异搏定、能量合剂对小肠缺血再灌注损伤的保护作用

目的研究不同肠系膜上动脉灌注液对缺血小肠功能改变的影响。方法制成兔小肠缺血再灌注模型。分别观察缺血即刻、完全阻断６０分钟和再灌注３０分钟时小肠组织线粒体游离Ｃａ２＋浓度和小肠组织ＡＴＰ含量结果完全阻断６０分钟时,异搏定组Ｃａ２＋浓度（２．９７６±０．４１０）ｎｍｏｌ／ｍｇ·ｐｒｏｔ及该组和能量合剂组ＡＴＰ含量（０．５６４±０．０９７,０．５９４±０．０９０）μｍｏｌ／ｇ干重明显优于生理盐水组（Ｐ＜０．０１）;再灌注３０分钟时,两组Ｃａ２＋浓度（２．４０１±０．３２３,３．８４７±０．６１０）ｎｍｏｌ／ｍｇ·ｐｒｏｔ和ＡＴＰ含量（０．８０６±０．１８４,０．７４９±０．２８０）μｍｏｌ／ｇ干重均优于生理盐水组（Ｐ＜０．０１）。结论异搏定和能量合剂可以显著改善缺血小肠的功能改变。     

己酮可可碱对沙鼠全脑缺血／再灌注的保护作用

目的　观察己酮可可碱 (PTX)对沙鼠全脑缺血 /再灌注模型的作用效果 ,并对其作用机制进行初步探讨。方法　夹闭双侧颈动脉 ,诱导沙鼠全脑缺血 ,30分钟后松夹 ,再灌注 90min。在缺血诱导时 ,静脉给予 2 5mg·kg-1,或者 5 0mg·kg-1的PTX ;另一组于再灌注开始时静脉输注 2 5mg·kg-1的PTX。假手术组和对照组输入相同容积的 0 9%NaCl。再灌注开始时以 0 2 %伊文思兰 1ml·10 0g-1对所有沙鼠腹腔注射。实验结束时断头取脑 ,- 70℃冰箱保存 ,进行脑水肿定量、脑组织超氧化物歧化酶 (SOD)活性、丙二醛 (MDA)含量测定及脑组织伊文思兰含量测定。结果　与对照组相比 ,在缺血诱导时或再灌注开始时输注 2 5mg·kg-1PTX明显减轻沙鼠脑水肿的程度 (P <0 0 5或0 0 1) ,脑组织脂质过氧化产物MDA含量显著降低 (P <0 0 5或 0 0 1) ,脑组织中SOD的活性明显升高 (P <0 0 5或 0 0 1) ,脑组织伊文思兰含量显著降低 (P <0 0 5或 0 0 1)。 5 0mg·kg-1PTX输注对沙鼠脑缺血 /再灌注损伤无保护作用 ,其中 3只沙鼠死于低血压休克。结论　在血液动力学稳定的前提下 ,PTX对脑缺血 /再灌注损伤的保护作用可能与其提高脑血流量 ,抑制超氧阴离子产生 ,以及对血管内皮细胞的保护作用有关     

已酮可可碱对沙鼠全脑缺血/再灌注的保护作用

目的观察已酮可可碱(PTX)对沙鼠全脑缺血／再灌注模型的作用效果,并对其作用机制进行初步探讨。方法夹闭双侧颈动脉,诱导沙鼠全脑缺血,30分钟后松夹,再灌注90min。在缺血诱导时,静脉给予25mg·kg     

Protective effect of N-acetylcysteine on renal ischemia/reperfusion injury in the rat

BACKGROUND: Oxygen free radicals are important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). METHODS: The protective effect of N-acetylcysteine (NAC) against the damage inflicted by reactive oxygen species during renal I/R was investigated in Wistar Albino rats using biochemical parameters. Animals were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by lh of reperfusion. N-acetylcysteine (150 mg/kg, i.p.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. For biochemical analysis, the lipid peroxidation product malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO) were tested. Serum creatinine and BUN concentrations were measured for the evaluation of renal function. RESULTS: I/R induced nephrotoxicity, as evidenced by increases in BUN and creatinine, was reversed by NAC. The decrease in GSH and increases in MDA, MPO and PO induced by I/R indicated that renal injury involves free radical formation. CONCLUSIONS: Since NAC reversed these oxidant responses, and protected rat renal proximal tubules from in vitro simulated reperfusion injury, it seems that NAC protects kidney tissue against oxidative damage.     

己酮可可碱对肝脏缺血再灌注损伤保护作用的实验研究

目的　观察大鼠肝脏缺血再灌注后肿瘤坏死因子 -α (TNF α)早期释放及核因子κB(NFκB )活化对炎性介质表达和中性粒细胞浸润的影响。探讨其对肝缺血再灌注损伤的意义。方法　建立大鼠肝脏部分热缺血模型 ,己酮可可硷 (PTX )组于缺血前 1h腹腔注射PTX 5 0mg/kg ,对照组同法等量生理盐水注射 ,另设假手术组。结果　对照组相比 ,PTX组TNF α浓度、NFκBp65含量 (IOD )、巨噬细胞炎性蛋白 -2 (MIP 2 )和细胞间黏附因子 -1(ICAM 1)mRNA表达量 (IOD )、髓过氧化物酶(MPO )活性 (U/g)均明显降低 (均P <0 .0 5 )。再灌注 6hPTX组天门冬氨酸转氨酶 (AST)、丙氨酸转氨酶 (ALT)、乳酸脱氢酶 (LDH )含量 (U/L)和湿重 /干重 (W /D )水平也显著降低 (均P <0 .0 5 )。结论　PTX通过减少TNF α的早期释放 ,抑制NFκB活化 ,从而下调趋化因子、黏附分子表达和减少中性粒细胞浸润 ,从而得以减轻肝脏缺血再灌注损伤。     

七氟醚对心肌缺血/再灌注损伤的临床研究进展

背景 七氟醚的心肌保护作用得到广泛关注,大量基础研究表明七氟醚对心肌缺血/再灌注损伤(myocardial ischemia/reperfusion injury,MI/RI)具有确切的保护作用.然而,临床中关于七氟醚具有心肌保护作用的结论尚未完全统一.目的 通过总结近年的研究进展对七氟醚的心肌保护作用进行阐述.内容 不同心脏手术及非心脏手术中七氟醚药物处理的心肌保护效果.趋向 今后仍需加强对七氟醚心肌保护作用的临床研究,为围手术期患者的心肌保护提供更为可靠的理论依据.     

Effect of trapidil in ischemia/reperfusion injury on rat small intestine.

To investigate the effect of trapidil on the intestinal ischemia-reperfusion injury, we determined malondialdehyde levels as a indicator of lipid peroxidation, nitrite and nitrate levels as reflections of nitric oxide metabolism, and histopathological findings in rats subjected to 40 min of ischemia and 2 h of reperfusion. Histopathological evaluation demonstrated that trapidil treatment has a protective effect on intestinal mucosa and reduces inflammatory cell infiltration in lamina propria, which is consistently noted in the untreated ischemic and reperfused intestines. Possible mechanism of this effect may be explained by the reduced lipid peroxidation (mean malondialdehyde level 3.72 +/- 0.27 vs. 6.13 +/- 0.44, p <.0001) and improved nitric oxide metabolism (mean nitrite plus nitrate 38.21 +/- 2.33 vs. 30.14 +/- 1.47, p =.022).     

Attenuation of ischemia/reperfusion injury by N-acetylcysteine in a rat hind limb model

BACKGROUND: Ischemia/reperfusion is a complex set of events with severe pathologic consequences. Reperfusion initiates both the local and systemic damage in part through rapid oxygen generation. N-acetylcysteine (NAC) is a scavenger of free radical species, inhibits neutrophil accumulation, acts as a vasodilator and also improves microcirculation. In present study, we examined the protective effect of NAC in a rat hind limb ischemia/ reperfusion model. Dimethyl-sulfoxide (DMSO), a well-known antioxidant was also tested for comparison. MATERIALS AND METHODS: Ischemia was induced for 4 h by vascular clamping and followed by 1 h of reperfusion. Muscle injury was evaluated in 3 groups as a saline group (control), DMSO group, and NAC group. Plasma levels of creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS), and blood HCO(3), as well as muscle tissue TBARS, were measured at the end of reperfusion. Muscle tissue samples were taken for histological evaluation. RESULTS: DMSO and NAC group showed significant amelioration of plasma CPK (P < 0.05, P < 0.05), plasma TBARS (P < 0.05, P < 0.05), and muscle tissue TBARS (P < 0.05, P < 0.05) compared with the control group. Similarly, neutrophil infiltration in DMSO and NAC groups were significantly less prominent than the control group (P < 0.01, P < 0.01). CONCLUSIONS: These results show that NAC improved effectively ischemia reperfusion injury in a rat hind limb model.     

Protective effects of propofol against ischemia/reperfusion injury in rat kidneys

Aim: The purpose of this study was to investigate and compare the efficiency of propofol in the reduction of injury induced by free radicals in a rat model of renal ischemia/reperfusion (I/R). Method: Twenty-four Wistar rats were divided into four groups in our study. Rats in the sham group underwent laparotomy and were made to wait for 120 min without ischemia. Rats in the control group were given nothing with ischemia–reperfusion. Rats in the I/R groups were given propofol (25 mg/kg) and 10% intralipid (250 mg/kg) ip, respectively, 15 min before the ischemia for 60 min followed by reperfusion for 60 min. The kidney tissues of the rats were taken under anesthesia at the end of the reperfusion period. Evaluation of biochemical malondialdehyde (MDA), superoxide dismutase, and catalase activities and histopathological analysis were performed with these samples. Results: I/R significantly increased MDA levels (p < 0.05). Histopathological findings of the control group confirmed that there was renal impairment by tubular cell swelling, interstitial edema, medullary congestion, and tubular dilatation. MDA levels were lower in the propofol group compared to control group (p < 0.05). In the propofol group, the level of histopathological scores is significantly decreased than control and intralipid groups in ischemia–reperfusion. Conclusion: Our results demonstrate that I/R injury was significantly reduced in the presence of propofol. The protective effects of propofol may be due to their antioxidant properties. These results may indicate that propofol anesthesia protects against functional, biochemical, and morphological damage better than control in renal I/R injury.     

Protective effects of anti-neutrophil antibody against myocardial ischemia/reperfusion injury in rats

Neutrophil activation initiates myocardial ischemia/reperfusion (I/R) injuries. The aim of this study is to evaluate the in vitro functions of an anti-neutrophil monoclonal antibody, Urge-8, and its therapeutic efficacy against myocardial ischemia (MI) in rats. We measured in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. MI was induced in Wistar rats by clamping the left coronary artery for 1 h. Rats received either isotype-negative control IgG(1) (control group, n = 20), 250 microg/kg of Urge-8 before (pre-treatment group, n = 20) or after (post-treatment group, n = 20) MI. The three groups were compared during the first 24 h after reperfusion with respect to changes in mean arterial pressure, heart rate, body temperature, biochemistry, serum cytokines, myocardial neutrophil infiltration, survival rate, and size of MI. Urge-8 effectively suppressed in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. The Urge-8 treated groups showed higher levels of arterial pressure and survival rate, lower values of interleukin-6 and interleukin-8, lower grade of myocardial neutrophil infiltration, and smaller MI size as compared to the control group. In conclusion, Urge-8 is effective against myocardial I/R injury by suppressing certain functions and myocardial infiltration of neutrophils in rats.     

阿片类药物减轻急性缺血/再灌注损伤及相关机制

背景 缺血预处理对于器官缺血/再灌注损伤（ischemia/reperfusion injury,I/RI）具有强大的保护作用,但其临床应用受到时机以及伦理学的限制.近年来有研究发现阿片类药物预处理以及后处理对组织器官I/RI同样具有保护作用,其既不损伤器官又能产生与缺血预处理相同的效果,是更为可行的治疗措施. 目的 在将阿片类药物处理推广至临床应用前,仍需进行更多大规模的临床研究.拟就阿片类处理减轻I/RI的发展过程及其作用机制进行探讨. 内容 阿片类药物处理I/RI的几种方式及其机制. 趋向 阿片类药物处理比较其他损伤性处理方式更易操作,且对I/RI同样具有保护作用,有望成为日后治疗的热点之一.     

肢体缺血/再灌注损伤诱发大鼠小肠组织自噬的机制研究

目的 观察大鼠肢体缺血/再灌注损伤（limb ischemia/reperfusion injury,LI/RI）对小肠组织自噬的影响. 方法 采用大鼠LI/RI模型,将雄性SD大鼠48只按随机数字表法随机分为两组（每组24只）：假手术组（S组）和缺血/再灌注（ischemia/reperfusion,I/R）组,两组分别再分为再灌注0（T0）、2（T2）、4（T4）、8 h（T8）4个亚组,每亚组6只.I/R组阻断血流3h后再灌注,S组不阻断血流,分别于上述4个时点测定各组血清中乳酸脱氢酶（lactate dehydrogenase,LDH）活性,荧光显微镜下观察小肠细胞自噬小体,聚合酶链式反应（polymerase chain reaction,PCR）检测自噬相关基因Beclin1、Atg5的mRNA表达,蛋白免疫印迹法（Western blot）检测自噬标志蛋白LC3蛋白的表达水平. 结果 I/R组T2、T4、T8时点血清LDH分别为[（4 623±397）、（5046±413）、（4 762±431） U/L]（P〈0.05）,与S组相同时点比较,分别升高约78％、87％、81％;I/R组荧光显微镜下单位面积自噬小体与S组比较明显增加;I/R组T2、T4、T8时点Beclin1表达增加,与S组比较,分别增加约42％、69％、33％（P〈0.05）;I/R组T2、T4、T8时点Atg5表达增加,与S组比较,分别增加约80％、121％、73％（P＜0.01）;I/R组T2、T4、T8时点LC3表达增加,与S组比较,LC3Ⅱ与LC3I的比值分别增加约169％、186％、176％（P＜0.01）. 结论 LI/RI可致大鼠小肠组织自噬水平增加.     

Protective effects of vitamins A and E pretreatment in venous ischemia/reperfusion injury

It has been suggested that venous ischemia is more injurious to tissue viability than is arterial ischemia of equivalent duration. The precise mechanism of tissue damage due to venous ischemia is still not well-determined. Current research has shown that it is multifactorial, and that lipid peroxides, prostanoid metabolism, and a free radical mechanism are the major contributors. Vitamins A and E are lipid-soluble vitamins that have been suggested to be successful in the treatment of arterial ischemia/reperfusion injury due to their antioxidant properties. In the present study, the authors examined the protective effects of vitamins A and E pretreatment on reperfusion injury induced by venous occlusion of rat epigastric island flaps based on an epigastric artery and vein pedicle. In the first part of the study, to determine critical ischemia time, epigastric island skin flaps (3 x 6 cm) were elevated on their vascular pedicles in 40 male Sprague Dawley rats. Total venous occlusion of the skin flap was produced by ligating all draining veins and clamping the epigastric vein. Arterial inflow was left intact. Rats were randomly assigned to five groups (n=8) for 2, 5, 7, 9, and 10 hr of venous ischemia. Despite the occurrence of widespread reperfusion injury, reflow was established (p<0.005) at 9 hr. In the second part of the study, 20 rats were randomly divided into four groups (n=5). The effects of vitamins A and E following 9 hr ischemia/reperfusion injury were examined. Rats were pretreated with vitamin E, vitamin A and vitamins A+E for 5 days. At the end of the fifth day, each rat had undergone an epigastric island skin flap and venous occlusion, as described above. Mean surviving flap area (percent) and plasma lipid peroxides (TBARs), total thiol content (t-SH), glutathione peroxidase (Gpx), and superoxide dismutase (SOD) were determined for each rat. Results suggest that, in the prevention of venous ischemia/reperfusion injury, vitamin A and vitamin E are not effective when used as single agents; however, when used in combination, they significantly increase surviving flap area by a synergistic effect.     

Protective effects of antioxidant medications on limb ischemia reperfusion injury

BACKGROUND: N-acetylcysteine, beta-glucan, and coenzyme Q(10) were shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on ischemia reperfusion injury of limb. MATERIAL AND METHOD: Forty-four New Zealand white rabbits, all female, weighing between 2.3 to 4.2 (mean 3.8) kg, were used in the study. Four study groups were arranged of 11 animals each, by randomization. The first group was the control group (Group C), the other groups were the Group Q, which was medicated with coenzyme Q10, the Group betaG, which was medicated with beta-glucan, and the Group N, medicated with N-acetylcysteine. After baseline measurements, for the ischemia-reperfusion experiments, common iliac artery was clamped and collateral flow was occluded by a rubber arterial tourniquet wrapped around the thigh at the proximal third of the leg. After 60 min of transient ischemic period, the limb was perfused for 180 min. After perfusion, biopsy was taken from the adductor magnus muscle. Second blood sampling was done after reperfusion period. Blood and tissue analysis were done and evaluated statistically. RESULTS: Baseline and post-reperfusion levels of glutathione peroxidase (GPx), super oxide dismutase (SOD), malonyldialdehyde (MDA), and nitric oxide (NO) changed significantly. While MDA levels increased in the control group, it decreased in the other study groups. The increase in GPx and SOD levels were significant in all groups except the control group. Levels of NO were found to have decreased in the control group, whereas it had increased in the other groups. CONCLUSION: Antioxidant medication may help lowering limb ischemia reperfusion injury. All mentioned medications in our study are shown to be able to have an effective role for preventing ischemia reperfusion injury to some extent through their antioxidant properties.     

褪黑素对大鼠肝缺血再灌注损伤的保护作用

目的 观察褪黑素(Mel)对大鼠肝组织caspase-3表达的影响及对肝缺血再灌注损伤的保护作用.方法 将72只Wistar大鼠,随机分为褪黑素处理3、6、12、24 h组(Mel组),同样乙醇溶媒对照组(Alc组)和生理盐水对照组(NS组)也分别按3、6、12、24 h各自分为4组,总共为12组.建立肝缺血再灌注损伤模型,于不同时点测定血清肝组织生化酶:ALT、AKP、对肝组织进行Caspase-3免疫组织化学染色.结果 ALT在再灌注后各时点Mel组均显著低于Alc及NS对照组(P＜0.05),AKP在再灌注后6、12、24 h,Mel组显著低于Alc及NS对照组(P＜0.05),Mel组再灌注后各时点的Caspase-3染色阳性细胞率均显著低于对照组(Alc组和Ns组,P＜0.05),以上各项指标在各时点Alc组与NS组比较差异无统计学意义(P＞0.05).结论 Mel能够减轻大鼠肝缺血再灌注损伤时的肝功能损害,抑制肝细胞Caspase-3的表达,减少肝细胞凋亡,对大鼠肝脏缺血再灌注损伤具有保护作用.     

N-乙酰半胱氨酸预处理对肝脏缺血再灌注损伤的保护作用

目的 探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)预处理对肝脏缺血再灌注损伤的保护作用.方法 18 例肝血管瘤手术患者随机分为3 组(n=6):对照组(C0)、NAC 预处理组(PR)和NAC 后处理组(PO),其中PR和PO 组分别于肝门阻断前和开放后给予NAC 120 mg/kg.三组患者均于切皮前(T0)、肝门阻断开放后1 h(T1)及6 h(T2)抽血检测谷丙转氨酶活性(ALT)和谷草转氨酶(AST)水平,并于肝门阻断开放后1 h(T1)取肝组织测定丙二醛(MDA)含量及核因子κB(NF-κB)活性.结果 肝门阻断开放后1 h(T1)和6 h(T6),各组的ALT 和AST 水平均明显高于肝门阻断前(T0)水平(P<0.01);与对照组相比,PR 和PO 组的MDA 含量在肝门阻断开放后1 h(T1)明显减少(P<0.01),但NF-κB 的活性仅在PR 组显示有明显的降低(P<0.01).结论 NAC 预处理可有效防治肝脏缺血再灌注损伤,其机制与抑制再灌注后NF-κB 的启动激活有关.