Role of interleukin 18 in acute lung inflammation induced by gut ischemia repeifusion

AIM: To study the changes of endogenous interleukin 18 (IL-18) levels and evaluate the role of IL-18 on lung injury following gut ischemia/reperfusion. METHODS: A superior mesenteric artery occlusion model was selected for this research. The mice were randomly divided into four groups: Sham operation (sham), ischemia (0.5 h) followed by different times of reperfusion (I/R), and I/R pretreated with exogenous IL-18 (I/R+IL-18) or IL-18 neutralizing antibody (I/R+IL-18Ab) 15 min before ischemia. Serum IL-18 levels were detected by Western blot and ELISA, and the levels of IL-18 in lung tissue were evaluated by immunohistochemical staining. For the study of pulmonary inflammation, the lung myeloperoxidase (MPO) contents and morphological changes were evaluated. RESULTS: Gut ischemia/reperfusion induced rapid increase of serum IL-18 levels, peaked at 1 h after reperfusion and then declined. The levels of IL-18 in lung tissue were gradually enhanced as the progress of reperfusion. Compared with I/R group, exogenous administration of IL-18 (I/R+IL-18) further remarkably enhanced the pulmonary MPO activity and inflammatory cell infiltration, and in I/R+IL-18Ab group, the content of MPO were significantly reduced and lung inflammation was also decreased. CONCLUSION: Gut ischemia/reperfusion induces the increase of IL-18 expression, which may make IL-18 act as an important proinfiammatory cytokine and contribute to gut ischemia/reperfusion-induced lung inflammation.     

Mannitol dose-dependently attenuates lung reperfusion injury following liver ischemia reperfusion: a dose-response study in an isolated perfused double-organ model

Abstract We had previously studied different modes of prevention of liver ischemia-reperfusion (IR)-induced remote organ reperfusion injury, a challenge that remains partly unmet. We have now studied the capability of mannitol at different doses in abrogating liver IR-induced lung reperfusion injury in an isolated double-organ model. Rat livers (n = 8/group) were perfused with Krebs-Henseleit solution (control) or made globally ischemic (IR) for 2 h, after which they were paired with normal lungs and “reperfused” together for 15 min. The lungs were then perfused alone with the accumulated Krebs for an additional 45 min. Another 4 control and 4 IR pairs were reperfused with Krebs containing mannitol at .22 mmol, .55 mmol, .77 mmol, or 1.1 mmol. Mannitol .22 mmol and 1.1 mmol failed to attenuate IR-lung injury as indicated by 50–95% increases in inspiratory and perfusion pressures and compliance reduction, a 70% increase in weight gain, and a 2–50-fold increase in bronchoalveolar lavage volume and content. Mannitol .55 mmol prevented all these abnormalities, and .77 mmol attenuated only changes in ventilatory parameters. The latter two treatments were also associated with a 50% reduction in xanthine oxidase activity and a 35–45% increase in the reduced glutathione tissue content compared with the nontreated IR-paired lungs. It is concluded that mannitol in a narrow therapeutic dose range can reduce oxidalive stress-induced lung damage that is related to liver IR.     

Thrombin increases cardiomyocyte acute cell death after ischemia and reperfusion

Thrombin exerts multiple actions on cardiomyocytes leading to increased intracellular Na+ and Ca2+ concentrations, and to activation of a Ca2+-independent PLA2, and has been proposed to favor the genesis of arrhythmias and ischemic injury in acute coronary syndromes. However, the influence of thrombin on cardiomyocyte cell death during ischemia-reperfusion has not been studied. A beneficial influence of low thrombin concentrations has been described in other cell types. HL-1 cardiomyocytes were subjected to simulated ischemia (SI) and reperfusion (SR) and cell death was assessed by means of LDH release to the incubation media. Thrombin dose-dependently increased cell death in normoxic cells, in cells subjected to SI, and in cells subjected to SR (by 20+/-8%, 95+/-32% and 35+/-9%, respectively, at 100 U/ml). The effects of thrombin were associated to increased cytosolic Ca2+ overload, mimicked by 100 microM PAR-1 agonist peptide SFLLRNPNDKYEPF, and reversed by the direct thrombin inhibitor lepirudin (IC50=1.3+/-0.2 microg/ml). The presence of thrombin during simulated ischemia-reperfusion increases cardiomyocyte cell death by a mechanism that involves activation of PAR-1 receptors and can be prevented by the direct thrombin inhibitor lepirudin.     

Redox therapeutics in hepatic ischemia reperfusion injury

Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.     

Redox therapeutics in hepatic ischemia reperfusion injury简

Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.     

L-nitro-arginine inhibits increase in endothelin binding sites induced by ischemia and reperfusion

We have demonstrated that ischemia and reperfusion promoted augmented contractile response to endothelin-1 (ET) in coronary arteries in the presence of polymorphonuclear leukocytes (PMN). It has been also reported that ischemia and reperfusion increase ET binding sites in cardiac membrane in isolated rat heart perfused by blood cell-free system. To determine the role of PMN and L-arginine to nitric oxide (NO) pathway in these phenomena, isolated perfused rabbit hearts were subjected to 30 min of global ischemia followed by 30 min of reflow in the absence or presence of PMN and 10(-5)M of L-nitro-arginine (LNA). PMN was prepared with Percoll density gradients from peritoneal exudate elicited by glycogen. PMN activated with 10(-6)M of phorbol myristate acetate or their supernatant were infused into the coronary perfusion circuit after 5 min of reflow. LNA was added to perfusate also after reflow. The effect of superoxide dismutase (SOD: 50 IU/ml) was also determined. After the end of protocols, membrane fraction was isolated from the hearts for (125)I-ET-1 binding assay. ET-1 binding (Bmax) showed a significant increase by ischemia and reperfusion (P<0.01 vs control). That was markedly augmented with addition of activated PMN or their supernatant (both P<0.01), but abolished either by LNA or SOD (P<0.01 and P<0.05, respectively). These results indicate that increase in ET-receptor by ischemia and reperfusion is mediated by free radicals generated via L-arginine to NO pathway.     

Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion

AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.     

老年大鼠脑缺血再灌注神经肽的变化及其意义

目的 从内皮素（ET）、降钙素基因相关肽（CGRP）、神经肽Y（NPY）、神经降压素（NT）的变化方面研究老年大鼠脑缺血再灌注损伤的机制。方法 青年（5月龄）和老年（20月龄以上）大鼠均分为模型组和正常对照组，观察大鼠全脑缺血30min再灌注60min后血浆和脑组织中ET、CGRP、NPY、NT含量。结果 老年对照组和青年模型组血浆CGRP低于青年对照组（P＜0．01），老年模型组血浆ET含量高于老年对照组和青年模型组。与青年对照组和老年模型组比较，老年对照组脑组织CGRP含量增高而ET和NPY含量降低。青年对照组血浆中NT高于老年对照组和青年模型组。结论 脑缺血再灌注损伤与CGRP－ET和NPY－NT的平衡失调有关。老年大鼠脑缺血再灌注病理改变血浆中以ET占优势，脑组织中以NPY和ET占优势。     

Glyceraldehyde phosphate dehydrogenase oxidation during cardiac ischemia and reperfusion

OBJECTIVES: Protein S-glutathiolation is a predicted mechanism by which protein thiol groups are oxidized during the oxidative stress of ischaemia and reperfusion. We measured protein S-thiolation during ischaemia and reperfusion and investigated the effect of this oxidative modification on the function of GAPDH. METHODS: Glutathione was biotinylated (biotin-GSH) and used to probe for protein S-glutathiolation in isolated rat hearts using non-reducing Western blots and streptavidin-HRP. Streptavidin-agarose was used to purify S-glutathiolated proteins and these were identified using N-terminal sequencing and database searching. RESULTS: Little protein S-glutathiolation occurred in control preparations, but this increased 15-fold during reperfusion. Protein S-glutathiolation was attenuated by the antioxidant mercaptopropionylglycine and was shown to occur only during the firstminutes of reperfusion. Affinity purification of the S-glutathiolated proteins showed 20 dominant S-glutathiolation substrates. A dominant S-thiolated protein was N-terminally sequenced (VKVGVNGFG) and HPLC peptide mapping gave additional sequence nearer the site of oxidation (TGVFTTMEKA). The first sequence was the N-terminus of GAPDH, and the second a peptide from the same protein starting at residue 96. GAPDH was immunopurified from aerobic, ischemic or reperfused hearts. Maleimidofluorescein labeling of purified GAPDH provided an index of its reduced thiol status. In the absence of DTT, ischemia induced a reduction in the number of free thiols on GAPDH that was reversed on reperfusion. When treated with DTT, the free thiol status of GAPDH could be increased in ischemic but not reperfused samples. Ischemia induced a reduction in GAPDH activity that was partially restored by reperfusion. DTT-treatment reactivated ischemic GAPDH, but had little effect on the activity from reperfused tissue. Mass spectra acquired from aerobic GAPDH preparations were relatively simple whereas spectra from ischemic or reperfused preparations were highly complex, possibly indicative of oxidation by multiple oxidants. CONCLUSIONS: Many proteins, including GAPDH, are targets for S-glutathiolation during cardiac oxidative stress. GAPDH oxidation is associated with a loss in reduced cysteine status that correlates with the inactivation of this enzyme.     

陷窝蛋白-1与脑缺血后炎性反应

陷窝蛋白-1作为陷窝的标志蛋白,通过其脚手架结构域寡聚许多细胞信号转导分子,参与许多病理生理过程,也通过不同的途径调控脑缺血后炎症反应。文章对近年来陷窝蛋白-1与缺血性卒中后炎性反应相关研究进展进行了回顾,重点讨论其炎症调控机制。     

The effect of ischemia and reperfusion on sarcolemmal function in perfused canine hearts

The report deals with the effect of ischemia and reperfusion on purified sarcolemma obtained from canine myocardium of perfused supported heart preparations. Perfusion was carried out with a perfluorochemical (FC-43). Ischemia was produced by intermittent total clamping of inflow and outflow followed by release until the decrease in dP/dtmax had become stabile. Purity of sarcolemmal vesicles was ascertained with marker enzymes: succinate cytochrome c reductase (for mitochondria), K+-stimulated p-nitrophenylphosphate (K+-pNPPase), (Na+/K+)ATPase and adenylate cyclase (for SL). In addition Na+/Ca2+-exchange characteristics for SL were determined. Sidedness of vesicles was ascertained by means of adenylate cyclase activity using sarcolemmal preparations treated and untreated with alamethicin. Emphasis was placed on ATP-dependent Ca2+ uptake, phosphorylation of sarcolemmal vesicles and yield of SL proteins. Ischemia and reperfusion resulted in a significant reduction in adenylate cyclase activity. This decline was significant following ischemia and reperfusion. The yield of protein recovered from SL vesicles from ischemic-reperfused heart preparations was also significantly decreased. Both initial rate of ATP-dependent Ca2+ uptake and maximal Ca2+ uptake fell significantly following ischemia and reperfusion. The initial rate of phosphorylation also dropped significantly. These disturbances in SL Ca2+ transport following ischemia and reperfusion are probably a part of the general deficit in Ca2+ translocation.     

Myocardial protection by co-administration of l-arginine and tetrahydrobiopterin during ischemia and reperfusion

Background

Reduced bioavailability of nitric oxide (NO) is a key factor contributing to myocardial ischemia and reperfusion injury. The mechanism behind the reduction of NO is related to deficiency of the NO synthase (NOS) substrate l-arginine and cofactor tetrahydrobiopterin (BH₄) resulting in NOS uncoupling. The aim of the study was to investigate if the combination of l-arginine and BH₄ given iv or intracoronary before reperfusion protects from reperfusion injury.

Methods

Sprague–Dawley rats and pigs were subjected to myocardial ischemia and reperfusion. Rats received vehicle, l-arginine, BH₄, l-arginine + BH₄ with or without the NOS-inhibitor L-NMMA iv 5 min before reperfusion. Pigs received infusion of vehicle, l-arginine, BH₄ or l-arginine + BH₄ into the left main coronary artery for 30 min starting 10 min before reperfusion.

Results

Infarct size was significantly smaller in the rats (50 ± 2%) and pigs (54 ± 5%) given l-arginine + BH₄ in comparison with the vehicle groups (rats 65 ± 3% and pigs 86 ± 5%, P < 0.05). Neither l-arginine nor BH₄ alone significantly reduced infarct size. Administration of L-NMMA abrogated the cardioprotective effect of l-arginine + BH₄. Myocardial BH₄ levels were 3.5- to 5-fold higher in pigs given l-arginine + BH₄ and BH₄ alone. The generation of superoxide in the ischemic-reperfused myocardium was reduced in pigs treated with intracoronary l-arginine + BH₄ versus the vehicle group (P < 0.05).

Conclusion

Administration of l-arginine + BH₄ before reperfusion protects the heart from ischemia–reperfusion injury. The cardioprotective effect is mediated via NOS-dependent pathway resulting in diminished superoxide generation.     

Effects of N-acetylcysteine and pentoxifylline on remote lung injury in a rat model of hind-limb ischemia/reperfusion injury

Objective

: To investigate the effects of N-acetylcysteine (NAC) and pentoxifylline in a model of remote organ injury after hind-limb ischemia/reperfusion (I/R) in rats, the lungs being the remote organ system.

Methods

: Thirty-five male Wistar rats were assigned to one of five conditions (n = 7/group), as follows: sham operation (control group); hind-limb ischemia, induced by clamping the left femoral artery, for 2 h, followed by 24 h of reperfusion (I/R group); and hind-limb ischemia, as above, followed by intraperitoneal injection (prior to reperfusion) of 150 mg/kg of NAC (I/R+NAC group), 40 mg/kg of pentoxifylline (I/R+PTX group), or both (I/R+NAC+PTX group). At the end of the trial, lung tissues were removed for histological analysis and assessment of oxidative stress.

Results

: In comparison with the rats in the other groups, those in the I/R group showed lower superoxide dismutase activity and glutathione levels, together with higher malondialdehyde levels and lung injury scores (p < 0.05 for all). Interstitial inflammatory cell infiltration of the lungs was also markedly greater in the I/R group than in the other groups. In addition, I/R group rats showed various signs of interstitial edema and hemorrhage. In the I/R+NAC, I/R+PTX, and I/R+NAC+PTX groups, superoxide dismutase activity, glutathione levels, malondialdehyde levels, and lung injury scores were preserved (p < 0.05 for all). The differences between the administration of NAC or pentoxifylline alone and the administration of the two together were not significant for any of those parameters (p > 0.05 for all).

Conclusions

: Our results suggest that NAC and pentoxifylline both protect lung tissue from the effects of skeletal muscle I/R. However, their combined use does not appear to increase the level of that protection.     

Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats

AIM: To investigate the effects of Cromolyn Sodium (CS) pretreated prior to reperfusion on the activity of intestinal mucosal mast cells (IMMC) and mucous membrane of the small intestine in ischemia-reperfusion (IR) injury of rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups: sham group (group S), model group (group M), high and low dosage of CS groups, (treated with CS 50 mg/kg or 25 mg/kg, group C1 and C2). Intestinal IR damage was induced by clamping the superior mesenteric artery for 45 min followed by reperfusion for 60 min. CS was intravenouly administrated 15 min before reperfusion. Ultrastructure and counts of IMMC, intestinal structure, the expression of tryptase, levels of malondisldehyde (MDA), TNF-α, histamine and superoxide dismutase (SOD) activity of the small intestine were detected at the end of experiment. RESULTS: The degranulation of IMMC was seen in group M and was attenuated by CS treatment. Chiu’s score of group M was higher than the other groups. CS could attenuate the up-regulation of the Chiu’s score, the levels of MDA, TNF-α, and expression of tryptase and the down-regulation of SOD activity and histamine concentration. The Chiu’s score and MDA content were negatively correlated, while SOD activity was positively correlated to the histamine concentration respectively in the IR groups. CONCLUSION: Pretreated of CS prior to reperfusion protects the small intestine mucous from ischemia- reperfusion damage, the mechanism is inhibited IMMC from degranulation.     

缺血后处理减轻大鼠肥厚心肌缺血再灌注损伤的观察

目的探讨缺血后处理对心肌肥厚大鼠离体心脏缺血再灌注损伤的影响及其信号机制。方法通过腹主动脉结扎建立大鼠心肌肥厚模型,用Landendorff装置建立心肌肥厚大鼠离体心脏缺血再灌注模型。观察缺血后处理对心肌肥厚大鼠离体缺血再灌注心脏左心室收缩压,冠状动脉流量,肌酸磷酸激酶和乳酸脱氢酶释放,心肌梗死范围,心肌组织中蛋白激酶B／Akt（Akt）、糖原合成酶激酶-3β（GSK-3β）磷酸化的影响。结果与缺血再灌注对照组相比,缺血后处理组心脏左心室收缩压、冠状动脉流量显著高,冠状动脉循环流出液中肌酸磷酸激酶、乳酸脱氢酶含量低,心肌梗死范围减小,心肌组织中磷酸化Akt（Ser473）、磷酸化GSK-3β（Set9）水平高,磷脂酰肌醇-3激酶（PI3K）抑制剂渥曼青霉素（wortmannin）能够抑制缺血后处理所致的磷酸化Akt（Ser473）、磷酸化GSK-3β（Set9）水平升高,但只能部分消除缺血后处理的心脏保护效应。结论缺血后处理能够减轻心肌肥厚大鼠离体心脏缺血再灌注损伤,PI3K／Akt／GSK-3信号途径参与介导缺血后处理对离体缺血再灌注肥厚心肌的保护作用。     

Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats

AIM： To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats. METHODS： Thirty male Wistar rats weighing 200-250 g were used. Ischemia was induced by obstructing blood flow in 25% of the total small intestinal length （ileum） with a vascular clamp for 45 min, after which either 60 min or 24 h of reperfusion was allowed. Rats were either anesthetized with pento-barbital sodium （50 mg/kg） or ketamine （100 mg/kg）. Control groups received sham surgery. After 60 min of reperfusion, the intestine was examined for mor-phological alterations, and after 24 h intestinal basic electrical rhythm （BER） frequency was calculated, and intestinal transit determined in all groups. RESULTS： The intestinal mucosa in rats that were anesthetized with ketamine showed moderate alterations such as epithelial lifting, while ulceration and hemorrhage was observed in rats that received pento-barbital sodium after 60 min of reperfusion. Quantitative analysis of structural damage using the Chiu scaleshowed significantly less injury in rats that received ketamine than in rats that did not （2.35 ± 1.14 vs 4.58 ± 0.50, P 〈 0.0001）. The distance traveled by a marker, expressed as percentage of total intestinal length, in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ± 1.64% in rats that received ketamine （P = 0.017）. BER was not statistically different between groups. CONCLUSION： Our results show that ketamine anesthesia is associated with diminished intestinal injury and abolishes the intestinal transit delay induced by ischemia/reperfusion.     

The effects of dietary hempseed on cardiac ischemia/reperfusion injury in hypercholesterolemic rabbits

BACKGROUND: Hempseed is a novel functional food that contains several health-promoting polyunsaturated fatty acids (PUFAs). PUFAs, such as those found in flaxseed and fish, have been shown to protect the heart against arrhythmias following ischemia/reperfusion. OBJECTIVE: TO INVESTIGATE THE POTENTIAL OF DIETARY HEMPSEED AS A CARDIOPROTECTIVE AGENT AGAINST GLOBAL ISCHEMIA AND SUBSEQUENT REPERFUSION BY ASSESSING SEVERAL MEASUREMENTS OF CARDIAC PERFORMANCE: QT interval duration, left ventricular pressure, arrhythmia incidence and arrhythmia duration. METHODS: MALE NEW ZEALAND WHITE RABBITS WERE FED ONE OF SIX DIETS: a control diet; or one supplemented with 10% hempseed, 10% delipidated hempseed, 0.5% cholesterol, 0.5% cholesterol plus 10% hempseed or 5% coconut oil. After eight weeks on their respective diets, the hearts were excised and subjected to 30 min of global ischemia and 45 min of reperfusion. Electrocardiogram traces were recorded throughout the experiment and were subsequently analyzed for QT interval duration, left ventricular pressure, arrhythmia incidence and arrhythmia duration. Plasma and cardiac tissue were analyzed for fatty acid content and composition. RESULTS: Cholesterol-fed animals exhibited significantly higher PUFA levels in their plasma, but this did not directly translate into higher PUFA levels in their cardiac fractions. There were no significant differences among the groups in the incidence or duration of ischemia-derived arrhythmias. During reperfusion, there was a significant decrease in the incidence of fibrillation in the hearts obtained from cholesterol-fed and hempseed- plus cholesterol-fed rabbits compared with the hearts from delipidated hempseed-fed rabbits. CONCLUSIONS: Dietary hempseed induced limited beneficial effects on cardiac function during ischemia/reperfusion challenge. The present study does not support the use of dietary hempseed to protect the heart during ischemic insult in this experimental model.     

微小RNA在心肌缺血再灌注损伤中的作用及机制

微小RNA（microRNA,miRNA）是一类在进化上高度保守的小分子非编码RNA,大约南19～25个核苷酸组成,具有转录后渊控蛋白质编码基因表达的功能,     

犬急性肺缺血再灌注损伤的病理学改变及中药814的干预作用

目的 :探讨肺缺血再灌注损伤的病理学改变及中药 814的干预作用。方法 :7只杂种犬随机分两组 :①急性肺缺血再灌注组 (3只 ) :结扎左主肺动脉 2 4h后恢复血流 4h ;②中药 814干预组 (4只 ) :再灌注前予中药 814腹腔注射 ,应用光镜和电镜等病理检测方法观察缺血期、再灌注期、中药 814干预后肺组织病理形态学改变 ,计算受损肺泡百分率。结果 :①急性肺缺血再灌注组 :缺血期 ,左肺散在出血 ,部分肺泡上皮细胞及肺血管内皮细胞胞质肿胀、线粒体空泡化、内质网扩张 ;同例对照右肺基本正常。再灌注期 ,左肺出血加重 ,肺间质及广泛肺泡腔内有水肿液 ,受损肺泡百分率显著增加 ,肺泡上皮细胞和肺血管内皮细胞肿胀、线粒体空泡化及嵴溶解加重 ,可见细胞坏死 ;同例对照右肺大致正常或散在小灶性肺泡腔内有水肿和出血 ,少数肺泡上皮细胞和肺血管内皮细胞轻度线粒体肿胀和空泡化。②中药 814干预组 :再灌注期左肺受损肺泡百分率显著减少 ,少数肺泡上皮细胞和肺血管内皮细胞线粒体轻度肿胀和空泡化。结论 :急性缺血后再灌注肺组织病理学形态显示比较明显的损伤 ,中药 814对再灌注肺损伤有一定的实验防治作用