Biomarkers in peripheral blood associated with vascular injury in Sprague-Dawley rats treated with the phosphodiesterase IV inhibitors SCH 351591 or SCH 534385

Drug-associated vascular injury can be caused by phosphodiesterase (PDE) IV inhibitors and drugs from several other classes. The pathogenesis is poorly understood, but it appears to include vascular and innate immunological components. This research was undertaken to identify changes in peripheral blood associated with vascular injury caused by PDE IV inhibitors. We evaluated twelve proteins, serum nitrite, and leukocyte populations in peripheral blood of rats treated with experimental PDE IV inhibitors. We found that these compounds produced histological microvascular injury in a dose- and time-dependent manner. Measurement of these serum proteins showed changes in eight of the twelve examined. Changes were seen in the levels of: tissue inhibitor of metalloproteinase-1, alpha1-acid glycoprotein, GRO/CINC-1, vascular endothelial growth factor, C-reactive protein, haptoglobin, thrombomodulin, and interleukin-6. No changes were seen in levels of tumor necrosis factor-alpha, hepatocyte growth factor, nerve growth factor, and granulocyte-monocyte colony stimulating factor. Serum levels of nitrite were also increased. Circulating granulocyte numbers were increased, and lymphocyte numbers were decreased. The changes in these parameters showed both a dose- and time-dependent association with histopathologic changes. These biomarkers could provide an additional tool for the nonclinical and clinical evaluation of investigational compounds.     

Histopathology of vascular injury in Sprague-Dawley rats treated with phosphodiesterase IV inhibitor SCH 351591 or SCH 534385

Histopathological and immunohistochemical studies were conducted to characterize vascular injuries in rats treated with phosphodiesterase (PDE) IV inhibitors SCH 351591 or SCH 534385. Sprague-Dawley rats were administered PDE IV inhibitors by gavage at a range of doses and times. The two PDE IV inhibitors induced comparable levels of vascular injury, primarily in the mesentery and to a lesser extent in the pancreas, kidney, liver, small intestine, and stomach. Mesenteric vascular changes occurred as early as one hour, progressively developed over twenty-four to forty-eight hours, peaked at seventy-two hours, and gradually subsided from seven to nine days. The typical morphology of the vascular toxicity consisted of hemorrhage and necrosis of arterioles and arteries, microvascular injury, fibrin deposition, and perivascular inflammation of a variety of blood vessels. The incidence and severity of mesenteric vascular injury increased in a time- and dose-dependent manner in SCH 351591- or SCH 534385-treated rats. Mesenteric vascular injury was frequently associated with activation of mast cells (MC), endothelial cells (EC), and macrophages (M?). Immunohistochemical studies showed increases in CD63 immunoreactivity of mesenteric MC and in nitrotyrosine immunoreactivity of mesenteric EC and M?. The present study also provides a morphological and cellular basis for evaluating candidate biomarkers of drug-induced vascular injury.     

Sodium reabsorption in the papillary collecting duct of rats

Using the shrinking droplet method and simultaneous perfusion of the peritubular capillaries the isotonic reabsorption of Ringer's solution from the papillary collecting ducts was measured. Under control conditions the volume reabsorption from the papillary collecting ducts wasJ _v±SE=2.6±0.1 · 10^–5 cm³ · cm^–2 · s^–1. In rats which were on low Na⁺ diet,J _v increased to 127%, and in adrenalectomized animals it decreased to 34% of the control value. Three hours after application of aldosterone in the adrenalectomized animalsJ _v was partially restored to 63% of control rats. Amiloride 10^–4 M, added to the luminal perfusate, produced a strong inhibition ofJ _v (to 32% of control). Acetazolamide, 10^–4 M, added to both perfusates, reducedJ _v very strongly (to 40% of control), while omission of bicarbonate reduced it only to 77% of control. Acetazolamide, added to bicarbonate-free perfusates, did not result in a significant further reduction ofJ _v. The data indicate that the Na⁺ reabsorption from the papillary collecting duct is controlled by mineralocorticoids. Furthermore, they suggest the existence of two transport mechanisms in the luminal cell membrane: 1. An amiloride-sensitive entry step and 2. an entry step via a Na⁺–H⁺-countertransport mechanism, the latter being less important.     

Bicarbonate reabsorption in the papillary collecting duct of rats

Using the technique of capillary perfusion and simultaneous luminal stop flow microperfusion the reabsorption of bicarbonate and glycodiazine from the papillary collecting duct was evaluated. Starting with equal H¹⁴CO ₃ ^– and³H-glycodiazine concentrations in the luminal and peritubular perfusates, the decrease in the luminal concentration at 10 and 45 s contact time was measured.In control rats with 25 mmol/l HCO ₃ ^– in the perfusates the rate of HCO ₃ ^– reabsorption calculated from the 10 s values was 0.34 nmol cm^–2s^–1. In acute metabolic acidosis, the rate of bicarbonate reabsorption was 2,3 times higher. In metabolic alkalosis, the rate of bicarbonate absorption dropped to 13% of the control values. Also the 45 s values of acidotic and alkalotic animals differed significantly from each other. With 25 mmol/l glycodiazine in both perfusates the rate of biffer reabsorption as calculated from the 10 s values was 0.76 nmol cm^–2s^–1 in control rats and did not deviate significantly from this value in acidotic and alkalotic animals.In control rats the bicarbonate reabsorption in % was the same, no matter whether both luminal and capillary perfusate contained 25 mmol/l bicarbonate or 10 mmol/l. In acidotic rats the rate of HCO ₃ ^– reabsorption did not change significantly if all Na⁺ in the perfusates was replaced by choline (0.88 versus 0.79 nmol cm^–2s^–1 at 25 mmol/l HCO ₃ ^– ). When in acidotic rats 0.1 mmol/l acetazolamide or 1 mmol/l SITS (4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid) was added to both perfusates the rate of HCO ₃ ^– reabsorption dropped by 75 and 58%, respectively. A potassium deficient diet for one week and DOCA administration had no influence on the bicarbonate reabsorption of rats which were on standard diet.The data indicate that (1) the buffer reabsorption from the papillary collecting duct is rather due to H⁺ ion secretion than to buffer anion reabsorption. (2) The adaptation to metabolic acidosis and alkalosis is specific for bicarbonate and not seen with glycodiazine. (3) Within the concentration range tested the HCO ₃ ^– reabsorption rises linearly with the HCO ₃ ^t- concentration. (4) The HCO ₃ ^– reabsorption in the papillary collecting duct is Na⁺-independent, it can be inhibited by acetazolamide and SITS, but is not influenced by K⁺-deficient diet plus DOCA.     

Spontaneous occurrence of spastic paresis in Han-Wistar rats

The occurrence of spastic paresis and paralysis in rats of the Han: WIST strain is described. The results of this study indicate that this neural disorder starts with progressive development at the age of about 4–5 weeks independent of the sex. At this time the affected animals are significantly smaller than the normal ones. The disease has been found to be due to an autosomal recessive gene. Electromyographic studies showed spontaneous discharges of tonic firing motor units.     

Sorbitol metabolism in inner medullary collecting duct cells of diabetic rats

Intracellular accumulation of sorbitol, generated fromd-glucose via the aldose reductase pathway, is thought to play an important role in diabetic complications such as lens cataracts and neuropathy. In order to elucidate the effect of diabetes on the renal inner medulla, another sorbitol-rich tissue, male Wistar rats were treated with a single dose of streptozotocin (60 mg/kg body weight, i.p.). Six wecks later total inner medullary tissue (IM) or isolated inner medullary collecting duct (IMCD) cells were prepared. In diabetic IM tissue, sorbitol content was 1.8-fold higher than in control IM tissue (134±17 vs. 74±22 mol/g tissue protein). Sorbitol production in both normal and diabetic IMCD cells was strongly dependent on extracellulard-glucose concentration. In normal cells, for example, sorbitol production was 90±9 mol sorbitol/g protein x h at 45 mMd-glucose compared to 13±1 mol/g protein x h at 5 mM. At identicald-glucose concentrations sorbitol synthesis in diabetic IMCD cells was, however, always significantly higher than in control cells (122% of control at 15 mM and 126% of control at 45 mM). In addition, aldose reductase activity in diabetic IM was found to be augmented. The maximal velocity was 4.2 times higher (97±22 U/g protein vs. 23±7 U/g protein) while theK _m of the enzyme remained unchanged. Membrane permeability for sorbitol or the response to changes in extracellular osmolarity was not significantly different in diabetic IMCD cells and normal cells with correspondingly high intracellular sorbitol concentrations. Similarly the kinetic parameters ofd-glucose uptake were not altered by streptozotocin treatment. These results suggest that increased medullary sorbitol content in diabetic rats is a result of increased sorbitol synthesis due to a higher extracellulard-glucose concentration and augmented aldose reductase activity in face of an unaltered sorbitol permeability of the plasma membrane.     

SD大鼠脊髓损伤后微环境的模拟实验

BACKGROUND: We built Sprague-Dawley rat models with mild, moderate, and severe spinal cord injuries to accord with the spinal cord injury types for basic empirical study, and consequently to further understand the microenvironmental change in Sprague-Dawley rats with spinal cord injury, and to provide help for clinical treatment. OBJECTIVE: To observe the changes in nerve function, pathological manifestation and motor sensory evoked potential in Allen’s models and Sprague-Dawley rats with complete spinal cord transection at different time points after spinal cord injury by simulating the microenviroment in Sprague-Dawley rats. METHODS: A total of 125 healthy adult female Sprague-Dawley rats were selected and randomly divided into group sham operation group, 100 gcf hit potential group (20 g×5 cm), 200 gcf hit potential (20 g×10 cm), 300 gcf hit potential group (20 g×15 cm), and spinal cord complete transection group with 25 rats in each group. At 1, 5, 7, 14 and 28 days after model establishment, the degree of spinal cord injury was identified by the BBB scores of motion function, motor evoked potential, and pathological section. RESULTS AND CONCLUSION: (1) Totally 24 Sprague-Dawley rats died in the experiment. The death rate and the rate of complications were highest in the spinal cord complete transection group. The BBB score of each group was decreased. The BBB scores in every group increased as time went on. There were significant differences between each surgery group and the sham operation group at corresponding time points (P < 0.05).  No significant difference was found between the 300 gcf hit potential group and the spinal cord complete transection group at corresponding time points (P > 0.05). (2) In each surgery group, the infiltration of inflammatory cells and obvious swelling of neurons were visible at 1 day after injury. Neural cells reduced with time prolonged. At 28 days after injury, a large number of astrocytes proliferated, scar and spinal cord cavity formed. Above symptoms were worse in the 300 gcf hit potential group and spinal cord complete transection group than in the 100 gcf and 200 gcf hit potential groups. (3) Significant differences in amplitude and latency were detectable between each surgery group and the sham operation group (P < 0.05). No significant difference in amplitude and latency was detected between the 300 gcf hit potential group and the spinal cord complete transection group at corresponding time points (P > 0.05). Results confirmed that hit potential of 20 g×5 cm, 20 g×10 cm and 20 g×15 cm can simulate the microenvironment of Sprague-Dawley rats with mild, moderate and severe spinal cord injury. The rate of complication was lower in modified Allen’s model of different hit potentials than in models of spinal cord complete transection, and was more accorded with basic research.       

Neuronal degeneration in hippocampus and cerebellum of mutant spastic Han-Wistar rats

The neuropathology of the brain of mutant spastic Han-Wistar rats (Han-Wist SPA/SPA) was investigated using histological techniques. A surprising result was the detection of neuronal degeneration in the hippocampus and cerebellum of mutant spastic rat brains, whereas other regions, e.g. neocortex, isocortex, basal ganglia and thalamus, were overall normal. The CA3 sector in the septal third of the hippocampus including the cell band reaching into the hilus ('CA3c') showed a severe neuronal degeneration, whereas the granule cells of the dentate gyrus, several hilar neurons ('CA4') and the pyramidal cells in CA1 were found normal. In the cerebellum, a variable patchy degeneration of Purkinje cells was detected while the general layering was normal and granule cells and Golgi cells appeared preserved.     

SD大鼠股骨骨折合并脊髓损伤模型的构建

背景：骨折合并脊髓损伤的动物模型创伤大,造模后存活率较低,而改良Allen法和股骨开放截骨法制作动物模型时操作简单,不需要特殊器械,建模时间及出血较少,适用于骨折合并脊髓损伤动物模型的制作。 目的：建立一种既能成功维持长时间存活,并符合临床特征,又简便易行的实验动物模型。 方法：将48只SD雄性大鼠随机数字表法均分为单纯股骨骨折组和股骨骨折合并脊髓损伤组,通过双侧小切口开放截骨造成股骨中端横行骨折并植入内固定建立股骨骨折模型,改良Allen法自制打击装置造成大鼠T10段脊髓急性挫伤性损伤,两种方法融合制造股骨骨折合并脊髓损伤模型,观察大鼠制模成功后不同时间点大体情况及4周后骨折断端愈合情况。 结果与结论：建模后骨折合并脊髓损伤动物模型均成活,双下肢感觉及运动功能丧失,但可利用双上肢缓慢匍匐向前移动,前3 d进食少,活动少,夜间采用尾端悬吊后,骨折患肢未出现缺血坏死,到达第4周时,单纯股骨骨折组死亡1只,股骨骨折合并脊髓损伤组共死亡4只,成活率为83.33%,髓腔内固定未见脱出,两组骨折断端均有连续骨痂生成,从体积上来看,股骨骨折合并脊髓损伤组骨痂组织明显大于单纯股骨骨折组。证实将改良Allen法与小切口股骨外侧开放截骨法结合后,简单易行,可以成功制作股骨骨折合并脊髓损伤动物模型并成活至第4周。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

Structural and functional changes in epitheliocytes of collecting tubes in renal papilla of Brattleboro rats treated with vasopressin

The functional response of the kidney to desmopressin and morphological changes in epitheliocytes of collecting tubes were studied on homozygotic Brattleboro rats. Redistribution of β-glucuronidase fractions and increase in the number of osmiophilic granules reflecting increased production of vasopressin-dependent proteins and hyaluronate hydrolase exocytosis were typical structural correlates of the effect of vasopressin. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 101–105, January, 2007     

Urea reabsorption in the medullary collecting duct of protein-depleted young rats before and after urea infusion

The aims of the present study were to examine urea handling along the length of the medullary collecting duct (MCD) in protein-depleted young rats and to determine the effect of urea infusion on MCD function and urine concentrating ability. In 10 young rats on a low protein diet, urea reabsorption equivalent to 18.3% of the filtered load was observed along the MCD (4.5 mm) using the microcatheterization technique. Collecting duct urea reabsorption occurred almost entirely (16.6%) in the distal portion of the MCD (mid-zone to papillary tip, 2.8 mm). These results are in contrast to the lack of net urea reabsorption along the MCD in protein-replete adult rats [21]. After urea infusion which raised plasma urea level from 3.5 to 10.5 mmol/l in protein-depleted rats, urine non-urea solute concentration increased in the non-exposed right kidney from 827 to 1,199 mosm kg^–1 (P<0.001) but the increase was not significant in the experimental left kidney (590 to 619 mosm kg^–1). Thus exposure of the papilla interfered with urea-induced enhancement of urine concentrating ability. After urea infusion, fractional urea reabsorption in the distal portion of the MCD was similar to that before infusion (21.1%) of filtered load) but the absolute load of urea delivered to the MCD and reabsorbed along the duct was markedly increased (2.7-fold). In 6 rats with an increase in urine non-urea solute concentration in the experimental kidney after urea infusion, fluid reabsorption along the duct was significantly increased. The results indicate that in protein-depleted young rats (1) there is significant urea reabsorption in the distal portion of the medullary collecting duct, (2) urea infusion contributes to enhanced urine concentrating ability, in part, by increasing absolute urea reabsorption and also water reabsorption in the collecting duct.     

Antidiuretic hormone reduces the high PGE2 synthesis in papillary collecting duct of DI rats

PGE₂ synthesis was measured along the nephron of Brattleboro (DI) rats, lacking ADH, and control LE rats, using an enzyme immunossay. Experiments were performed in vitro, in the absence of exogenous arachidonic acid, using microdissected tubular segments. The effect of a chronic treatment by dDAVP was tested on three ADH sensitive tubular segments, medullary thick ascending limb (MTAL), medullary collecting tubule (OMCD) and papillary collecting duct (IMCD).No difference in PGE₂ synthesis was present between LE and DI in glomerulus and tubular segments up to OMCD. In both strains, values were low in the proximal tubule and the loop of Henle, and gradually increased along the collecting tubule. In IMCD, PGE₂ synthesis was much higher in DI (12.8±2.0 pg per 30 min per mm tubular length) than in LE (3.8±0.5, LE vs. DIp<0.001).In MTAL and OMCD, dDAVP treatment did not affect PGE₂ synthesis. In IMCD, dDAVP reduced PGE₂ synthesis to values (5.3±0.8 pg per 30 min per mm tubular length), which were not significantly different from those of LE. Neither oxytocin, which has been shown to be elevated in DI rats, nor furosemide, that reduced papillary osmolarity to values comparable to those of DI rats, were able to increase PGE₂ synthesis in IMCD of LE rats. The mechanism of the increase in PGE₂ synthesis in IMCD of DI rats, and of the inhibitory effect of dDAVP is yet unknown; it may participate to compensate for the lack of ADH in the Brattleboro rat.     

Immunoselection and culture of cortical collecting duct cells

Summary A straightforward method is described for isolating and culturing cells from the renal cortical collecting duct. This method uses monoclonal antibodies and solid phase immunoadsorption to select for the targeted cell population. The large number of cells obtained with this method facilitates biochemical studies and initiation of cell cultures. Monolayers grown on permeable membranes can be used for studying mechanisms of ion transport and cell differentiation as well as their hormonal regulation. This study was supported by grants DK 41841 and DK 39523 from the National Institutes of Health, Bethesda, MD, and by a Grant-in-Aid from the American Heart Association (89 985).     

Role of the medullary collecting duct in potassium conservation

A capacity for both net potassium absorption and net potassium secretion has been demonstrated in the inner medullary collecting duct. The quantitative importance, however, of the inner medullary collecting duct in the regulation of urinary potassium in potassium deficiency, however has not been established. To assess the contribution of this segment to potassium conservation, microcatherization studies were performed in male Sprague-Dawley rats maintained either on a control diet or on a potassium free diet for 72 h. In control animals approximately 15% of the filtered load of potassium was excreted. Analysis of tubule fluid along the inner medullary collecting duct failed to demonstrate evidence of net potassium movement. Administration of a potassium free diet resulted in a marked reduction in potassium excretion to 0.3% of the filtered load. In contrast to control the inner medullary collecting duct of experimental animals absorbed nearly 90% of the amount of potassium entering this segment, since fractional delivery to the terminal portion of the nephron was about 2%. These data indicate that the inner medullary collecting duct makes a significant contribution to maximal renal conservation of potassium, since previous studies have shown that only 5 to 10% of filtered potassium is present in the late distal tubule of surface nephrons in animals on a low potassium intake.     

Centroacinar and intercalated duct cells as potential precursors of pancreatic endocrine cells in rats treated with streptozotocin

The present study examined the possibility for regeneration of pancreatic endocrine cells from centroacinar (CA) and intercalated duct (ICD) cells in rat pancreas after 5 days of continuous streptozotocin (STZ) administration. Nine rats were divided into 3 experimental groups: 1) Control group, 2) Short term recovery group; three days after STZ administration (STZ 3), and 3) Long term recovery group; ten days post-STZ administration (STZ 10). The CA and ICD cells in the STZ 3 group had swollen cytoplasm, and sometimes contained a vesicle within the core. An insulin positive signal was detected in and around the CA and ICD cells. In the STZ 3 group, cytokeratin 20 signals were co-localized with insulin signals in both CA and ICD cells. Electron microscopically, endocrine cells and small pancreatic islets were in close contact with CA and ICD cells. Systemic biophysical serum data reflected these immunohistological results. The present results suggest that CA and ICD cells are involved in the regeneration of pancreatic B cells in rats following a lesion produced by five consecutive days of STZ administration.     

DNA sequence analysis of hprt mutations in lymphocytes from Sprague-Dawley rats treated with 7,12-dimethylbenz[a]anthracene

Treatment of female Sprague-Dawley rats with the potent mammary gland carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) results in the formation of DNA adducts with dG and dA and in the induction of 6-thioguanine-resistant (TG′) lymphocyte mutants. In this study, we have examined the types of mutations induced in TG′ lymphocytes from DMBA-treated rats. DNA from 263 TG′ lymphocyte clones was screened for mutations in exons 2, 3, and 8 of the hprt gene by polymerase chain reaction (PCR) amplification of the exons followed by heteroduplex analysis using denaturing gradient-gel electrophoresis. Twenty-five of the clones produced heteroduplexes in exon 2, 35 produced heteroduplexes in exon 3, and 36 produced heteroduplexes in exon 8. Direct sequence analysis of the heteroduplexes revealed 96 mutations, and at least 74 of these mutations were produced independently. Eighty-five of the total mutations were simple base pair (bp) substitutions, with A → T and G → T transversions being the predominant types. Seven mutations were deletions, three were complex bp substitutions, and one was an insertion. The results suggest that the types of mutations produced by DMBA in rat lymphocytes are specific to the DNA adducts produced by this compound. © 1996 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Role of [Ca2+]i in lethal oxidative injury in rat cultured inner medullary collecting duct cells

Reactive oxygen metabolites have been implicated in the pathogenesis of toxic, ischaemic and immunologically mediated renal injury. An increase in the cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) has been proposed as a mechanism of oxidative stress-induced cell injury. We used a fluorescence spectrometer and a fluorescence probe to measure the [Ca²⁺]_i and viability of rat primary cultured inner medullary collecting duct (IMCD) cells during oxidative stress induced by 5 mM tert-butyl hydroperoxide (TBHP). Initially, this oxidative stress evoked a small increase in [Ca²⁺]_i which was followed by a slower sustained increase from the resting level of 170.8±38.8 nM to 1490.5±301.7 nM after 60 min, and this preceded the loss of plasma membrane integrity, measured by the propidium iodide fluorescence method. The elimination of extracellular Ca²⁺ from the culture medium prevented the TBHP-induced [Ca²⁺]_i increase and improved cell viability. Restoration of extracellular Ca²⁺ resulted in an immediate and large increase in [Ca²⁺]_i and extensive cell death. Verapamil, a Ca²⁺ channel blocker, inhibited the [Ca⁺]_i increase and afforded significant protection against cellular injury following exposure to TBHPinduced oxidative stress. Extracellular acidosis also prevented the increase in [Ca²⁺]_i and cell death caused by this oxidative stress. These results are consistent with the hypothesis that oxidative stress-induced IMCD cellular injury may be the result of increased [Ca²⁺]_i caused, in part, by activation of voltage-dependent Ca²⁺ channels.     

肠系膜淋巴管结扎对大鼠急性肺损伤的影响

目的：探讨结扎肠系膜淋巴管对失血-脂多糖（LPS）致大鼠急性肺损伤（ALI）的拮抗作用。方法：雄性Wistar大鼠45只，均分为结扎组、未结扎组、假手术组，以失血、LPS复制二次打击模型，结扎组行肠系膜淋巴管结扎术致肠淋巴液断流。在手术创伤后24 h，所有大鼠颈总动脉放血，进行血气分析；从左肺收集支气管肺泡灌洗液（BALF），观察WBC、NO及其合酶、SOD、MDA以及肺泡通透性指数等指标的水平；右肺制备10%组织匀浆，检测MPO、ATPase活性等指标；观察右肺后叶超微结构。结果：二次打击后，未结扎组动脉血PaCO2、BALF中细胞总数及PMN、NO2-/NO3-、NOS、MDA含量以及肺匀浆MPO活性、肺通透性指数均显著高于假手术组，动脉血pH、PaO2、BALF中SOD、肺匀浆ATPase活性显著低于假手术组（P<0.01，P<0.05）；结扎组大鼠BALF中细胞总数及PMN、MDA、NO2-/NO3-含量、肺通透性指数均显著高于假手术组，BALF中SOD活性显著低于假手术组（P<0.01，P<0.05）。但结扎组大鼠动脉血pH、PaO2、肺匀浆ATPase活性显著高于未结扎组，动脉血PaCO2、BALF中细胞总数及PMN、NO2-/NO3-、NOS、MDA含量、肺通透性指数及肺匀浆MPO显著低于未结扎组（P<0.01，P<0.05）；且肺血管内皮细胞损伤程度较未结扎组轻微。结论：肠系膜淋巴管结扎可减轻失血-LPS致大鼠的急性肺损伤。提示二次打击的肠系膜淋巴液在大鼠急性肺损伤的发病过程中发挥着重要作用。