Muscle cells become necrotic rather than apoptotic during reperfusion of ischaemic skeletal muscle

While necrosis is known as a major mechanism for the loss of viability of skeletal muscle following ischaemia and reperfusion, much less is known of the role of apoptosis. In this study rat hind limbs were subjected to 2 h of tourniquet ischaemia, then reperfused for either 0, 0.25, 0.5, 1, 3, 8, 16 or 24 h (n = 6 per group). Mean viability of muscle, assessed by tetrazolium dye reduction, after 2 h ischaemia and 24 h reperfusion was 17%. Histological examination revealed disrupted, necrotic muscle fibres from 30 min to 24 h reperfusion. Apoptotic nuclei were identified by haematoxylin staining and TUNEL, terminal deoxynucleotidyl transferase mediated dUTP nick end labelling. No TUNEL-positive cells were observed at the end of the ischaemic period, but a small number of TUNEL-positive endothelial and smooth muscle cells were found at 30 min reperfusion, with a progressive increase in their number up to 24 h reperfusion. Apoptotic neutrophils were detected after 8-24 h reperfusion. At no stage was apoptosis seen in the nuclei of skeletal muscle fibres. It appears that apoptosis plays no role in the death of muscle fibres after ischaemia-reperfusion injury to skeletal muscle.     

Ischaemia-induced injury in glycogen-depleted skeletal muscle. Selective vulnerability of FG-fibres

The effect of preischaemic glycogen-depletion on the development of skeletal muscle injury was investigated in rats subjected to tourniquet hind-limb ischaemia. Glycogen depletion was performed by direct electrical stimulation of the extensor digitorum longus (EDL) muscle during ischaemic conditions. The metabolite load during the subsequent 2.5 h of ischaemia was modified by allowing, or not allowing, a short reperfusion period after termination of the electrical stimulation. The extent of injury was evaluated morphologically after 5 or 15 h of reperfusion, by the combination of an intravital dye exclusion test and a histochemical staining, demonstrating calcium-precipitates-Alizarin red S. Minimal damage was found in animals subjected to ischaemia without preceding glycogen depletion. In both groups of preischaemically glycogen-depleted animals, significant irreversible injury occurred. The injury was significantly less in animals in which a wash-out period was allowed after termination of stimulation. Fast-glycogenolytic fibres (FG) were most sensitive to the ischaemic insult during both experimental conditions, while slow-oxidative fibres (SO) were spared. Fast-oxidative-glycogenolytic fibres (FOG) showed an intermediate response. The injury seemed to be established after 5 h of reperfusion, indicating that cells react with an all-or-nothing response in the present model.     

Protective effects of N-acetylcysteine on myocardial injury induced by hindlimb ischaemia–reperfusion: a histological study in a rat model

This study evaluated the effects of N-acetylcysteine as a scavenger of radical oxygen species on myocardial injury as a remote organ after skeletal muscle ischaemia–reperfusion. Twenty male Wistar rats were allocated randomly into two experimental groups: ischaemia–reperfusion and ischaemia–reperfusion?+?N-acetylcysteine. All animals underwent 2 h of ischaemia by occlusion of the femoral artery followed by 24 h of reperfusion. Rats treated with N-acetylcysteine were given an intravenous dose of 150 mg/kg, immediately before reperfusion. After the reperfusion period, animals were euthanized and hearts harvested for histopathological analysis under light microscopy. In the ischaemia–reperfusion group, tissues showed histological changes with interstitial oedema, neutrophil infiltration and adhesion of neutrophils to the endothelium, haemorrhage and coagulative necrosis. Histopathologically, there was a significant difference (P?N-acetylcysteine significantly decreased myocardial injury induced by skeletal muscle ischaemia–reperfusion according to our histological findings.     

No protection of the porcine kidney by ischaemic preconditioning

One or more episodes of sublethal ischaemia and reperfusion delay infarct development during subsequent, sustained ischaemia in the heart and skeletal muscle. The present study tested whether or not such ischaemic preconditioning (IP) also protects the kidney. Enflurane-anaesthetized pigs underwent 60 min of right renal vessel occlusion (RVO), followed by 8 h of reperfusion without (placebo group, n = 8) or with three preceding cycles of 10 min RVO and 10 min reperfusion (IP group, n = 8). After 8 h of reperfusion, kidneys were oliguric in both groups (placebo group: 23 +/- 21 ml x h(-1), IP group: 24 +/- 27 ml x h(-1)). A transient polyuric phase occurred in the IP group at 2 h reperfusion. The reperfused kidneys did not excrete inulin, creatinine or urea in both groups, although renal blood flow during reperfusion was similar to baseline. Morphological damage ranged in both groups from single cell necrosis to disseminated patchy necrosis; the number of pyknotic cells tended to be higher in the IP group than in the placebo group (27.0 +/- 7.1 vs. 15.6 +/- 5.6%, n.s.). In anaesthetized pigs, IP did not therefore attenuate renal dysfunction and morphological damage resulting from 60 min of renal normothermic ischaemia followed by 8 h of reperfusion.     

Neutrophil-independent protective effect of r-metHuG-CSF in ischaemia-reperfusion injury in rat skeletal muscle

The aim of this study was to investigate the effect of the cytokine, r-metHuG-CSF, in a rat model of ischaemia-reperfusion (IR) injury and the pathophysiological mechanism involved. The administration of r-metHuG-CSF (20 (g/kg, s.c.) 4 h prior to either 100 min or 2 h of tourniquet ischaemia to the upper thigh significantly improved the viability of skeletal muscle after 24 h reperfusion compared with saline-treated rats (P < 0.05). Administration of r-metHuG-CSF earlier (24 h before ischaemia) or later (immediately before ischaemia) had no protective effect. At the dose used, r-metHuG-CSF caused a three-fold increase in the level of circulating blood neutrophils and a modest but significant increase in the neutrophil content of ischaemic muscle after 24 h reperfusion. Reduction of neutrophils to 1.4% of normal levels by cyclophosphamide (150 mg/kg, i.p.) prior to injury had no significant effect on the survival of muscle subjected to 2 h ischaemia and 24 h reperfusion or on the protective effect of r-metHuG-CSF. IR injury to skeletal muscle was accompanied by a time-dependent increase in plasma TNFalpha levels during the first 8 h of reperfusion and the increase was reduced significantly by pretreatment with r-metHuG-CSF. However, a similar time-dependent increase in plasma nitrite/nitrate levels was unaffected by pretreatment with r-metHuG-CSF. These findings suggest that the protective effect of r-metHuG-CSF may be mediated by the attenuated release of TNFalpha and indicate that the level of neutrophils in either blood or injured tissue does not influence significantly the viability of rat muscle after IR injury.     

Abnormal mitochondria and sarcoplasmic changes in rabbit skeletal muscle induced by immobilization

Immobilization of the rabbit knee in extended position results in damage to the vastus intermedius profundus (VIP) muscle. To examine the mechanisms involved in initiation of the injury, we studied the light and electron microscopic morphology of the VIP muscle, as well as the activity and distribution of NADH tetrazolium reductase (NADH-TR) in the affected muscle, and determined serum total creatine kinase (CK) activity in immobilized rabbits. The VIP muscle of the immobilized right hindlimb was removed at various time points (10 h, 24 h, 36 h and 48-72 h, n=5 for each time point). The nonimmobilized left hindlimb and five nonimmobilized animals served as controls. No morphological changes were observed by light microscopy within 48-72 h in routine stainings. Transient ultrastructural abnormalities, including abnormal cristae, matrix lucencies and mild swelling of mitochondria, were observed between 10 h and 36 h of immobilization, subsiding by 48-72 h. On the other hand, progressive disorganization of myofibrils with breaking-up of Z-bands and an increase in the number and size of sarcoplasmic lipid vacuoles was seen with increasing duration of immobilization. NADH-TR activity at subsarcolemmal locations had decreased by 10 h and disappeared by 24 h of immobilization, while the intermyofibrillar mitochondria remained unaltered. Serum total CK activity began to increase by 2 h of immobilization and reached a peak by 24 h. The results indicate that already a few hours of immobilization of the rabbit knee in extension leads to signs of metabolic disturbance of the VIP muscle and sarcolemmal leakage. The simultaneous occurrence of transient mitochondrial abnormalities, transient CK efflux and progressive myofibrillar damage suggests the operation of multiple adverse mechanisms already at the onset of disuse muscle atrophy.     

Effects of running exercise with increasing loads on tibialis anterior muscle fibres in mice

Cross-sectional areas and succinate dehydrogenase (SDH) activities of type identified fibres in the deep, middle and superficial regions of the tibialis anterior muscle in mice were examined after 4 weeks of voluntary running exercise with increasing loads. Nineteen-week-old male mice were assigned randomly to either a control or exercise group. The mean cross-sectional areas of all types (IIa, IIx and IIb) of fibres in the superficial region of the muscle were greater in the exercise group than in the control group. The mean SDH activities of type IIx and type IIb fibres in the middle region and of all types (IIa, IIx and IIb) of fibres in the superficial region of the muscle were greater in the exercise group than in the control group. These results suggest that voluntary running exercise with increasing loads causes hypertrophy and/or an increase in the SDH activity of fibres in the specific muscle region where fibres with a high threshold and a low-oxidative enzyme activity are distributed, and these fibres are recruited to adapt to changes in exercise conditions.     

Fibre size and metabolic properties of myosin heavy chain-based fibre types in rat skeletal muscle

Cross-sectional area (CSA), succinate dehydrogenase (SDH), and -glycerophosphate dehydrogenase (GPD) activities were measured in single fibres of adult rat medial gastrocnemius muscle (deep region) using quantitative histochemical procedures. The same fibres were identified in serial sections stained by immunohistochemistry with monoclonal antibodies specific for selected myosin heavy chain (MyHC) isoforms. The values of CSA, SDH and GPD activities formed a continuum, but significant differences in mean values were observed among fibre types of presumed homogeneous MyHC content. Type IIA fibres were the smallest, type IIB fibres were the largest, and type I and IIX fibres were intermediate. Type IIA fibres had the highest SDH activity, followed in rank order by type IIX, type I and type IIB. The average GPD activity was ranked according to fibre type such that IIB>IIX>IIA>I. Hybrid fibres co-expressing two MyHC isoforms generally showed intermediate mean CSA, SDH a nd GPD values lying between their respective pure MyHC fibre types. Across all fibres, there was an inverse relationship between SDH activity and CSA and between GPD and SDH activities, and a positive correlation between GPD and CSA. Moreover, a significant interdependence between CSA, SDH activity, GPD activity and MyHC content existed on a fibre-to-fibre basis, suggesting that the MyHC isoform expressed in a fibre is associated with differences in size, oxidative and glycolytic capabilities of muscle fibres. In fact, most of the fibres could be discriminated into discrete groups with the same MyHC content when their CSA, SDH and GPD values were considered together.     

Immunohistochemical demonstration of migration inhibitory factor (MIF) in experimental allergic contact dermatitis.

The kinetics of appearance of MIF+ cells was investigated in experimental contact dermatitis using a monoclonal antibody (7D10) against murine MIF which was reacted with cryostat sections of tissues and detected by the indirect immunoperoxidase test. Four groups of BALB/c mice were investigated: (1) sensitized with 2,4-dinitrofluorobenzene (DNFB); (2) unsensitized controls; (3) tolerized; (4) unsensitized. A challenge dose of DNFB was applied to the ear of animals of groups 1-3 and of croton oil to those of group 4. Three phases could be distinguished in group 1: (a) an initial vascular and exudative reaction; (b) an early cellular phase; and (c) a late cellular phase. At zero time rarely any T lymphocytes (Lyt 1+; Lyt 2+) were seen in all four groups. Within less than 30 min venous endothelial cells became strongly MIF+. This was followed by an influx of monocytes/macrophages reaching a maximum of 72 h in group 1 and a slight peak at 12 h in groups 2 and 3. At 16-24 h in all groups the endothelial reaction weakened while many 7D10+ macrophages appeared in group 1. By double-labelling it was shown that lymphocytes were 7D10-. The influx of lymphocytes, part of which carried the T cell receptor, began at 12 h, reaching a maximum at 72 h in group 1. In groups 2 and 3 only a weak lymphocytic infiltrate developed which declined at 24 h. Group 4 developed an inflammatory reaction after the initial phase with similar kinetics as in group 1. The data suggest that an immune inflammatory reaction is preceded by a nonspecific reaction of the vascular endothelium and the mononuclear phagocytic system and that MIF is playing a central role in these events.     

Acute exhaustive exercise changes the metabolic profiles in slow and fast muscles of rat

The effects of acute endurance running on the metabolic profiles of rat skeletal muscle were studied. Male Wistar strain rats were continuously run on a treadmill for 1 h (speed, 35 m/min; grade, 0 degrees). Soleus (SOL) and extensor digitorum longus (EDL) were removed after 30-min running, and a 0, 1, 6, 24, 48, and 72 h post-exercise, and enzymes activity (CK, LDH, PFK, PK, SDH, and MDH) and substrates contents (glycogen and pyruvate) were measured biochemically. The time course of the enzyme activities showed two distinct patterns: CK, LDH, SDH, and MDH showed two peaks, at 0 and 24 h post-exercise, while PFK and PK showed one peak at 0 h post-exercise. The activities of glycolytic enzymes and CK in EDL and oxidative enzymes in SOL showed marked changes after exercise. The glycogen level was lowest at 0 h post-exercise in both muscles and recovered to resting level by 24 h post-exercise. Pyruvate increased with running and showed the highest value at 1 h post-exercise. Increased oxidative capacity of skeletal muscle in response to the acute endurance exercise dropped gradually to the resting level by 48 h post-exercise. An endurance exercise may induce a flexible adaptation on the oxidative capacity within skeletal muscle. We conclude that the respective time course of the enzyme activities must be considered when discussing metabolic changes that occur with acute endurance exercise.     

The effect of anabolic hormone 19-nortestosterone propionate on the metabolism of striated muscle during experimental ischaemia

Summary The effect of the anabolic hormone 19-nortestosterone propionate (Superanabolon Spofa) on the metabolism of chronically ischaemic striated muscle (anterior tibial m.) was studied in a described model in the rat.Metabolic changes were estimated in terms of the activities of a number of enzymes in muscle fibres. Enzyme activities (AcP, ATPase, CE, LDH, MDH) were determined both biochemically and histochemically excepting SDH, which was determined only by the histochemical way. Morphological changes were investigated by routine histology.Administration of 19-nortestosterone propionate prevented enzymatic changes which are typical for chronic ischaemia, primarily the decrease in the activities of dehydrogenases of Krebs' cycle tricarboxylic acides (MDH, SDH). In addition, the ratio of red to white muscle fibres increased. Administration of anabolic hormone has a similar favourable action on ischaemic muscle as training, studied previously.     

Neuroprotective effects of tramadol on cerebral injuries caused by hind limb ischaemia/reperfusion in rats

Skeletal muscle ischaemia–reperfusion-induced acute remote injury is mediated by activated neutrophils and formation of free radicals. Several investigators have demonstrated that the opioid pathway is involved in tissue preservation during hypoxia or ischaemia. Tramadol hydrochloride is an effective analgesic used for severe acute and chronic pain conditions. The present study was designed to investigate the potential protective effects of tramadol hydrochloride on cerebral oxidative stress and damage as well as lipid peroxidation, brain oedema and histological changes induced by hind limb ischaemia and reperfusion injury in rats. Thirty-six male Wistar rats were randomly allocated into two experimental groups: ischaemia–reperfusion (group I) and ischaemia–reperfusion + tramadol hydrochloride (group II). Hind limb ischaemia was induced by clamping the femoral artery. After 2-h ischaemia, the clamp from the femoral vessels was removed and the animal underwent 24-h reperfusion. Tramadol hydrochloride was given intravenously at a dose of 20 mg/kg, immediately before reperfusion. After reperfusion, animals were euthanized and the cerebral structure, lipid peroxidation and brain oedema in the cerebral tissue were assessed. Histopathological assessment of cerebral injury was split into four grades. The extent of lipid peroxidation was measured by estimating the amount of malondialdehyde. Brain oedema was calculated as the percentage water content of the brain. Brain oxidative stress and damage were significantly attenuated by treatment with tramadol hydrochloride. Compared with the ischaemia–reperfusion group, histological changes in brain tissues (p?p?P?相似文献   

Ischaemia-reperfusion injury of rat ovary and the effects of vitamin C,mannitol and verapamil

BACKGROUND: In this prospective controlled study, the aim was to examine the effects of vitamin C, mannitol and verapamil on adnexial ischaemia-reperfusion injury in the rat ovary. METHODS: Thirty-six female Wistar rats were used. In the controls (group 1), only laparotomy was performed. In group 2, ovarian ischaemia was produced and the bilateral ovaries were surgically removed 4 h later. In group 3, an ischaemic period of 4 h was followed by reperfusion for 1 h; the bilateral ovaries were then removed. In groups 4, 5 and 6, after 4 h of ischaemia, either vitamin C, mannitol or verapamil respectively was infused before reperfusion; after 1 h of reperfusion the ovaries were removed. Thiobarbituric acid reactive substance (TBARS) levels were measured in all ovary tissues. RESULTS: TBARS levels of the reperfusion group were significantly higher than those of groups treated with vitamin C or mannitol (P = 0.013 and P = 0.045 respectively), but not of the verapamil group. CONCLUSIONS: Vitamin C and mannitol were found to be effective in reducing ischaemia-reperfusion injury of the ovary during its early stages, but verapamil was ineffective.     

Origin and significance of small muscle fibres in neuromuscular disease

Summary Small muscle fibres, defined as those of less than 40 µm diameter in the male and 30 m in the female were encountered in muscle biopsies of patients with spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), polymyositis (PM) and myopathy/dystrophy. Excessive reactivity with NADH-TR in small fibres did not discriminate between neurogenic and myopathic disorders. Quantification of perifascicular atrophic fibres, the number of nuclei in atrophic fibres, or the presence of isolated or grouped small fibres without histochemical kinship to their surrounding fibres did not aid recognition of the disease process in the groups studied. Small fibres which reacted strongly both with NADH-TR and ATPase at pH 9.4 (Type 3 fibres) constituted 38% of small fibres in the biopsies of SMA; 25% in ALS; but only 1% and 2.7% in PM and myopathy/dystrophy respectively. Thus, the presence of small Type 3 fibres in muscle biopsies may be a useful marker for neurogenic disorders in adults.     

The effect of a synthetic hexadentate iron chelator (CP130) and desferrioxamine on rabbit kidneys exposed to cold and warm ischaemia

The effect of CP130 (a synthetic hexadentate pyridinone iron chelator) on the formation of two markers of lipid peroxidation (TBA-reactive material and Schiff's bases) in rabbit kidneys following a 72 h period of cold (0–4°C) ischaemia was investigated by either adding CP130 to the flush/storage solution (hypertonic citrate solution) or by administering the agent intravenously 15 min before removal of the organs. In both cases, CP130 blocked the adverse rises in lipid peroxidation caused by ischaemia and subsequent reoxygenation of the homogenatesin vitro. Both CP130 and desferrioxamine (DFX) (administered intravenously 15 min before ischaemia and 5 min before reperfusion) were also found to significantly reduce post-ischaemic rates ofin vitro lipid peroxidation in kidneys rendered warm ischaemic for 90 min followed by reperfusion for 5 or 60 minin situ. Kidneys exposed to warm ischaemia and reperfusion developed interstitial and intracellular oedema, congestion and haemorrhage. DFX administration had little effect on the histological outcome, whereas CP130 significantly reduced interstitial oedema (at 6 min reperfusion compared to the DFX-treated group), intracellular oedema (at 60 min reperfusion compared to the DFX-treated group) and congestion (at 5 min reperfusion compared with a control group not given any agent). It is concluded that while CP130 and DFX exhibited similar antioxidant properties, CP130 provided better protection from ischaemia/reperfusion injury at the histological level. Synthetic iron chelators may therefore be of benefit in clinical organ transplantation by protecting against tissue damage caused by prolonged ischaemia.     

The effect of strength training on estimates of mitochondrial density and distribution throughout muscle fibres

The purpose of this study was to investigate the effect of strength training (12 weeks, 3 days/week, four lower-body exercises) of young individuals (mean age 23.6 years) on estimates of mitochondrial distribution throughout muscle fibres. A control group (mean age 21.7 years) was followed simultaneously. Skeletal muscle biopsy samples were obtained from the vastus lateralis, pre- and post-training. The regional distribution of subsarcolemmal and intermyofibrillar mitochondrial populations was determined using quantitative histochemical staining of succinate dehydrogenase (SDH) in type I and II muscle fibres. Strength training resulted in significant increases of 26% and 28% in the cross-sectional area of type I and II fibres, respectively (P?P?相似文献   

Cytochrome c oxidase and cardiolipin alterations in response to skeletal muscle ischaemia and reperfusion

The effect of 2 and 4 h of tourniquet ischaemia followed by 1 h of reperfusion on the major mitochondrial phospholipids and on the cytochrome c oxidase kinetic parameters has been investigated in rat skeletal muscle. There was no change either in the mitochondrial phospholipid content or in the Vmax and the Km of the enzyme after 2 h of ischaemia with and without subsequent reperfusion. Four hours of ischaemia had no effect on the lecithin and the cephalin content, while the cardiolipin content decreased as well as the Vmax of the enzyme (P less than 0.05). Tissue reperfusion caused a dramatic decrease in both cardiolipin (55% of the control, P less than 0.001) and Vmax (38% of the control, P less than 0.001). The corresponding reduction in lecithin and cephalin contents was 12% and 14% respectively (P less than 0.05). The Km remained unchanged at all conditions. These findings suggest that mitochondrial dysfunction in response to ischaemia and reperfusion could be a consequence of the reperfusion itself following severe ischaemia. The results are discussed in terms of cardiolipin peroxidation and cytochrome oxidase as a functional parameter.     

Small accumulation of inosine monophosphate (IMP) despite high lactate levels in latissimus dorsi during transplantation

The effects of prolonged ischaemia and subsequent reperfusion during and after reconstructive microsurgery on energy metabolism were studied. Repeated skeletal muscle biopsies were taken and analysed for high energy phosphates and their degradation products by high performance liquid chromatography and for lactate by a fluorometric procedure. Moderate changes in adenine nucleotides occurred during the first 4 h of ischaemia. After 6 h of ischaemia, when the creatine phosphate store was almost depleted and the lactate level had increased to 111 mmol kg-1 dry muscle, ATP content decreased and inosine monophosphate started to accumulate. The inosine monophosphate accumulation was however small, in spite of a high lactate level, which suggests that the increase in H+ associated with lactate formation is not important for the activation of AMP-deaminase during the present conditions. In spite of the accelerating metabolic deterioration during the later period of ischaemia, the reperfusion of the muscle resulted in a rapid normalization of all the studied metabolites, thereby indicating a rapid restoration of the muscle energy stores.     

醒脑静注射液对全脑缺血再灌注大鼠血脑屏障ZO-1表达的影响

目的:探讨醒脑静(XNJ)注射液对大鼠全脑缺血再灌注后血脑屏障通透性及紧密连接蛋白1(ZO-1)表达的影响。方法:采用改良Pulsinelli四血管闭塞法建立大鼠全脑缺血再灌注模型。将雄性Wistar大鼠随机分为4组,即假手术组、全脑缺血再灌注模型组、溶剂对照组和XNJ组。每组均在缺血再灌注后24 h、48 h和72 h处理。用干湿重法测定脑组织中水含量,分光光度计法检测脑组织伊文思蓝(EB)含量,Western blot检测大脑皮层的ZO-1蛋白含量。结果:缺血再灌注后24 h,模型组、溶剂对照组和XNJ组的脑组织含水量均显著高于假手术组(P0.05),但在缺血再灌注后48 h和72 h,模型组和溶剂对照组脑组织含水量显著高于XNJ组和假手术组(P0.05)。缺血再灌注后24 h,模型组、溶剂对照组和XNJ组大鼠脑组织内EB含量均高于假手术组(P0.05),缺血再灌注后48 h和72 h,假手术组和XNJ组的EB含量显著低于模型组和溶剂对照组(P0.05)。缺血再灌注后24h,模型组、溶剂对照组和XNJ组大鼠脑皮层中的ZO-1蛋白表达水平显著低于假手术组(P0.05),同样缺血再灌注后48 h和72 h,假手术组和XNJ组皮层中ZO-1蛋白含量显著高于模型组和溶剂对照组(P0.05)。结论:在缺血再灌注后的48 h和72 h,醒脑静注射液对血脑屏障具有保护作用,可能与醒脑静注射液上调ZO-1蛋白的表达有关。     

双侧颈总动脉缺血再灌注后大脑皮质一氧化氮合酶和生长抑素的表达

目的:探讨脑缺血再灌注后大脑皮质一氧化氮合酶(NOS)和生长抑素(SS)的基因表达及其意义。方法:取Wistar大鼠,缺血再灌注分6、24和72 h组。测试大脑皮质一氧化氮合酶和生长抑素蛋白表达水平。结果:NOS缺血再灌注6、24 h组和对照组相比阳性神经元数明显升高;缺血再灌注72 h与6、24 h组相比阳性神经元数明显下降;SS缺血再灌注6、24、72 h组与对照组相比阳性神经元数明显下降;缺血再灌注72 h组比缺血再灌注6 h组下降更低。结论:NOS和SS通过多种途径参与了脑缺血再灌注后细胞损伤的发生。