Poly(Adp-ribose) synthetase inhibition prevents lipopolysaccharide-induced peroxynitrite mediated damage in diaphragm.

Although the precise mechanism by which sepsis causes impairment of respiratory muscle contractility has not been fully elucidated, oxygen-derived free radicals are thought to play an important role. In our experimental study, the effects of poly(ADP-ribose) synthetase (PARS) inhibition on the diaphragmatic Ca(2+)-ATPase, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) levels and additionally histopathology of the diaphragm in lipopolysaccharide (LPS)-induced endotoxemia are investigated.Thirty-two male Wistar rats, weighing between 180-200 g were randomly divided into four groups. The first group (control; n=8) received saline solution and the second (LPS group; n=8) 10 mgkg(-1) LPS i.p. 3-Aminobenzamide (3-AB) as a PARS inhibitor; was given to the third group (C+3-AB, n=8) 20 min before administration of saline solution while the fourth group (LPS+3-AB, n=8) received 3-AB 20 min before LPS injection. Six hours later, under ketamin/xylasine anesthesia diapraghmatic specimens were obtained and the rats were decapitated. Diaphragmatic specimens were divided into four parts, three for biochemical analyses and one for histopathologic assessment. In the LPS group, tissue Ca(2+)-ATPase levels were found to be decreased and tissue MDA and 3-NT levels were found to be increased (P<0.05). In the LPS+3-AB group, 3-AB pretreatment inhibited the increase in MDA and 3-NT levels and Ca(2+)-ATPase activity remained similar to those in the control group (P<0.05). Histopathologic examination of diaphragm showed edema between muscle fibers only in LPS group.PARS inhibition with 3-AB prevented not only lipid peroxidation but also the decrease of Ca(2+)-ATPase activity in endotoxemia. These results highlights the importance of nitric oxide (NO)-peroxynitrite (ONOO(-))-PARS pathway in preventing free radical mediated injury. PARS inhibitors should further be investigated as a new thearapetic alternative in sepsis treatment.     

缺血后处理减轻大鼠肢体缺血再灌注后肺损伤的实验研究

摘要： 目的 观察缺血后处理 （I-postC） 对大鼠肢体缺血再灌注 （LIR） 后肺损伤的影响, 探讨缺血后处理的器官保护作用及可能机制。方法 Wistar 大鼠 24 只随机分为 3 组 （n=8）, 对照组 （Control 组）、 缺血再灌注组 （IR 组） 和缺血后处理组 （I-postC 组）。结扎大鼠双后肢根部以阻断血流 4 h, 后再恢复血流灌注 4 h, 制作大鼠 LIR 动物模型。 Control 组橡皮带松弛环绕双后肢不阻断血流, I-postC 组在血流再灌注前, 行重复 3 次的缺血 5 min-再灌注 5 min,再恢复 4 h 的血流再灌注。留取血液及肺组织标本, 测定各组动物动脉血气指标氧分压[p （O2 ） ]和二氧化碳分压 [p （CO2 ） ], 检测血浆及肺组织的丙二醛 （MDA） 含量及黄嘌呤氧化酶 （XOD） 和超氧化物歧化酶 （SOD） 水平, 光镜及电镜下观察肺组织的病理形态学改变。结果 LIR 后 p （O2 ） 和 p （CO2 ） 明显降低, 血浆和肺组织中 SOD 活性明显降低,而 XOD、 MDA 明显增加 （P < 0.05）; 镜下可见肺间质内血管扩张充血, 中性粒细胞浸润, 血管周围间隙增大, 肺泡间隔增宽, 肺泡腔内有渗出液等损伤表现。与 IR 组比较, I-postC 组 p （O2 ） 和 p （CO2 ） 明显增加, 血浆及肺组织 SOD 活性升高; 而 XOD、 MDA 水平降低 （P < 0.05）; 镜下观察肺组织只可见轻度病理改变。结论 I-postC 可通过抑制脂质过氧化反应减轻大鼠 LIR 后肺损伤的程度。     

Caffeic acid phenethyl ester (CAPE) protects rat skeletal muscle against ischemia-reperfusion-induced oxidative stress

Oxygen-derived free radicals have been implicated in the pathogenesis of skeletal muscle injury after ischemia-reperfusion. Caffeic acid phenethyl ester, an active component of propolis extract, exhibits antioxidant properties. The aim of this study was to assess the effects of caffeic acid phenethyl ester (CAPE) and alpha-tocopherol (vit E) on ischemia/reperfusion (I/R) injury in a rat hind limb ischemia/reperfusion model. For this purpose, ischemia was induced in anesthetized rats by unilateral (right) femoral artery clipping for 2 h followed by 2 h of reperfusion. Four groups were studied: sham, I/R, I/R+CAPE and I/R+vit E. Drugs were administered intraperitoneally after 1 h of ischemia and I/R rats received saline vehicle. After 2 h of reperfusion, venous blood was sampled and the right gastrocnemius muscle was harvested. Plasma and tissue were assayed for malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) metabolites. Tissue was also assayed for catalase (CAT) activity. Both tissue and plasma NO levels, MDA levels, SOD activities was significantly increased in I/R groups compared to control groups. The two treated groups showed decreased MDA and NO in both muscle and plasma compared to the I/R group. No differences were noted in muscle tissue SOD in three I/R groups, but SOD activity were increased in the plasma of I/R+CAPE and I/R+vit E groups compared with I/R group. Whereas tissue CAT activity was not changed among groups. Our results indicate that CAPE has antioxidant properties similar to those of vit E in this model and may attenuate the harmful effects of hind limb I/R in skeletal muscle.     

The role of poly(ADP-ribose) synthetase inhibition in preventing endotoxemia-induced intestinal epithelial apoptosis.

In this lipopolysaccharide (LPS)-induced endotoxemia model, the effects of 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, on ileal apoptosis were evaluated by light microscopy and M30 cell death staining. Moreover, the relationship between Bcl-2, iNOS expression, and serum nitrate (NO(3)(-)) levels were investigated. Thirty-two male Wistar rats, weighing 180-220g were randomly divided into four groups. The group I (control; n=8) received saline and group II (sepsis; n=8) received 10 mg kg(-1) LPS intraperitoneally. 3-AB was given to the group IV (S+3-AB; n=8) 20 min before giving LPS and to the group III (C+3-AB; n=8) 20 min before giving saline. Six hours later, blood and ileum samples were taken. Endotoxemic group exhibited significant apoptosis in intestinal epithelial cells and the immunohistochemical examination with M30 was demonstrated that the 3-AB reduced the LPS-induced intestinal apoptosis. Serum NO(3)(-) level was increased in endotoxemic group, whereas the elevation of NO(3)(-) level was prevented in LPS+3-AB group (P<0.05). The increased iNOS expression observed in the LPS group was also prevented by 3-AB. Compared with the endotoxemic group, ileal epithelial columnar cells from LPS+3-AB group had a dense Bcl-2 staining which was almost identical with control. In conclusion, 3-AB decreases LPS-induced apoptosis in ileum by preventing LPS-induced depletion of Bcl-2 and blocking iNOS gene. Modification of Bcl-2 expression by PARS inhibitors should further be investigated as a new therapeutic alternatives in septic states.     

参附注射液预处理对大鼠肝缺血再灌注肠黏膜屏障的保护作用

目的 探讨参附注射液（SF）对大鼠肝缺血再灌注损伤肠黏膜的保护作用。方法选用健康雄性SD大鼠90只,阻断第一肝门建立肝缺血再灌注模型,随机分为假手术组（SO组）、0．9％氯化钠注射液（NS）对照组（IR＋Ns组）和参附注射液治疗组（IR＋sF组）,SO组和IR＋NS组于再灌注前用与SF注射液等量之NS注射预处理,IR＋sF组则用SF灌注前做预处理,每组30只。建立肝缺血再灌注模型后再分为6h和12h两个时相点组,每组15只。检测血浆内毒素含量、ALT、丙二醛（MDA）和统计肠系膜淋巴结细菌移位率,并用光镜观察肠组织的病理变化。结果细菌移位率、内毒素、ALT和MDA水平IR＋sF组均较1R＋Ns组低。结论参附注射液对肝缺血再灌注后的肠黏膜屏障损伤有保护作用。     

支气管肺泡灌洗后兔肺组织的病理观察

目的观察支气管肺泡灌洗后兔肺组织病理变化。方法将实验用新西兰兔31只予以气管插管并分为生理盐水10ml(A组,n=11)、亚胺培南(50mg/10ml)(B组,n=8)和氟康唑(800μg/10ml)(C组,n=12)3组。灌洗2h后处死动物,采用常规石蜡组织切片和HE染色法对兔肺组织进行病理观察。结果肺细支气管腔和部分肺泡腔内可见淡红色液体,并由此导致局限性肺气肿和/或肺不张。肺细支气管管腔内和管壁积有散在的中性粒细胞;支气管黏膜上皮坏死、剥脱。3组上述病变组间无明显差异。结论与生理盐水灌洗比较,亚胺培南或氟康唑局部肺泡灌洗并未增加局部病理损伤。     

牛磺酸对大鼠肢体缺血再灌注所致肺损伤过程中内源性NO的影响

目的　在大鼠肢体缺血再灌注 (LIR)损伤模型上 ,研究内源性一氧化氮 (NO)在IR后肺损伤发生中的作用 ,观察牛磺酸对NO的影响 ,探讨牛磺酸防治LIR后肺损伤的机制。方法　Wistar大鼠随机分为 3组 ,即 :对照组 (control)、缺血再灌注组 (IR)、牛磺酸 +缺血再灌注组 (Tau +IR) ,分别测定动脉血氧分压 (PaO2 )和二氧化碳分压 (PaCO2 ) ,肺系数 (LI)和肺通透指数 (LPI) ,肺组织一氧化氮合酶 (NOS)活性、牛磺酸 (taurine)含量及血浆、肺组织丙二醛 (MDA)、NO和内皮素 (ET)含量 ,并用免疫组织化学方法观察各组动物肺组织NOS表达的变化。结果　牛磺酸可明显改善LIR后肺呼吸功能 ,减轻肺水肿的发生 ;降低血浆和肺组织ET的含量 ,提高血浆及肺组织NO含量 ,促进NOS的表达。结论　外源性牛磺酸可减轻LIR后肺损伤的发生 ,其机制之一与增加内源性NO含量和减少ET水平有关。     

奥扎格雷对大鼠肢体缺血再灌注所致肺损伤的保护作用

目的：探讨奥扎格雷钠(Ozagrel sodium)对大鼠肢体缺血再灌注后肺损伤的影响。方法：将60只雄性SD大鼠随机分成正常对照组、缺血再灌注组和奥扎格雷组,建立大鼠肢体缺血再灌注损伤模型。利用光镜和电镜观察肺组织形态学改变和超微结构改变,利用竞争放射免疫分析法测定血浆血栓素A2（TXA2)代谢产物血栓烷素B2(TXB2)和前列环素(PGI2)代谢产物6-酮-前列腺素F1a(6-Keto-PGF1a),比色法测定肺组织中丙二醛（MDA）、超氧化物歧化酶(SOD)、黄嘌呤氧化酶（XOD）,双抗体夹心ABC-ELISA法测定肺组织中白细胞介素(IL)-8、肿瘤坏死因子(TNF )-α,并进行比较。结果：与缺血再灌注组相比,奥扎格雷组肺血管扩张、炎性细胞聚集、组织水肿等均减轻,线粒体水肿、空泡变性,内膜下基底膜水肿、内皮细胞肿胀等情况明显减轻;血浆TXB2和6-keto-PGFla含量显著降低;肺组织MDA、XOD活力明显降低,SOD活力升高,IL-8、TNF-α水平均明显降低。结论：奥扎格雷钠可减轻大鼠肢体缺血再灌注后肺部的损伤。     

Amelioration of cyclosporine A-induced renal, hepatic and cardiac damages by ellagic acid in rats

Treatment with cyclosporine A has significantly improved long-term survival after organ transplantations. Cyclosporine A also causes a dose-related decrease in body functions in experimental animals and human beings. The generation of reactive oxygen species has been implicated in cyclosporine A-induced dysfunctions. The aim of this study was to determine the effects of ellagic acid on cyclosporine A-induced alterations in the kidney, liver and heart oxidant/antioxidant system. The control group was treated with placebo and subcutaneous injection of 0.5 ml isotonic saline + 0.5 ml slightly alkaline solution for 21 days. The cyclosporine A group received a subcutaneous injection of cyclosporine A (15 mg/kg) + 0.5 ml slightly alkaline solution for 21 days. The ellagic acid group was treated with a subcutaneous injection of 0.5 ml isotonic saline + ellagic acid (10 mg/kg) for 21 days. The cyclosporine A plus ellagic acid group received a subcutaneous injection of cyclosporine A + ellagic acid for 21 days. Ellagic acid and slightly alkaline solution were administered by gavage. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and reduced glutathione (GSH) levels, glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney, liver and heart tissues. While administration of cyclosporine A increased the MDA levels in kidney, liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. However, the simultaneously administration of ellagic acid markedly normalized the cyclosporine A-induced liver and heart MDA levels, liver CAT activities and GSH-Px activities of all samples. Cyclosporine A caused marked damages in the histopathological status of kidney, liver and heart tissues, which were partially ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cyclosporine A in transplantation treatment to improve the cyclosporine A-induced oxidative stress parameters and other adverse effects.     

The effect of PARS inhibition on ileal histopathology, apoptosis and lipid peroxidation in LPS-induced obstructive jaundice.

In our experimental study, we investigated the protective effect of 3-aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4: OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In Group 3; 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and then after 6h the rats were sacrificed. In Group 4; 10 mg kg(-1) 3-AB was administrated intraperitoneally at the fifth day and repeated daily for 3 days and at the eighth day, 10 mg kg(-1) LPS was injected intraperitoneally. In Group 5, 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and after 6h 10 mg kg(-1) 3-AB was administrated intraperitoneally and repeated daily for 3 days. At the eighth day, rats were sacrificed. Blood samples were taken for detection of serum MDA levels. Ileum samples were taken after relaparotomy for histopathological examination to evaluate the endotoxin-related intestinal injury and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities. There was marked destruction of villous and crypt epithelial cells and extensive apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the scores of intestinal mucosal damage and apoptotic cells were reduced significantly (P<0.05). On the other hand, the scores of intestinal mucosal damage and apoptotic cells were not improved in Group 5. After the administration of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if it was administrated before LPS. However, 3-AB failed to prevent the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if there was established endotoxemia in OJ.     

Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice

The effects of isoliensinine (IL), a bisbenzylisoquinoline alkaloid extracted from the Chinese traditional medicine seed embryo of Nelumbo nucifera Gaertn., on bleomycin (BLM)-induced pulmonary fibrosis in mice were investigated. Seventy-two male Kungming mice were divided randomly into eight groups as BLM-IL10, BLM-IL20, BLM-IL40, BLM-Sal, Sal-IL10, Sal-IL20, Sal-IL40 and Sal-Sal groups. BLM (0.1 mg in 0.05 ml saline per animal, once) or saline (0.05 ml per animal, once) was applied intratracheally, and IL (10, 20, 40 mg/kg) or saline was administered orally 3 times per day in the appropriate groups. Animals were sacrificed 14 days after intratracheal treatment. Lung tissue and serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta 1 (TGF-beta (1)) were determined by biochemical measurements and immunohistochemistry. BLM treatment resulted in a significant increase of the hydroxyproline content and an obvious lung histological injury as compared to the Sal-Sal group. Administration of IL remarkably suppressed the increase in hydroxyproline content and abated the lung histological injury induced by BLM. There was a decrease in SOD activity and an increase in MDA level in lung tissue and serum in the BLM-Sal group (p < 0.01 , p < 0.01, vs. Sal-Sal group, respectively). And IL could obviously enhance the SOD activity and decrease the MDA level in a concentration-dependent manner. Moreover, IL also significantly inhibited the overexpression of TNF-alpha and TGF-beta (1) induced by BLM. These results indicated that IL possessed a significant inhibitory effect on BLM-induced pulmonary fibrosis, probably due to its antioxidant and/or anti-inflammatory activities and inhibitory overexpressing TNF-alpha and TGF-beta (1) induced by BLM.     

EFFECTS OF SURFACE CHARACTERISTICS OF POTASSIUM TITANATE WHISKER SAMPLES ON ACUTE LUNG INJURY INDUCED BY A SINGLE INTRATRACHEAL ADMINISTRATION IN RATS

We compared in vivo biological effects, focusing on lung inflammatory responses after a single intratracheal administration of two types of well-characterized whiskers: potassium octatitanate and potassium hexatitanate, which have similar fiber sizes and chemical compositions, except their surface morphology. The geometrical mean of length (µm), width (µm), and geometric standard deviation (GSD) are: K 2 Ti 8 O 17 (PT1), 6.0[2.0], 0.35[1.51], having rough surface; K 2 Ti 6 O 13 (PT2), 5.0[2.18], 0.31[1.63], having smooth surface. Sixty male Wistar rats (8 wk old) under anesthesia were injected intratracheally with 2 doses of fibers (0.2 mg/0.5 ml/rat, 1.0 mg/0.5 ml/rat) or the same amount of saline solution (group C). Animals were sacrificed on days 1, 3, and 7 after fiber administration, and then the lung tissue and bronchoalveolar lavage (BAL) were collected. There were no obvious differences among the three groups in the yield of BAL fluid. Total protein concentration in BAL increased significantly from day 1; BAL fucose level increased significantly from day 3 in a dose-dependent manner, which gradually recovered by day 7 in groups PT1 and PT2. BAL total protein and fucose in group PT1 increased significantly compared with those in group PT2 at a dose level of 1.0 mg. A dose-independent increase ofβ -glucuronidase activity and decrease of superoxide dismutase activity were observed in both fibers. BAL tumor necrosis factor-α (TNF-α) increased significantly in animals treated with 1.0 mg dosage of PT1 and PT2 on day 1. However, BAL IL-1β did not show any marked change during the experimental period in animals treated with both fibers. On day 1, BAL cytokine-induced neutrophil attractants (CINC)/growth-related gene product (GRO) increased significantly in the PT1 group treated with 0.2 and 1.0 mg dosage. On day 3, the group treated with 1.0 mg PT1 showed significant increase of CINC/GRO compared with the group treated with 1.0 mg PT2, which recovered to the control level on day 7. Expression of various chemokine mRNAs (MCP-3, MIP-1α, RANTES, and eotaxin) increased in rats treated with PT1 or PT2 on day 1 and/or day 3. Increase of gene expression in the PT1 group was greater than that of the PT2 group at 0.2 mg dosage level. These results suggest that differences in the surface morphology of the whisker fibers of similar length and diameter, density, and chemical composition appear to be related to the facilitation of macrophage phagocytes in the macrophage-derived biological effects in acute lung injury induced by inhaled fibers.     

牛磺酸对肢体缺血再灌注致多器官损伤的预防作用研究

目的探讨牛磺酸在肢体缺血再灌注致多器官损伤的预防作用。方法（1）Wistar大鼠随机分三组：再灌注组，阻断双侧股动脉循环2h，再灌注5h；牛磺酸组，1～7d灌服20％牛磺酸3ml／只，后阻断双侧股动脉2h，再灌注5h；对照组，行假手术处理。（2）测定血白细胞总数、肝酶和心肌酶；观察红细胞SOD活性、血清谷胱甘肽（GSH）及肝、肺组织匀浆丙二醛（MDA）及器官的超微结构变化。结果再灌注组白细胞总数、心肌酶、肝酶较对照组显著降低（P〈0．05），其远隔器官超微病理示组织有弥漫性损伤。红细胞SOD及血清GSH较对照组显著下降，肝、肺组织匀浆MDA及肿瘤坏死因子含量显著增多（均P〈0．05）。而牛磺酸组病变明显改善。结论肢体缺血再灌注可激活中性粒细胞，释放氧自由基、肿瘤坏死因子，使机体处于全身炎症反应状态致远隔多器官损伤，牛磺酸可明显减轻多器官损伤。     

Pulmonary inflammation by ambient air particles is mediated by superoxide anion

Lung inflammation is a key response to increased levels of particulate air pollution (PM); however, the cellular mechanisms leading to this response remain poorly understood. We have previously shown that oxidants are critical mediators of the inflammatory response elicited by inhalation of ambient air particles. Here we tested the possible role of a specific oxidant, superoxide anion, by using the membrane-permeable analog of superoxide dismutase, Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP). Adult Sprague-Dawley rats were instilled with either urban air particles (UAP) or saline. MnTBAP-treated rats received 10 mg/kg (ip) MnTBAP 2 h prior to exposure to UAP. Recruitment of inflammatory cells into bronchoalveolar lavage was evaluated 4 h after instillation. Rats exposed to UAP showed significant increases in the total cell number (8.9 +/- 0.6 x 10(6); sham: 5.1 +/- 0.6 x 10(6), p < .02), the numbers of polymorphonuclear leukocytes (26 +/- 4%; sham: 6 +/- 1%, p < .0001), protein levels (1.2 +/- 0.5 mg/ml, sham: 0.4 +/- 0.1 mg/ml, p < .001), and a trend of increase in myeloperoxidase levels (5 +/- 1; sham: 2 +/- 1 mU/ml) in bronchoalveolar lavage (BAL). Pretreatment with MnTBAP at a dose that prevented UAP-induced increases in oxidants effectively prevented increase in BAL cells (2.7 +/- 0.6 x 10(6), p < .0001 vs. UAP), PMN influx into the lungs (4 +/- 3%, p < .0001 vs. UAP), and increase in myeloperoxidase (2 +/- 1 mU/ml) and protein levels in BAL (0.1 +/- 0.1 mg/ml). These data indicate that superoxide anion is a critical mediator of the inflammatory response elicited by PM deposition in the lung.     

Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-kappaB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-kappaB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-kappaB, and MPO activities were significantly reduced in 3-AB group at each time point (p<0.05). Plasma MMP-9 increased maximally at 4h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-kappaB increased maximally at 24h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-kappaB and the infiltration of neutrophils in ischemic stroke.     

右美托咪定对肢体缺血再灌注诱发肺损伤的影响

目的:评价右美托咪定对肢体缺血再灌注诱发肺损伤的影响。方法:择期行择期行下肢手术患者40例,性别不限,年龄40~65岁,体质量50~85 kg,ASA分级Ⅰ或Ⅱ级。采用随机数字表法,将其分为2组(n=20):对照组(C组)和右美托咪定组(D组)。麻醉诱导后气管插管,机械通气,采用静吸复合麻醉。麻醉诱导后,D组静脉输注右美托咪定1 μg·kg^-1(加入100 ml生理盐水),C组给予生理盐水,于止血带充气前滴注完毕。于麻醉诱导前(T₁)、止血带充气(T₂)、60 min(T₃)、90 min(T₄)时,止血带放气后5 min(T₅)、30 min(T₆)时采集桡动脉血样,行血气分析,计算氧合指数和呼吸指数。测定血浆白介素6(IL-6)、丙二醛(MDA)及细胞间黏附分子(ICAM-1)的浓度。结果:与C组相比,D组T_2~5时RI升高(P<0.05),而OI差异无统计学意义(P>0.05);D组T_2~6时血浆IL-6、MDA及ICAM-1的浓度降低(P<0.05)。结论:右美托咪定可减轻肢体缺血再灌注诱发的肺损伤,其机制与抑制炎性反应有关。     

阿米洛利对大鼠肺缺血再灌注损伤的保护作用

目的观察阿米洛利对大鼠肺缺血再灌注损伤(LIRI)的保护作用及其可能机制。方法建立大鼠在体肺缺血再灌注模型。将雄性Wistar大鼠54只随机分为手术对照组(C组)、缺血再灌注组(IR组)、阿米洛利组(A组)。每组分别在缺血45min,再灌注60、120min3个时点处死6只大鼠,留取血浆和右肺组织,测定肺组织湿干质量比值(W/D)、髓过氧化物酶(MPO)活性,肺组织中细胞凋亡指数(AI)及血清丙二醛(MDA)含量,并进行肺组织病理学检查。结果再灌注期间IR组肺组织W/D、MPO活性、AI、血清MDA均升高,而预先给予阿米洛利干预后可以减弱缺血再灌注诱导上述指标的升高。肺组织病理学检查显示阿米洛利预先给药减轻肺缺血再灌注损伤。结论阿米洛利对肺缺血再灌注损伤有保护作用,可能与其抑制氧自由基生成、中性粒细胞浸润及细胞凋亡有关。     

丹参大鼠肢体缺血再灌注后多器官水肿的预防作用

【摘要】 目的：探讨氧化应激（oxidative stress）在大鼠肢体缺血再灌注（LIR）致多器官水肿中的作用及丹参的影响。方法：Wistar大鼠24只随机分为三组（n=8）:对照组（C组）、缺血再灌注组（I/R组）和丹参预处理组(SM组)。以止血带法制作大鼠肢体缺血再灌注模型,SM组在再灌注前30min经尾静脉推注丹参注射液5ml／kg。手术准确留取每只动物的心、肝、肾、肺、脑、肠及骨骼肌组织各1g,恒温烘干后称其干重并计算各标本的湿干重比值(W/D)。采用生物化学方法测定血浆SOD、XOD活性及MDA含量。光镜下观察各组织的形态学变化。结果：LIR后各组织W/D均增加（P<0.01或P<0.05）,血浆SOD活性降低而XOD活性和MDA含量增加（P<0.01或P<0.05）,各组织镜下可见不同程度的结构紊乱、组织间隙增宽和炎细胞浸润等病理改变。而SM组与单纯再灌注组比较,血浆SOD活性回升而XOD活性和MDA含量降低（P<0.01或P<0.05）,镜下组织病理学变化有所减轻。结论：大鼠肢体缺血再灌注可导致多器官水肿,氧化应激是其重要机制之一。丹参可通过抗氧化在此过程中发挥抗水肿作用。     

奥扎格雷钠对大鼠肢体缺血再灌注所致肺损伤的保护作用

目的:探讨奥扎格雷钠( Ozagrel sodium)对大鼠肢体缺血再灌注后肺损伤的影响.方法:将60只雄性SD大鼠随机分成正常对照组、缺血再灌注组和奥扎格雷钠组,建立大鼠肢体缺血再灌注损伤模型.用光镜和电镜观察肺组织形态学改变和超微结构改变,用竞争放射免疫分析法测定血浆血栓素A2(TXA2)代谢产物血栓素B2(TXB2)和前列环素(PGI2)代谢产物6-酮-前列腺素F1α(6-Keto-PGF1α),比色法测定肺组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和黄嘌呤氧化酶(XOD),双抗体夹心ABC-ELISA法测定肺组织中白细胞介素(IL)-8和肿瘤坏死因子(TNF)-α,并进行比较.结果:与缺血再灌注组相比,奥扎格雷钠组肺血管扩张、炎性细胞聚集、线粒体水肿、内膜下基底膜水肿、内皮细胞肿胀等情况明显减轻;血浆TXB2和6-Keto-PGF1α含量显著降低;肺组织MDA、XOD活力明显降低,SOD活力升高,肺组织IL-8、TNF-α水平均明显降低.结论:奥扎格雷钠可减轻大鼠肢体缺血再灌注后肺部的损伤.     

大鼠肢体缺血再灌注早期血栓前状态及其干预研究

目的:探讨大鼠急性下肢缺血再灌注早期血栓的形成情况,对比前列地尔(凯时)和低分子量肝素对此的干预作用。方法:将大鼠随机分为假手术组、下肢缺血再灌注组、下肢缺血再灌注+肝素组、下肢缺血再灌注+前列地尔组。夹闭大鼠股动脉并用张力带绑扎下肢,建立急性下肢缺血再灌注大鼠模型。观察急性下肢缺血再灌注大鼠血小板膜糖蛋白CD41和血管内皮细胞血栓调节蛋白(TM)的表达以及经药物干预后的变化。结果:缺血再灌注组大鼠血小板膜糖蛋白CD41表达高于假手术组(P<0.05);两个药物组CD41表达均低于缺血再灌注组(P<0.05);而两个药物组间血小板膜糖蛋白CD41表达差异无显著性。缺血再灌注组大鼠血管内皮血栓调节蛋白(TM)表达低于假手术组(P<0.05);两个药物组TM表达均高于再灌注组(P<0.05),且肝素组高于前列地尔组(P<0.05),结论:急性下肢缺血再灌注会导致大鼠血栓前状态的形成,而预防性给予前列地尔和肝素可有效抑制此状态形成,二者作用环节不同,抗凝效果比较有待进一步研究。