氨基胍对梗阻性黄疸大鼠治疗作用的实验研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对梗阻性黄疸大鼠的治疗作用及作用机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、假手术组、黄疸组、氨基胍治疗组4组,每组10只.通过测定治疗前后肝功、血胆红素、内毒素、乳酸、肝组织丙二醛水平,以及通过对肝脏、小肠的形态学分析来探讨氨基胍对梗阻性黄疽大鼠的治疗作用.结果 血浆内毒素和血清乳酸、肝组织丙二醛随着胆道梗阻时间的延长逐步升高,并伴随着肝脏小肠病理形态学的改变.氨基胍治疗组各项指标显著低于对照组,并能改善肝组织及小肠病理形态.结论 氨基胍(AG)可通过减轻脂质过氧化与内毒素血症发挥保护肝脏及小肠的作用,为治疗梗阻性黄疸患者提供了一种新的思路和方法.     

内毒素休克大鼠核因子κB活化规律及其在生物蝶呤诱生中的作用

目的观察内毒素休克大鼠血浆及主要脏器核因子(NF)κB活化规律及其对生物蝶呤(BH4)和一氧化氮(NO)表达水平的影响,探讨内毒素休克时NF-κB信号通路对BH4诱生NO的分子调控机制及其与多器官功能损害的关系。方法将47只大鼠按表格随机法分为正常组(8只)、内毒素／脂多糖(LPS)组(24只,每观察时相点8只,均同时注射LPS制成休克模型)和拮抗组[15只,每观察时相点5只,均同时注射LPS并以吡咯烷二硫代氨基甲酸盐(PDTC)拮抗]。休克及拮抗组于注射LPS后2、6、12 h观察,并与正常组同法处死,无菌留取大鼠血标本及肝、肺、肾组织,测定组织中NF-κB活性和三磷酸鸟苷环水解酶Ⅰ(GTP-CHⅠ)和诱导型一氧化氮合酶(iNOS)mRNA表达水平、血浆和组织中的BH4含量及NO水平、肝脏和肾脏功能指标、肺组织髓过氧化物酶活性。结果与正常组(例如肺组织中NF-κB活性为26±6)比较,LPS组大鼠组织中NF-κB迅速活化(P<0．01),并于注射后2 h达峰值(肺组织中为291±44);LPS组各组织中GTP-CHⅠ和iNOS mRNA表达、BH4和NO水平也较正常组明显升高(P<0．05或0．01),至伤后12 h仍持续较高水平。此外,该组相应器官功能均受到不同程度的损害。应用PDTC的拮抗组大鼠各组织中NF-κB活性均较LPS组有所降低,GTP-CHⅠ、iNOS mRNA表达及BH4、NO水平显著受抑,肝、肺、肾功能明显改善。结论内毒素休克时机体内NF-κB通路高度活化,并对BH4／NO系统具有明显调节效应;可通过下调BH4介导的iNOS的过度活化抑制NF-κB信号途径,从而减轻组织炎性反应,对机体脏器功能起到保护作用。     

一氧化氮、内皮素-1在内毒质所致肝脏损伤中的作用机制研究

目的 探讨一氧化氮（NO）和内皮素-1（ET-1）在内毒素所致肝脏损伤中的作用机制。方法 Waster大鼠40只随机分成对照组，内毒素组、内毒素组、内皮素受体拮抗剂组和左旋精氨酸组，观察各组大鼠血浆NO和ET-1水平，肝脏功能变化，在光镜下观察肝细胞损伤程度，在电镜下观察肝脏超微结构改变。结果 大鼠投予内毒素12h后，血浆NO和ET-1水平明显下升，血浆转氨酶水平增加，肝细胞明显水肿，变性和坏死，肝筛的数量和直径明显减少，左旋精氨酸和内皮素受体损坏抗剂均能明显减轻肝脏功能和结构的损伤，结论 在内毒素所致肝损伤中，NO起保护性作用，而ET-1则起促进作用，二者在肝脏中的作用可能是通过作用于肝筛而引起的。     

诱导型一氧化氮合酶及一氧化氮在肝动脉结扎大鼠肝损伤中的意义及高压氧治疗作用

目的探讨大鼠肝脏及血清诱导型一氧化氮合酶、一氧化氮在肝动脉结扎损伤中的意义及高压氧的治疗作用。方法雄性SD大鼠96只,随机分成3组:对照组(手术对照,肝动脉未结扎)、肝动脉结扎组(结扎组)和肝动脉结扎 高压氧治疗组(高压氧组)。每组分为术后1 d、3 d、7 d、14 d时间点。高压治疗于术后2 h开始,吸纯氧60 m in,2/日,检测肝脏和血清中iNOS及NO水平,血清丙氨酸氨基转移酶(ALT),肝脏常规病理检查。结果结扎组肝组织iNOS、NO水平7 d达峰值,结扎组7、14 d与高压氧组及对照组相比均明显增高(P<0.01)。血清iNOS水平7 d、14 d结扎组明显高于高压氧及对照组,结扎组3 d血清NO水平达峰值,3 d、7 d、14 d均较高压氧组明显升高(P<0.05)。高压氧治疗各组血清ALT均较结扎组明显降低,病理示结扎组肝细胞浊肿明显,有坏死灶形成,高压氧治疗组肝细胞未见坏死。结论iNOS及NO参与了肝动脉结扎肝损害过程,高压氧治疗改善肝损害作用机制可能为抑制iNOS及NO。     

细胞外信号调节激酶在内毒素休克大鼠生物喋呤诱生中的作用机制探讨

目的观察细胞外信号调节激酶（ERK）通路抑制剂对生物喋呤（BH4）和一氧化氮（NO）表达及核因子-kB（NF-kB）活化的影响,探讨内毒素休克时ERK信号通路与NF-kB的交汇作用及其对BH4诱生NO的调控机制。方法采用内毒素休克模型,60只大鼠随机分为正常对照组（n=8）、内毒素休克组（n=32）和ERK抑制剂PD98059拮抗组（n=20）。留取动物肝、肺、肾组织进行NF-kB活性分析以及三磷酸鸟苷环水解酶I（GTP—CHⅠ）、诱生型一氧化氮合酶（iNOS）基因表达的检测,并测定组织及血浆中BH4、NO水平。结果内毒素攻击可导致动物肝、肺、肾组织GTP-CHⅠ基因表达和BH4水平明显升高,至伤后24h仍持续于较高水平;与之相应,组织iNOS基因表达和NO水平亦明显升高;各组织NF-kB迅速活化,并于2h达峰值。采用PD98059处理后,内毒素休克动物肾组织GTP—CHⅠ mRNA表达明显受抑,肝、肺组织GTP—CHⅠmRNA表达仅呈现降低趋势;血浆及肝、肾组织中BH4水平12h显著降低;同样,各组织iNOS mRNA表达及NO水平早期亦显著降低。此外,PD98059处理组动物肝组织2～6h、肺组织2h、24h和肾组织24h时相点NF-KB活性显著降低。结论内毒素休克时抑制ERK通路,能部分下调BH4和NO表达与NF-kB的活化,表明ERK与NF-kB通路间可能存在交汇作用,共同参与了BH4诱生NO的调控作用。     

氨基胍对梗阻性黄疸大鼠治疗作用的实验研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对梗阻性黄疸大鼠的治疗作用及作用机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、假手术组、黄疸组、氨基胍治疗组4组,每组10只.通过测定治疗前后肝功、血胆红素、内毒素、乳酸、肝组织丙二醛水平,以及通过对肝脏、小肠的形态学分析来探讨氨基胍对梗阻性黄疽大鼠的治疗作用.结果 血浆内毒素和血清乳酸、肝组织丙二醛随着胆道梗阻时间的延长逐步升高,并伴随着肝脏小肠病理形态学的改变.氨基胍治疗组各项指标显著低于对照组,并能改善肝组织及小肠病理形态.结论 氨基胍(AG)可通过减轻脂质过氧化与内毒素血症发挥保护肝脏及小肠的作用,为治疗梗阻性黄疸患者提供了一种新的思路和方法.

Abstract：

Objective To evaluate the therapeutic effect and mechanism of specific inducible nitric oxide synthase(iNOS)aminoguanidine(AG)in rats with obstructive jaundice.Methods Forty male Wistar rats were divided randomly into four groups: normal control group, sham operation group, obstructive jaundice group and aminoguanidine therapeutic group.Each group had 10 rats.We assayed levels of liver function,hemobilirubin, endotoxin,lactic acid and malondialdehyde before and after therapy, and we also analyzed pathology of the liver and small intestine.Then we could explore the therapeutic effect of AG in rats with obstructive jaundice.Results The levels of endotoxin,lactic acid and malondialdehyde in blood increased progressively along with the pathological changes of the liver and small intestine.Each of the AG group parameters was significantly lower, and the pathological changes of liver and small intestine were improved.Conclusion AG could protect liver and small intestine by attenuating lipid peroxidative and endotoxemia,and provide a new way to cure obstructive jaundice.     

重组BPI对内毒素休克大鼠肝脏一氧化氮合酶和微循环灌注的影响

体外试验显示,杀菌/通透性增加蛋白(BPI)能与多种革兰氏阴性菌脂多糖分子结合,并抑制脂多糖诱导的细胞应答反应.我们新近的观察证实,重组BPI片段(rBPI21)能有效减轻内毒素休克时全身血流动力学紊乱及组织微循环障碍,但其确切的作用机理尚不清楚.本研究应用大鼠内毒素攻击模型,旨在探讨rBPI21对内毒素诱导肝组织一氧化氮合酶(NOS)和局部微循环灌注的影响及其意义.大鼠腹腔注射大肠杆菌内毒素(15.0 mg/kg)复制内毒素休克模型,动物随机分为正常对照组(n=10)、内毒素休克组(简称休克组,n=20)和rBPI21治疗组(简称治疗组,n=20).治疗组动物于内毒素攻击后0.5、2小时静脉注射rBPI21(10.0mg/kg);休克组、治疗组动物分别于内毒素攻击后4、8小时活杀,留取肝组织标本检测NOS活性、三磷酸鸟苷环水解酶I(GTP-CHI)活性及生物喋呤含量,同时还观察肝脏微循环血流灌注量的改变.结果显示：(1)内毒素休克大鼠肝组织结构型NOS(cNOS)活性仅呈现升高趋势,但与对照组相比无明显差异(P＞0.05),而诱生型NOS(iNOS)活性则大幅度上升,内毒素攻击后8小时为基础值的13.5倍(P＜0.01).给予rBPI21治疗可有效抑制肝组织iNOS活性(P＜0.01),但对cNOS活性无明显影响(P＞0.05).(2)休克组肝脏微循环灌注量迅速下降,4、8小时分别为对照46.4％、35.3％(P＜0.01);治疗组动物肝脏微循环障碍明显改善,内毒素攻击后4小时其灌注量显著高于休克组(P＜0.01),8小时则趋于正常对照值.(3)治疗组局部组织GTP-CHI活性降低(P＜0.01),生物喋呤含量亦显著下降(P＜0.05).该结果表明：内毒素休克早期给予rBPI21能选择性抑制肝组织iNOS活性及改善局部微循环,其作用机理与降低组织GTP-CHI活性及其介导生物喋呤诱生有关.     

氨基胍在重度失血性休克中的应用研究

目的：研究氨基胍（AG）在重度失血性休克中的治疗效果。方法：采用兔失血性休克－复苏模型,分为休克组,AG组（复苏时应用AG）,观察休克前后血浆内毒素（ET）,肿瘤坏死因子（TNF）－α,白细胞介素（IL）－6,IL－8,一氧化氮（NO）的变化,观察动物24,48h存活率。结果：兔失血性休克后,血浆内毒素,TNF－α,IL－6,IL－8,NO水平明显升高;复苏后,AG组动物血浆中上述物质水平明显低于休克组,该组动物的存活率明显高于休克组。结论：内毒素血症,TNF－α,IL-6,IL-8,NO在失血性休克的发展过程中起着重要作用,AG作为诱导型一氧化氮合酶（iNOS)抑制剂,有助于改善重度失血性休克的预后。     

大鼠移植肝组织中一氧化氮合酶的表达及其抑制剂的作用

目的 观察大鼠移植肝组织中一氧化氮合酶(iNOS)的表达及iNOS抑制剂氨基胍和免疫抑制剂他克莫司(FK-506)对肝移植术后急性排斥反应的影响。方法 实验分为4组：同基因组(供、受者均为LEW大鼠)；急性排斥组(供者为BN大鼠，受者为LEW大鼠)；氨基胍组、FK506组在异基因大鼠肝移植后分别应用氨基胍和FK506。用免疫组织化学法检测各组移植肝组织中iNOS表达水平。结果 急性排斥组iNOS表达呈强阳性，与氨基胍组、FK506组、同基因组比较，差异显著。结论 在大鼠原位肝移植发生急性排斥反应时，iNOS增高程度与排斥反应的强度有明显关系。氨基胍和FK506可以抑制iNOS的表达，明显减轻移植肝组织的急性排斥反应。     

川芎嗪联合氨胍对糖尿病大鼠肾脏一氧化氮的影响

目的：探讨川芎嗪联合氨胍对糖尿病肾脏病变的保护作用及其机制。方法：用链脲佐菌素制作糖尿病大鼠模型，分为正常对照组、糖尿病模型组、川芎嗪治疗组、氨胍治疗组和川芎嗪联合氨胍治疗组，于第12周测定各组大鼠肾组织一氧化氮合酶的活性和一氧化氮含量。结果：川芎嗪联合氨胍治疗纪、川芎嗪治疗组、氨胍治疗组大鼠肾组织NOS活性显高于模型组(P＜0．01)，NO的含量增加(P＜0．01)。川芎嗪治疗组、氨胍治疗组NOS活性低于正常对照组(P＜0．01)，NO的合量降低(P＜0．01)；川芎嗪合氨基胍治疗组与正常组相比无差异。结论：川芎嗪联合氨基胍能够增强糖尿病大鼠肾组织NOS活性，增加NO的含量，从而对糖尿病性肾病起一定治疗作用。     

Effective inhibition of nitric oxide production by aminoguanidine does not reverse hypotension in endotoxaemic rats

BACKGROUND: Excess production of nitric oxide (NO) by the inducible NO synthase (iNOS) has been implicated in the pathophysiology of septic shock. Using methaemoglobin (metHb) and the stable NO metabolite nitrate as markers of NO formation, we assessed the effect of iNOS blockade by aminoguanidine (AG) on hypotension and NO formation in endotoxaemic rats. METHODS: In 32 male Wistar rats under chloralose anaesthesia, MetHb (at 15 and 330 min, respectively) and plasma nitrate (at 330 min) were determined. Mean arterial pressure, heart rate and haematocrit were monitored. The LPS group (n=8) received bacterial endotoxin (LPS), 3 mg kg(-1) i.v. and was subsequently monitored for 5 h. At 2 h after LPS, the LPS+AG20 group (n=8) received AG, 5 mg kg(-1), and 5 mg kg(-1) h(-1) for the remaining 3 h. The LPS+AG100 group (n=8) instead received 25 mg kg(-1), followed by 25 mg kg(-1) h(-1). The NaCl group (n=8) was given corresponding volumes of isotonic saline. RESULTS: AG decreased the LPS-induced rise in plasma nitrate by about 50% in the LPS+AG20 group. MetHb levels, however, were not appreciably reduced by this dose. Both NO metabolites reached control levels after the higher dose of AG. LPS caused a progressive decrease in haematocrit. AG did not influence the LPS-induced hypotension, tachycardia or haemodilution. CONCLUSION: AG inhibited NO formation in a dose-dependent way. Yet, AG had no haemodynamic effects, suggesting a minor cardiovascular influence of iNOS in this endotoxin model, in parallel to what has been found in microbial sepsis.     

诱导性一氧化氮合酶抑制药对感染性休克鼠肝、肺组织学改变的影响

目的　研究诱导性一氧化氮合酶 ( i NOS)抑制药氨基胍 ( AG)和非选择性 NOS抑制药L- N-硝基精氨甲酯 ( L- NAME)对感染性休克鼠肝肺组织学改变的影响。方法　小鼠腹腔内注射 ( i.p.)内毒素 ( L PS,2 0 mg· kg- 1 )后 4小时随机分为 L PS组 ( n=60 ) ,L PS L - NAME组 ( 3 0 mg· kg- 1i.p.,n=60 )。和 L PS AG组 ( 2 0 mg· kg- 1 i.p.,n=60 )。5小时后取受试鼠的肝肺组织进行光镜和电镜检查。并观察 2 4小时内受试鼠的生存率。结果　 L PS组、L PS L- NAME组和 L PS AG组 2 4小时内生存率分别为 3 7.5 % ,5 %和 64 .3 % ( P<0 .0 5 )。光镜下 L PS组和 L PS L- NAME组肝细胞和核肿胀 ;肺间质增厚。电镜下可见 L PS组和 L PS L- NAME组可见肝细胞核、细胞膜和线粒体膜明显破坏 ;肺血气屏障明显增厚。 L PS AG组肝细胞和肺部的改变明显轻于其它两组。结论　感染性休克中 c NOS介导的一定量的 NO对器官有保护作用。以氨基胍选择性抑制 i NOS合成的 NO,疗效好于非选择性 NOS抑制药     

The role of selective nitric oxide synthase inhibitor on nitric oxide and PGE2 levels in refractory hemorrhagic-shocked rats

BACKGROUND: The up-regulation of nitric oxide (NO) and cyclooxgenase-2 (COX-2) has been implicated in the pathophysiology of hemorrhagic shock. We examined the effects of aminoguanidine (AG), which is a known inducible nitric oxide synthase (iNOS) inhibitor, and NS-398, a known COX-2 inhibitor, in our rat model of refractory hemorrhagic shock (RHS). MATERIAL AND METHODS: We measured tissue iNOS and COX-2 protein expression, brain and plasma nitrate/nitrite and prostaglandin E2 (PGE2) levels, plasma creatinine and glutamic oxalacetic transaminase (GOT) levels, quantified the histological damages in kidney, liver, lung, and brain, survival rate, and mean arterial blood pressure (MABP) in RHS rats. RESULTS: Semiquantitative analysis of tissues showed iNOS protein was not detected in AG + RHS rats but was detected in normal saline and NS-398 RHS rats. Tissue COX-2 protein was not detected in AG and NS-398 RHS rats but was detected in normal saline + RHS rats. The levels of brain and plasma nitrate/nitrite and PGE2 and plasma creatinine and GOT were significantly lower in the AG + RHS rat group when compared with the normal saline RHS rat group. Histological examinations also showed a reduction in organ damage for AG + RHS rats when compared with treated RHS rats. AG + RHS rats showed significantly increased survival and MABP level when compared with treated RHS rats. CONCLUSION: Our present findings suggest that NO produced by iNOS might result in organ damages. This in turn might lead to COX-2 up-regulation, and it increases the production of reactive oxygen species and toxic prostanoids. NO-mediated organ damage might be one way in which toxic products of COX-2 might further contribute to NO's deleterious effect in the later stages of RHS. It is therefore suggested that treatment of AG via inhibition of NO might contribute to improved physiological parameters and survival rates following RHS.     

The Effect of Aminoguanidine on Blood and Tissue Lipid Peroxidation in Jaundiced Rats With Endotoxemia Induced With LPS

Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO^?) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na⁺/K⁺-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.     

The effect of aminoguanidine on blood and tissue lipid peroxidation in jaundiced rats with endotoxemia induced with LPS.

Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO(-)) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na(+)/K(+)-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.     

诱导性一氧化氮合酶在大鼠肝缺血再灌注损伤中的作用

目的 探讨诱导性一氧化氮合酶（iNOS）在大鼠部分肝缺血再灌注损伤中的作用.方法 选取雄性Sprague-Dawley大鼠30只,体重225～250 g,随机分成氨基胍（AG）组、脂多糖（LPS）组、对照组.每组均按相同方法建立70%的肝缺血再灌注损伤模型（缺血1 h,再灌注6 h）,取再灌注大鼠肝组织及血清样本.氨基胍（AG）组（n=10）：术前30 min尾静脉注射AG 100 mg/kg（质量浓度10 kg/L）;脂多糖（LPS）组（n=10）：术前30 min尾静脉注射LPS 10 mg/kg（质量浓度1 kg/L）;对照组（n=10）：术前30 min尾静脉注射生理盐水（10 μL/kg）.检测血清谷氨酸转氨酶（ALT）水平,实时荧光定量PCR测定肝组织iNOS mRNA的表达,Western blot测定肝组织iNOS蛋白的表达,考马斯法测定肝组织匀浆丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性,HE染色光镜下组织学观察等.结果 AG组与对照组相比,肝组织中iNOS mRNA表达量明显下降（P〈0.05）,iNOS蛋白表达量明显下降（P〈0.05）;ALT和MDA明显下降（P〈0.05）;SOD明显升高（P〈0.05）;肝细胞水肿较轻,排列相对整齐.LPS组与对照组相比,肝组织中iNOS mRNA表达量明显升高（P〈0.05）,iNOS蛋白表达量明显升高（P〈0.01）;ALT和MDA明显升高（P〈0.05）;SOD则明显降低（P〈0.05）;肝细胞水肿,排列紊乱,并且出现水样变性.结论 iNOS 升高会加重缺血再灌注损伤,这一过程可能通过改变氧化还原状态实现.