staining.RESULTS:By supplementing L-arginine to strengthen the NO pathway,a high survival rate was achieved and hepatic function was improved.One-week survival rate of grafted liver recipients in group Ⅰ was significantly increased (28.8 ± 36.6 d vs 4 ± 1.7 d,P＜ 0.01) as compared with groups Ⅱ and Ⅲ.Serum levels of ALT in group Ⅰ were 2-7 times less than those in groups Ⅱ and Ⅲ (p ＜ 0.01).The cyclic guanosine monophosphate (cGMP) levels in liver tissue and NOx in group Ⅰ were 3-4 times higher than those of group Ⅱ after 3 h and 24 h reperfusion,while in group Ⅲ,they were significantly reduced as compared with those in group Ⅱ (P ＜ 0.01).The levels of TNF-α in group Ⅰ were significantly lower than in group Ⅱ after 3 h and 24 h reperfusion (P ＜ 0.01),while being significantly higher in group Ⅲ than group Ⅱ (P ＜ 0.01).Histopathology revealed more severe tissue damage in graft liver and lung tissues,and a more severe inflammatory response of the recipient after using NO synthase inhibitor,while the pathological damage to grafted liver and the recipient's lung tissues was signifcantly reduced in group Ⅰ after 3 h and 24 h reperfusion.A small amount of constitutive NO synthase (cNOS) was expressed in liver endothelial cells after 6 h cold storage,but there was no expression of inducible NO synthase (iNOS).Expression of cNOS was particularly significant in vascular endothelial cells and liver cells at 3 h and 24 h after reperfusion in group Ⅱ,but expression of iNOS and ICAM-1 was low in group Ⅰ.There was diffuse strong expression of ICAM-1 and TNF-α in group Ⅲ at 3 h after reperfusion.CONCLUSION:The NO/cGMP pathway may be critical in successful organ transplantation,especially in treating hepatopulmonary syndrome during cold IR injury in rat orthotopic liver transplantation.

Nitric oxideNitric oxide synthaseImmunoregulatoryHepatopulmonary syndromeIschemiareperfusion injuryOrthotopic liver transplantation

Tong-Jin Diao、Xin Chen、Li-Hua Deng、Han-Xiang Chen、Yan Liang、Xiao-Dong Zhao、Qing-Hua Wang

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Department of Hepatobiliary Surgery and Liver Transplant Center, Jinan Military Region, The Chinese PLA 401st Hospital, Qingdao 266071, Shandong Province, China

Department of Emergency, The People's Hospital of Chengyang District, Qingdao 266109, Shandong Province, China

Central Injection Room, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China

Institute of Pathogenic Biology, School of Medicine, Shandong University, Jinan 250012, Shandong Province, China

College of Marine Life Sciences, Ocean University of China, Qingdao 266003, Shandong Province, China

Department of General Surgery, Jinan Military Region, the Chinese PLA 401st Hospital, Qingdao 266071, Shandong Province, China

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2012

10.3748/wjg.v18.i25.3310

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(25)
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