The effect of a Rho kinase inhibitor Y-27632 on superoxide production, aggregation and adhesion in human polymorphonuclear leukocytes

We investigated the involvement of p160ROCK (a Rho-associated coiled coil-forming protein kinase), one of Rho kinases on superoxide anion production (O(2)(-) production), aggregation and adhesion of human polymorphonuclear leukocytes under physiological condition, using a selective p160ROCK inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632). Y-27632 inhibited the O(2)(-) production stimulated by phorbol-12-myristate-13-acetate (PMA) in a dose-dependent manner. Stauroprorine blocked the PMA-induced O(2)(-) production while wortmannin did not. Y-27632 also inhibited the O(2)(-) production by guanosine 5'-O-(3-thiotriphosphate) (GTP(gamma)S) 100 microM. N-formyl-Met-Leu-Phe (fMLP)-induced O(2)(-) production was not influenced by Y-27632, but was inhibited by wortmannin. The enhanced O(2)(-) production by Ca-ionophore A23817 and thapsigargin was not inhibited by Y-27632. Y-27632 did not change the basal intracellular Ca(2+) concentration nor its elevation stimulated by fMLP. Polymorphonuclear leukocytes aggregation induced by PMA was dose-dependently decreased by Y-27632 while their aggregation stimulated by fMLP was enhanced by the agent. Polymorphonuclear leukocytes adhesion induced by PMA or fMLP was not influenced by Y-27632.These results suggest that p160ROCK is involved in the PMA-induced O(2)(-) production and aggregation in human polymorphonuclear leukocytes. This kinase might locate in downstream of protein kinase C in polymorphonuclear leukocytes.     

Protective effect of a novel antioxidant non-steroidal anti-inflammatory agent (compound IA) on intestinal viability after acute mesenteric ischemia and reperfusion

Reactive oxygen species play an important role in the basic pathophysiology of ischemia-reperfusion injury. We investigated whether the administration of a novel non-steroidal anti-inflammatory compound with antioxidant properties, the compound [5-(2-amino-ethylamino)-1-phenyl-2-pentanone] (compound IA), has a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, compound IA was administered intravenously and the clamp was removed allowing reperfusion. At 60 min after reperfusion, animals were sacrificed and a 10 cm section of terminal ileum was resected. The outcome was evaluated by histopathologic assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, the mucosal damage was less in IA-treated rats compared with the control group. Moreover, the number of polymorphonuclear leukocytes in intestinal mucosa was significantly lower in IA group. Compound IA resulted in a statistically significant reduction of the concentration of small intestine tissue malondialdehyde, compared to those of controls. Administration of compound IA decreased the mucosal damage in rats that were subjected to 60 min of ischemia followed by 60 min of reperfusion. The mechanism of compound IA action is considered to be mediated via its potent antioxidant, free radical scavenging activities and inhibition of polymorphonuclear leukocytes infiltration.     

川芎嗪对大鼠肝脏缺血再灌注损伤的保护作用

目的：研究川芎嗪对大鼠肝脏缺血再灌注损伤的保护作用及其机制。方法：SD大鼠随机分为5组：空白对照组、假手术组、缺血再灌注组、生理盐水组和川芎嗪组。其中空白对照组大鼠直接处死;假手术组开腹后60 min关闭腹腔;缺血再灌注组阻断70%肝血流60 min,再灌注4 h;生理盐水组予腹腔内注射生理盐水8 ml/kg,30 min后阻断70%肝血流60 min,再灌注4 h;川芎嗪组予腹腔内注射川芎嗪80 mg/kg,30 min后阻断70%肝血流60 min,再灌注4 h。速率法测血清丙氨酸氨基转移酶（alanine aminotransferase,ALT）和天冬氨酸氨基转移酶（aspartate aminotransferase,AST）活性,酶联免疫吸附法（ELISA）测血白介素-1（IL-1）、白介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）水平。苏木素-伊红染色观察肝脏病理改变。结果：川芎嗪组血清ALT、AST、IL-1和TNF-α水平均比缺血再灌注组和生理盐水组明显降低（P〈0.05）,而IL-10则明显高于缺血再灌注组和生理盐水组（P〈0.05）。病理结果显示,川芎嗪组大鼠肝细胞损伤较缺血再灌注组和生理盐水组为轻。结论：川芎嗪对大鼠肝脏缺血再灌注损伤具有保护作用,其机制可能与抑制炎性细胞因子生成及促进抗炎细胞因子表达有关。     

丙泊酚对大鼠肝脏缺血再灌注损伤Bcl-2和P53表达的影响

目的探讨丙泊酚对大鼠肝脏缺血再灌注损伤时Bcl-2和P53表达的影响及其保护作用。方法健康成年雄性SD大鼠54只,随机分为3组:假手术组(Ⅰ组)、缺血再灌注组(Ⅱ组)、丙泊酚组(Ⅲ组)。每组根据再灌注时间不同又分为3个时间段(1、2、3h)。制作70%肝脏缺血再灌注模型,实验结束后即刻取肝左叶做标本。用免疫组织化学法检测Bcl-2与P53蛋白表达量,原位细胞凋亡检测(TUNEL)法检测肝细胞凋亡指数(AI),光镜下观察肝组织的病理学变化。结果与Ⅰ组比较,Ⅱ、Ⅲ组肝组织Bcl-2、P53蛋白含量、凋亡指数差异均有统计学意义(P<0.05);与Ⅱ组比较,Ⅲ组Bcl-2蛋白表达增加、P53蛋白表达和AI减少(P<0.05);光镜下Ⅲ组的肝细胞病理学变化轻于Ⅱ组。结论丙泊酚可以通过调节Bcl-2、P53蛋白表达,使肝细胞凋亡减轻,从而对大鼠缺血再灌注肝脏有一定的保护作用。     

Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632

The possible contribution of Rho/Rho-kinase signalling in oleic acid (100 mg kg-1, i.v., for 4 h)-induced lung injury was investigated in rats. Furthermore, the possible protective effect of the administration of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 0.5-5 mg kg-1, i.v., 15 min before the administration of oleic acid), was also examined. Western blot analysis as well as histopathological examination revealed that Rho-kinase (ROCK-1 and ROCK-2) was upregulated in lungs obtained from oleic acid-administrated rats. In addition, the markers of oxidative and nitrosative stress, i.e., malondialdehyde, myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate, in serum and lung tissue were also increased in the injury group. Treatment of rats with 5 mg kg-1 Y-27632 reversed the oleic acid-induced lung damage, which was demonstrated by histopathological assessment and confirmed in Western blot experiments: ROCK-blots were more intense in the oleic acid group than in control and Y-27632 treatment reversed ROCK upregulation. In addition, malondialdehyde, myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate were also normalized after the administration of Y-27632 (0.5 mg kg-1 and 5 mg kg-1). These findings suggest that ROCK-1 and ROCK-2 are involved in oleic acid-induced lung damage in rats, and that inhibition of this enzyme by Y-27632 may have a protective effect against such damage. Consequently, Rho kinase inhibitors may be potential therapeutic agents in the treatment of acute respiratory distress syndrome (ARDS).     

Protective effect of the 5-lipoxygenase inhibitor ardisiaquinone A on hepatic ischemia-reperfusion injury in rats

The protective effects of the 5-lipoxygenase inhibitor ardisiaquinone A, a compound isolated from Ardisia sieboldii, on hepatic ischemia-reperfusion (I/R) injury was studied in rats. Hepatic I/R injury was induced by occlusion of the portal vein and the hepatic artery for 60 min, followed by reperfusion for 24 h. The content of leukotriene B (4) (LTB (4)) in the liver increased during ischemia. Serum alanine aminotransferase (ALT) levels, a marker of hepatic parenchymal cell injury, and hepatic myeloperoxidase (MPO) activity, a marker of neutrophil accumulation, significantly increased 6 - 9 h after reperfusion. Treatment with ardisiaquinone A (0.1 - 2 mg/kg, i. p.) 30 min prior to ischemia dose-dependently prevented the increase in LTB (4) content during ischemia (ID (50) = 0.645 mg/kg) with a slightly higher potency than that of AA-861 (ID (50) = 0.728 mg/kg), a known reference 5-lipoxygenase inhibitor. Ardisiaquinone A also attenuated the increase in MPO activity and serum ALT levels at 6 h after reperfusion (ID (50) = 1.71 mg/kg and 4.28 mg/kg, respectively). These protective effects were more efficient than those of AA-861 (ID (50) = 1.86 mg/kg and no effect, respectively), LY255283 (ID (50) = 18.1 mg/kg and 11.5 mg/kg, respectively), and ONO-4057 (ID (50) = 8.38 mg/kg and 9.44 mg/kg, respectively), which are LTB (4) receptor antagonists. These results suggest that ardisiaquinone A may protect the liver against damage due to I/R in rats.     

Effect of intraportal verapamil infusion on hepatic ischemia-reperfusion injury.

Removal of free oxygen radicals, generated during reperfusion of an ischemic organ by scavengers protects the tissue from reperfusion injury. The calcium channel blocker verapamil is an effective cytoprotective agent, preventing against reperfusion injury. The effects of verapamil were investigated previously using hepatic, renal or cardiac ischemia-reperfusion injury models. We investigated the effects of intravenous and intraportal administration of verapamil in prevention from the injury caused by free oxygen radicals generated during hepatic ischemia-reperfusion in rats. Thirty six male Sprague-Dawley rats after laparotomy were subjected to hepatic ischemia for 30 and 45 min followed by 60 min of reperfusion. Two minutes before ischemia the rats were pretreated by intravenous or intraportal administration of verapamil. The levels of glutathione and thiobarbituric acid reacting substances (TBARs) referred to as malonyldialdehyde (MDA) and the serum levels of transaminases were measured in liver tissue 1 and 24 h after the onset of reperfusion. Statistical analysis of the data by Student's t-test showed statistically significant differences between the group pretreated intraportally with verapamil and the other groups. Verapamil given intraportally exerted more beneficial effect. Therefore, we conclude that intraportal verapamil administration reduces the ischemia-reperfusion injury caused by free oxygen radicals.     

丙泊酚对大鼠肠缺血再灌注损伤时肝细胞凋亡及Caspase-3的影响

目的探讨丙泊酚对大鼠肠缺血再灌注损伤时肝细胞凋亡及Caspase-3的影响。方法成年健康Wistar大鼠42只,随机分为3组:实验对照组(C组,6只)、肠缺血再灌注组(IR组,18只)、丙泊酚干预组(P组,18只)。各组根据再灌注时间分为1,3,6h三个时相。通过夹闭肠系膜上动脉制作肠缺血再灌注损伤模型,实验结束后即刻取肝左叶做标本。用免疫组织化学法检测Caspase-3蛋白表达量,末端转移酶标记技术(TUNEL)法检测肝细胞凋亡指数(AI)。结果与C组比较,IR组和P组肝组织Caspase-3蛋白含量、AI均增加(P<0.05);与IR组比较,P组Caspase-3蛋白表达减少、AI减少(P<0.05)。结论丙泊酚可以下调大鼠肠缺血再灌注时Cas-pase-3蛋白表达,使肝细胞凋亡减轻,从而对肝损伤有一定的保护作用。     

腺苷2A受体在小鼠全肝缺血-再灌注损伤中的表达及意义

目的 探讨在小鼠全肝缺血-再灌注(I-R)前后肝组织内腺苷2A受体的动态表达趋势,以及与肝脏组织炎症反应的关系.方法 分别检测缺血前、缺血20 min、再灌注0、1、3、6、12、18、24 h后肝脏A2AR蛋白表达和肿瘤坏死因子α(TNF-α)、巨噬细胞炎性蛋白2(MIP-2)、细胞间黏附分子(ICAM-1)含量以及组织髓过氧化物酶(MPO)活性的变化.结果 A2AR表达于再灌注后12 h达高峰,随后逐渐下降,再灌注24 h降至正常以下水平.而TNF-、MIP-2和ICAM-1含量于再灌注后表达逐渐增高,3～6 h达到高峰,随后逐渐降低.MPO的活性趋势与炎性因子基本一致.结论 I-R后组织炎症可能诱导了A2AR表达升高,从而抑制炎性因子的表达及组织炎性损伤.     

缩宫素对大鼠肝脏缺血-再灌注损伤的保护作用及其机制

目的 探讨缩宫素对大鼠肝脏缺血-再灌注(I-R)损伤的保护作用及可能的机制.方法 将48只雌性SD大鼠随机均分为假手术(S)组、I-R组和缩宫素处理(OT)组.建立大鼠70%I-R模型,缺血时间1 h.OT组分别于术前12 h,15 min及再灌注时经腹腔注射缩官索0.5 mg/kg,S组及I-R组在相同时间注射等量生理盐水.各组大鼠分别于肝脏再灌注后2和6 h处死,取肝脏及血液标本,检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肿瘤坏死因子α(TNF-α)以及肝脏组织超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)的活性及丙二醛(MDA)含量,并分别检测肝组织中核因子κB(NF-κB)的表达和肝脏组织的病理改变.结果 与I-R组相比,OT组的ALT、AST、TNF-α水平及MPO、NF-κB阳性表达明显降低(P<0.05),肝脏病理损伤较轻,但是MDA及SOD变化不明显.结论 缩宫素对大鼠肝脏I-R损伤具有保护作用.其机制可能与抑制炎症因子产生及活化有关.     

依达拉奉抑制缺血再灌注肾脏ICAM-1的表达

目的探讨依达拉奉对大鼠肾脏缺血再灌注后ICAM-1表达的影响。方法将24只雄性Wistar大鼠随机分为假手术组(S组)、缺血再灌注组(I组)、依达拉奉治疗组(E组),其中S组和E组大鼠均夹闭双侧肾蒂45 min、再灌注24 h制成肾缺血再灌注损伤动物模型。缺血前和再灌注即刻,E组经尾静脉给予依达拉奉3 mg/kg,S组和I组经尾静脉给予等量生理盐水。于再灌注24 h取左肾苏木精-伊红染色观察炎症细胞浸润情况,免疫组织化学观察ICAM-1表达。结果光镜下S组结构正常,I组中大量炎症细胞浸润肾间质,EB组炎症细胞浸润减少;免疫组织化学显示,I组中ICAM-1表达较S组上升,EB组则较I组下降(P<0.05)。结论依达拉奉抑制大鼠肾脏缺血再灌注损伤时ICAM-1的表达。     

用乌司他丁抑制炎症反应减轻大鼠移植肝再灌注损伤的实验研究

目的 研究乌司他丁（ulinastatin,UTI）对移植肝再灌注损伤的保护作用及相关机制.方法 建立Sprague-Daw-ley同系大鼠肝移植（OLT）模型,受体分为3组,每组8只大鼠：假手术组、对照组和乌司他丁组.假手术组大鼠仅接受麻醉、开腹、肝周韧带游离及关腹操作;乌司他丁组及对照组大鼠建立OLT模型,门静脉开放后,乌司他丁组大鼠经尾静脉注射乌司他丁1×104 U/kg,对照组大鼠注射等量生理盐水.再灌注后6及24 h每组分别处死4只大鼠,获取下腔静脉血标本及肝脏标本.检测各组大鼠血清ALT水平及肝组织形态学变化、肝细胞凋亡情况;用免疫组化方法检测肝脏Kupffer细胞浸润,用荧光定量RT-PCR检测肝脏肿瘤坏死因子（tumor necrosis factor,TNF）-α、白细胞介素（interleukin,IL）-6、IL-1β及单核细胞趋化蛋白（monocyte chemoattractant protein,MCP）-1mRNA表达水平,用酶联免疫吸附试验检测受体血清内上述炎症介质含量;用蛋白质印迹技术检测肝脏内核因子（nuclear factor,NF）-κB亚单位P65磷酸化水平.结果 与对照组相比,在同一时点检测乌司他丁组大鼠血清ALT水平明显降低（P＜0.01）,肝脏组织学损伤情况明显改善（P＜0.01）,肝细胞凋亡明显减少（P＜0.01）;肝脏内TNF-α、IL-1β、IL-6、MCP-1的mRNA表达降低（P＜0.01）,血清内上述炎症介质含量明显降低（P＜0.01）;P65磷酸化水平明显下降.结论 乌司他丁能够减轻大鼠移植肝再灌注损伤,其机制可能与其抑制再灌注后炎症反应有关.     

A novel antioxidant non-steroidal anti-inflammatory agent protects rat liver against ischemia-reperfusion injury

Liver ischemia followed by reperfusion is an important and common clinical event. A major mechanism is leukocyte adhesion to endothelium followed by release of reactive oxygen metabolites. The aim of this study was to determine the effects of a novel antioxidant ethylenediamine derivative with anti-inflammatory properties (compound IA) on an imitated clinical setting of acute hepatic ischemia-reperfusion injury. Eight groups of rats were subjected to a model of hepatic ischemia that was produced by occluding for 30 min the portal vein and hepatic artery. At the end of ischemia, compound IA was administered intravenously and the clamps were removed allowing reperfusion for 60 min or 24 h. The effect of compound IA was evaluated by histopathological examination, lipid peroxidation and plasma levels of liver enzymes. Administration of compound IA resulted in significantly less histological damage in liver tissue after 30-min ischemia followed by 60-min and 24-h reperfusion. Ischemia followed by 60 min of reperfusion increased lipid peroxidation compared to the sham-operated and the non-ischemic group. This increase was attenuated in the group treated with compound IA. Serum enzyme levels were significantly higher in the reperfusion groups compared to the non-ischemic groups and diminished after treatment. Compound IA exerted a protective effect on hepatic reperfusion injury in rats. Compound IA is believed to act by means of its potent antioxidant and anti-inflammatory activities.     

N-乙酰半胱氨酸对肝缺血再灌注损伤大鼠Toll样受体4表达的影响

目的：探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)对肝缺血再灌注(ischemic reperfusion,I/R)损伤大鼠Toll样受体4(Toll-like receptor 4,TLR4)表达的影响。方法：Wistar大鼠随机分为3组：假手术组(P)、I/R组、I/R+NAC组。P组只开腹不阻断肝血流,另2组阻断大部肝血流后再灌注,其中I/R+NAC组再灌注前5 min尾静脉给予300 mg/kg NAC。各组分别检测不同时间点的血丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、脂多糖(LPS)与肝组织TLR4 mRNA及其蛋白。结果：在各时间点,P组血ALT,AST,LPS和肝绍织TLR4表达无显著差异；另2组较P组均有显著升高,但I/R+NAC组各指标升高低于I/R组。肝组织TLR4 mRNA表达在I/R组从3 h起显著增强并维持高表达,而I/R+NAC组各时相无显著变化；但两者TLR4蛋白表达变化类似,都在6,24 h表达显著增强。结论：LPS及其TLR4参与了I/R肝损伤的病理过程；NAC减弱肠源性LPS及其启动的TLR4炎症信号通路而保护缺血再灌注肝损伤。     

Effects of defibrotide,a novel oligodeoxyribonucleotide,on ischaemia and reperfusion injury of the rat liver

1. The purpose of this study was to investigate the protective effects of defibrotide, a single-stranded polydeoxyribonucleotide, on ischaemia-reperfusion injury to the liver using a rat model. 2. Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte-endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3. Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4. A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5. We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.     

肝移植患者术中氧自由基相关指标的变化

目的：研究在肝移植术中氧自由基对肝脏缺血再灌注损伤的作用。方法：测定比较18例肝移植患者术前、无肝期、再灌注后1h血浆中脂质过氧化物(LPO)、超氧化物歧化酶(SOD)、总抗氧化能力(TAC)、一氧化氮水平(NO)，分析其变化。结果：再灌注后LPO和TAC下降，SOD和NO升高。结论：氧自由基在肝移植缺血再灌注损伤中有重要作用，再灌注后，激活了保护机制，手术中输血及某些药物的使用也可以减轻自由基损害，对机体具有保护作用。     

Heme oxygenase-1 could mediate the protective effects of hyperbaric oxygen preconditioning against hepatic ischemia-reperfusion injury in rats

1. Heme oxygenase 1 (HO-1) has been shown to play a pivotal role in the maintenance of cellular homeostasis when the liver undergoes sublethal stress, such as ischaemia-reperfusion (I/R) injury. In the present study, we investigated the protective role of HO-1 in hyperbaric oxygen (HBO) preconditioning against liver injury after I/R. 2. A total hepatic ischaemia (30 min) and reperfusion (60 min) injury model in rats was used in the present study. Preconditioned groups were exposed to HBO 24 h prior to the induction of I/R injury. Other groups were injected with zinc protoporphyrin IX (ZnPP) intraperitoneally 1 h before I/R to inhibit HO-1 activity. At the end of the reperfusion period, blood and liver samples were collected for the analysis of liver injury markers, morphological changes, and HO-1 expression and activity in the liver. 3. In untreated rats, I/R induced an increase in hepatic injury markers, such as plasma transaminases, inflammatory cytokines (tumour necrosis factor-α and interleukin-1β), and tissue malondialdehyde. However, HBO preconditioning attenuated the I/R-induced increases in these hepatic injury markers, and prevented both the necrosis and apoptosis of hepatocytes induced by I/R injury. Furthermore, HBO preconditioning significantly increased HO-1 mRNA and protein levels in the liver. In rats in which HO-1 activity had been inhibited with ZnPP pretreatment, the protective effects of HBO preconditioning against I/R injury were abolished. 4. In conclusion, HBO preconditioning can protect the liver against I/R injury and it appears that this effect might be mediated by the induction of HO-1.     

双苯氟嗪对大鼠局灶性脑缺血再灌注后E-选择素、P-选择素和细胞间黏附分子-1表达的影响

目的研究双苯氟嗪对大鼠脑缺血再灌注后E-选择素(E-selectin)、P-选择素(P-selectin)和细胞间黏附分子-1(ICAM-1)表达及中性粒细胞浸润的影响。方法采用Zea-Longa线栓法建立大鼠局灶性脑缺血再灌注模型。采用HE染色、免疫组化、流式细胞术以及生化的方法，观察双苯氟嗪对大鼠缺血再灌注后脑组织形态学、P-选择素、E-选择素和ICAM-1表达以及髓过氧化酶(MPO)活性的影响。结果双苯氟嗪可改善缺血再灌注后脑损伤的形态学表现；降低P-选择素、E-选择素和ICAM-1的表达以及MPO的活性。结论双苯氟嗪减轻缺血再灌注后炎症反应，对缺血再灌注性脑损伤具有保护作用。     

三氯化钆对肝缺血再灌注损伤的影响

目的探讨库普弗细胞(KCs)功能封闭对肝缺血再灌注损伤的影响。方法雄性Wistar大鼠随机分为三组:对照组:只开腹,不做其他任何处理;缺血再灌注(I/R)组:术前24,48h经鼠尾静脉注射等量0.9%氯化钠溶液(pH3.5);三氯化钆(GdCl3)+I/R组:术前24,48h经鼠尾静脉注射0.5%GdCl3溶液(10mg/kg)。第3天进行肝脏部分缺血再灌注手术(约70%肝血流)。缺血45min后,再灌注3,6h,乙醚麻醉后,开腹进行无菌无热源腹主动脉采血,肝左叶用10%甲醛溶液固定,肝中叶包裹后置-70℃冰箱保存,制备匀浆用于丙二醛(MDA)、谷胱甘肽(GSH)、肿瘤坏死因子(TNF)-α含量的测定。结果缺血45min后,再灌注3,6h,GdCl3+I/R组血浆丙氨酸转氨酶活性、肝脏MDA及TNF-α含量均显著低于I/R组(P<0.01),而GSH含量则明显高于肝损伤组(P<0.01)。结论GdCl3可保护肝缺血再灌注损伤。     

Effects of 8-(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4,5] decane dihydrochloride monohydrate (Y-8845) on carbon tetrachloride-induced liver injury

The effects of 8-(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4, 5] decane dihydrochloride monohydrate (Y-8845) on carbon tetrachloride (CCl4)-induced liver injury were investigated in rats. CCl4-induced attenuation of the plasma cyclic AMP (cAMP) response to glucagon stimulation was significantly prevented by pretreatment with Y-8845. Y-8845 also effectively suppressed the increases in the activities of serum transaminases as well as the decreases in microsomal glucose-6-phosphatase activity and microsomal cytochrome P-450 concentrations induced by CCl4. In rats at 72 hr after CCl4 administration, the plasma cAMP response to glucagon, microsomal glucose-6-phosphatase activity and P-450 concentration were all below the control level. Y-8845 treatment after CCl4 administration rectified these reductions to nearly normal levels. Furthermore, Y-8845 stimulated DNA synthesis during liver regeneration after CCl4 intoxication. These results demonstrate that Y-8845 has a protective effect against CCl4-induced injury in the liver and a stimulating effect on the recovery of the damaged liver.