人参总皂甙对犬肾自体移植再灌注损伤中钙离子内流？…

目的：为了解人参皂总甙对犬肾移植再灌注中钙离子的内流阻滞作用。方法：采用犬肾移植模型观察再灌注后２４ｈ肾组织细胞中钙离子含量及移植前后不同时期内生肌酐清除值。结果：在肾缺血和再灌注损伤中肾离子含量异常增高。给人参总皂甙后显著减少肾组织细胞中钙离了含量及同时提高内生肌酐清除值。结论：人参总皂地大肾自体移植再灌注损伤中钙离子内流有阻滞作用。减轻肾脏再灌注损伤，保护肾脏功能，并促进肾脏功能早期恢复。     

人参总皂甙对犬肾自体移植再灌注损伤中氧自由基的清除作用

为了解人参总皂甙对肾移植再灌注损伤中氧自由基（ＯＦＲ）的清除作用，采用犬肾移植模型观察再灌注后２４小时肾组织中超氧化物歧化酶（ＳＯＤ）和丙二醛（ＭＤＡ）含量的变化及移植前后不同时期内生肌酐清除值。结果发现，在肾缺血和再灌注损伤过程中肾组织ＳＯＤ活性下降，ＭＤＡ含量异常增高。给人参总皂甙后能显著减少肾组织中ＭＤＡ含量，提高ＳＯＤ活性及内生肌酐清除值。结果提示，人参总皂甙能清除肾脏再灌注损伤产生的ＯＦＲ，保护内源性ＳＯＤ活性，减轻肾脂质过氧化损伤。     

黄芪在犬肾离体灌注保存中的作用

目的研究黄芪提取液对犬肾离体低温灌注及保存中缺血再灌注损伤的影响。方法以常规的HC-A保存液为对照组,以高渗枸橼酸盐嘌呤溶液(HC-A)添加黄芪提取液为实验组,分别对离体犬肾进行低温灌注保存24、48、72 h。通过光镜、电镜观察肾组织结构变化,建立犬肾移植模型,检测移植前后生化指标变化,综合分析。结果实验组保存的犬肾组织超微结构损伤明显轻于对照组。病理组织检查评分,实验组低于对照组(P<0.05)。移植肾早期功能指标检测,移植后2 h实验组血肌酐值(98.25±36.76)μmol/L明显低于对照组(147.26±59.67)μmol/L;移植后24 h血肌酐值(221.55±62.13)μmol/L明显低于对照组(316.12±74.31)μmol/L,而内生肌酐清除值实验组(1.91±0.76)ml·min-1·kg-1明显高于对照组(0.87±0.82)ml·min-1·kg-1,差异均具有显著性(P<0.05)。结论黄芪用于肾脏低温灌注保存中,对缺血再灌注损伤的肾脏有一定保护作用。     

钙离子拮抗剂促移植肾功能早期恢复作用的临床研究

本文报告我院使用钙离子拮抗剂异搏定加入灌注液中对２５例供肾进行灌洗，并在移植肾血流开放的同时由肾动脉注入异搏定稀释液，来减少移植肾的冷缺血及再灌注损伤；结果发现术后第１、４、７天实验组患者血肌酐（Ｃｒ）、血β２－微球蛋白（β２－ＭＧ）、血清过氧化物歧化酶（ＳＯＤ）值均明显鸱地对照组，证明钙离子拮抗剂能减轻移植肾的损伤，促进移植肾功能早期恢复。     

肾脏缺血再灌注损伤及其修复与细胞凋亡的关系研究进展

肾脏缺血再灌注损伤(IRI)及其修复在肾移植中不可避免,它们是影响移植肾早期功能恢复和长期存活的重要因素.近年来研究发现,肾脏IRI及其修复与细胞凋亡密切相关.肾脏缺血再灌注(IR)期间多种与细胞凋亡有关的因素和途径被激活,一方面促进肾脏细胞凋亡,参与肾脏IRI;另一方面则抑制肾脏细胞凋亡,减轻肾脏IRI,参与损伤后修复.本文就肾脏缺血再灌注损伤及其修复与细胞凋亡的关系研究进展做如下综述.     

人参总皂甙抗心肌缺血-再灌注损伤的作用机制

目的 探讨人参总皂甙抗心肌缺血－再灌注损伤作用及其作用机制。方法成年杂种犬１６条随机分为两组,每组８条。对照组：分别于主动脉阻断前１小时和再灌注即刻２次静脉滴注生理盐水各１００ｍｌ;用药组：分别于相同时间２次静脉滴注含人参总皂甙（１２．５ｍｇ／ｋｇ）的生理盐水务１００ｍｌ,通过常温体外循环动物模型,测定血流动力学、细胞内游离钙浓度、心肌细胞线粒体磷脂含量、线粒体钙泵活性和心肌组织化学等,研究人参总皂甙的心肌保护机制。结果 再灌注３０分钟和６０分钟时人参总皂甙能明显改善再灌注期间心脏收缩和舒张功能,两组左心室收缩压、左心室压力变化率比较差异有显著性（Ｐ〈０．０１）,用药组心肌细胞内游离钙浓度明显低于对照组（Ｐ〈０．０１）,线粒体磷脂含量、线粒体钙泵活性高于对照组（Ｐ〈０．０１）,用药组心脏再灌注后心律失常发生率明     

人参总皂甙对高能冲击波肾的保护作用

人参总皂甙对高能冲击波肾的保护作用廖勇彬黄齐旺黄晓生司徒净普徐宝琼人参总皂甙已被用于保护缺血再灌注的心脏和热缺血的肾脏。本研究旨在探讨人参总皂甙对高能冲击波肾的保护作用。材料和方法本组３０例，其中男性１８例，女性１２例，年龄２０～４５岁，平均３２．４...     

应用电子顺磁共振技术研究大鼠肾移植缺血再灌注过程中的NO水平及变化

目的应用电子顺磁共振(EPR)技术动态监测大鼠移植肾缺血再灌注过程中一氧化氮(NO)的产生及其作用. 方法雄性LEW大鼠75只,8～10周龄,体重200～230 g.30只作为供体,供肾0 ℃保存24 h.其余45只分3组,每组15只.第1组为对照组,麻醉后开腹,暴露30 min后关腹;第2组为单纯肾移植组,行同基因肾移植,移植肾再灌注同时切除双肾;第3组为肾移植加N-硝基-L-精氨酸甲脂(L-NAME)组,移植肾再灌注同时切除双肾,供体和受体术前2 h分别给予L-NAME 30 mg/kg.应用EPR动态测定移植肾恢复血流前及之后各时间点NO水平.测定恢复血流后24 h和120 h血肌酐、肾小球滤过率及肾组织羰基含量. 结果单纯肾移植组再灌注后15 min NO开始显著增加并持续上升,120 min达较高水平后迅速下降,到210 min恢复再灌注前水平;肾移植加L-NAME组呈类似变化趋势,但NO水平明显低于前组.L-NAME组的24 h和120 h血肌酐水平均显著高于单纯移植组(P<0.05);24 h(P<0.05)和120 h(P<0.01)肾小球滤过率均显著低于移植组.L-NAME组的24h组织羰基含量显著低于单纯移植组(P<0.05),120 h高于单纯移植组(P<0.05). 结论冷缺血移植肾再灌注过程中,NO早期增加并迅速下降,对移植肾以保护为主.应用L-NAME抑制NO后不利于移植肾功能恢复.     

移植肾缺血再灌注损伤的临床分析

目的 :评价综合防治移植肾缺血再灌注损伤的临床价值。方法 :对本中心开展的 6 0例无特殊情况的同种异体肾移植术应用综合方法防治移植肾缺血再灌注损伤进行分析。结果 :52例恢复良好 ,7例并发急性排斥反应延期恢复 ,1例并发加速排斥反应切除移植肾。结论 :移植肾缺血再灌注损伤经过合理的防治 ,大多预后良好。     

钙拮抗剂在泌尿外科的应用

随着钙拮抗剂(Calciumantagonist,CA)作用机制的深入研究及其种类、剂型的不断研制,CA越来越多地应用于临床,并取得了令人注目的成效。CA在泌尿外科临床上也收到了较好的效果,现对此作一综述。1　CA在肾移植中的应用研究证明,肾移植时再灌注损伤是引起移植肾损伤的主要原因。CA在肾移植中的作用是减少缺血-再灌注损伤,扩张肾血管,促进移植肾肾小球滤过率增加及肾功能早期恢复,减轻免疫抑制剂的肾毒性和减少排斥反应发生,发挥保护肾脏的效应。主要使用方法有:1加入灌注液中。2移植术中开放血流前静脉滴注或肾动脉注入。3移植术后禁食期…     

新霉素对脑缺血再灌注损伤的保护作用

目的：探讨钙及磷酯酶Ｃ（ＰＬＣ）在脑缺血再灌注损伤中的作用机制及ＰＬＣ抑制剂新霉素是否通过抑制ＰＬＣ活性而起脑保护作用。方法：和放血降压法建立大鼠全脑缺血模型，采用原子吸收光谱法及干湿法测定缺血再灌注后脑组织含钙量。含水量变化及新霉素对其影响。结果：再灌组含钙量、含水量较对照组升高（Ｐ〈０．０５）；再灌组内随灌注时间延长，脑组织含钙量、含水量增高（Ｐ〈０．０５）；给药组含钙量、含水量均较再灌组降低     

Renal protection by brief liver ischemia in rats

BACKGROUND: In this study, we evaluated the beneficial effect of brief ischemia and reperfusion, which was shown to have local effects on liver previously, on kidney as a remote organ in rats. METHODS: Male Wistar rats were divided into three groups: group I, sham; group II, renal ischemia for 45 min; and group III, 10 min of brief hepatic ischemia and 10 min of reperfusion after 45 min of renal ischemia. Biochemical determination, tumor necrosis factor (TNF)-alpha and tissue thiobarbituric acid-reactive substances (TBARS) levels, and histopathologic findings were evaluated at 45 min and 24 hr of reperfusion. RESULTS: Although blood urea nitrogen and creatinine levels were similar at 45 min in groups II and III, these levels were lower in group III at 24 hr. Creatine clearance values were higher and fraction excretion of sodium values were lower in group II than in group III at 24 hr. Lactate dehydrogenase levels of groups III and II were similarly elevated at 45 min, whereas group III values decreased more rapidly than those of group II at 24 hr. At 45 min of reperfusion, TNF-alpha and tissue TBARS levels were found lower in group III than in group II. Histopathologic parameters including congestion and tubular vacuolization, tubular cell detachment, and necrosis were significantly reduced in group III as compared with results of group II 45 min after ischemia. All histopathologic parameters were defined as statistically better in group II at 24 hr. CONCLUSIONS: The beneficial effect of brief ischemia of liver on renal ischemia as a remote organ was confirmed by biochemical, histopathologic, and ultrastructural findings.     

The enhancement of cellular cAMP with olprinone protects autotransplanted rat kidney against cold ischemia-reperfusion injury

The administration of a cyclic nucleotide analog improves cold ischemia/reperfusion injury in several organs. The type 3 phosphodiesterase inhibitor olprinone is a potent stimulus that enhances cellular cAMP levels. The present study was performed to investigate the protective effects of enhanced intracellular cAMP levels by olprinone in rat orthotopic kidney transplantation. Autotransplantation and immediate contralateral nephrectomy were performed in Lewis rats after 18 hours of graft storage at 4 degrees C in University of Wisconsin (UW) solution with or without 25 microg/mL olprinone hydrochloride. At 2 hours after reperfusion, serum and urinary biochemical indicators of renal dysfunction and injury were measured: serum creatinine, fractional excretion of Na+ and urinary N-acetyl-D-glucosaminidase. Additionally, intracellular cAMP in kidney tissues was measured by a radioimmunology method. Compared to the only UW solution group, olprinone hydrochloride significantly reduced the increased in serum creatinine, FENa and NAG caused by renal ischemia/reperfusion injury, after 2 hours of reperfusion. The content of cAMP at the endpoint of 18 hours cold preservation was significantly greater in the UW plus olprinone hydrochloride group than that in the UW group. Two hours after reperfusion, the content of cAMP in the UW plus olprinone hydrochloride group was still significantly higher than that in the UW group without containing olprinone hydrochloride. These results support a beneficial effect of olprinone against cold ischemia and reperfusion injury via an increased intracellular cAMP levels.     

一氧化氮与大鼠缺血性急性肾衰竭关系的实验研究

目的 研究一氧化氮（ＮＯ）在缺血性急性肾衰竭病理过程中的作用。方法 通过夹闭大鼠双侧肾蒂４５分钟后再松夹复制出急性肾衰（ＡＲＦ）模型,各组在松夹后分别静滴生理盐水,Ｌ－精氨酸,Ｄ－精氨酸,Ｎ－硝基－Ｌ－精氨酸（ＮＬＡ）。结果 与盐水对照组相比,Ｌ－精氨酸组菊糖清除率和再灌注早期的尿流率增高（Ｐ〈０．０５）,尿钠排泄分数下降（Ｐ〈０．０５）,肾病理损害也较轻（Ｐ〈０．０５）,ＮＬＡ虽升高血压（Ｐ〈０     

A subpopulation of mitochondria prevents cytosolic calcium overload in endothelial cells after cold ischemia/reperfusion.

BACKGROUND: Calcium represents a key mediator of cold ischemia/reperfusion (CIR) injury presumably by affecting mitochondrial function. In this study, we investigated cellular and mitochondrial changes of calcium homeostasis in sublethally damaged human endothelial cells. METHODS: Changes in cellular and mitochondrial calcium concentrations were studied after cold ischemia in University of Wisconsin solution for 12 hr and reperfusion in ringer solution. Cytosolic-free calcium concentration ([Ca2+]c) and mitochondrial-free calcium content ([Ca2+]m) were analyzed by fura-2 and rhod-2 fluorescence, respectively. Pretreatment of cells with ruthenium red (RR) or a H+-ionophore was used to inhibit mitochondrial calcium uptake. Mitochondrial membrane potential (DeltaPsim) was measured by 5,5',6,6'-tetrachloro- 1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide and 3,3'-dihexyloxacarbocyanine iodide fluorescence. RESULTS: Twelve-hr cold ischemia did not induce apoptosis in endothelial cells. In such sublethally damaged cells, [Ca2+]c rose from approximately 20 nmol/L after cold ischemia to approximately 120 nmol/L during reperfusion. Pretreatment with RR leads to an approximately 5-fold rise in [Ca2+]c. Image analysis revealed a significant increase of [Ca2+]m in a subpopulation of mitochondria during reperfusion. This was not the case in RR-pretreated cells. DeltaPsim decreased significantly during cold ischemia and was sustained during reperfusion. The loss of DeltaPsim can be related to a reduced portion of mitochondria exhibiting high DeltaPsim. CONCLUSIONS: Our results suggest that cytosolic calcium influx during CIR is buffered by a selective portion of mitochondria in human umbilical vein endothelial cells. These mitochondria protect cells against cytosolic calcium overload and probably against subsequent cell injury.     

Role of iron in postischemic renal injury in the rat

To determine whether iron participates in free radical-mediated postischemic renal injury and lipid peroxidation, we examined the effects of removal of endogenous iron or provision of exogenous iron following renal ischemia, as well as the effects of renal ischemia and reperfusion on renal venous and urinary "free" iron. Rats underwent 60 minutes of renal ischemia and were studied after either 24 hours (inulin clearance) or 15 minutes (renal malondialdehyde content) of reperfusion. Infusion of the iron chelator deferoxamine (200 mg/kg/hr) during the first 60 minutes of reperfusion resulted in a marked improvement in renal function (inulin clearance: 879 +/- 154 vs. 314 +/- 74 microliter/min; P less than 0.025) and a reduction in lipid peroxidation (renal malondialdehyde: 0.449 +/- 0.06 vs. 0.698 +/- 0.08 mmol/mg prot; P less than 0.05) compared to control animals. Infusion of 50 mg/kg/hr deferoxamine also protected renal function after ischemia (inulin clearance: 624 +/- 116 vs. 285 +/- 90 microliter/min; P less than 0.05) and resulted in less histologic injury. Iron-saturated deferoxamine had no protective effect. Conversely, infusion of the iron complex EDTA-FeCl3 during reperfusion exacerbated postischemic renal dysfunction and lipid peroxidation. Following renal ischemia there was no detectable increase in "free" iron in arterial or renal venous plasma. However, urinary "free" iron increased 10- to 20-fold following reperfusion. Iron chelators which underwent filtration and gained access to this free iron in the urine (free deferoxamine or inulin-conjugated deferoxamine) provided protection, whereas a chelator confined to the vascular space (dextran-conjugated deferoxamine) did not.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protective effect of erythropoietin on renal ischemia and reperfusion injury

BACKGROUND: Multiple protective effects of erythropoietin (EPO), such as antiapoptotic, antioxidant, angiogenic and neuroprotective effects, against ischemia have been demonstrated in cell culture and animal models. Genistein is also a potent tyrosine kinase inhibitor. The aims of the present study were to evaluate the effects of EPO on renal ischemia/reperfusion injury and to determine the role of the tyrosine kinase pathway on this process. METHODS: Sprague-Dawley rats were assigned to five groups: (i) sham (Group I); (ii) control with renal ischemia (right nephrectomy and clamping on the left renal pedicle for 45 min and reperfusion; Group II); (iii) EPO + ischemia (Group III); (iv) genistein (an inhibitor of tyrosine kinase) + ischemia (Group IV); and (v) EPO + genistein + ischemia (Group V). Recombinant human EPO (1000 IU/kg) and genistein (10 mg/kg) were given 2 hours before ischemia. Blood samples and the left kidney were obtained after 45 min of reperfusion from half of the rats and after 24 h from the other half. RESULTS: The blood urea nitrogen, creatinine, tumour necrosis factor-alpha (P < 0.05) and interleukin-2 (P < 0.01) levels, and renal tissue lipid peroxidation (P < 0.05) were significantly lower in Group III than in Group II at 45 min of reperfusion. Following 24 h of reperfusion, EPO decreased tissue peroxidation and histopathological injury, whereas genistein reversed it. The most prominent ischemic injury was observed in Group IV in which genistein was administered. There was no significant difference between Groups II and V. CONCLUSIONS: These results suggest that EPO is effective in attenuating renal ischemia/reperfusion injury, and this effect may be related to tyrosine kinase activity.     

Picroside II decreases the development of fibrosis induced by ischemia/reperfusion injury in rats

In kidney transplantation, renal ischemia and reperfusion injury was one of the leading factors to the development of renal fibrosis, which was the main cause of graft loss. The fibrogenic changes were associated with the long term inflammation elicited by ischemia and reperfusion injury. In the present study, we investigated the role of the Picroside II, the main active constituents of the extract of picrorrhiza scrophulariiflora roots, in attenuating renal fibrosis in a renal ischemia and reperfusion injury model. We induced ischemia and reperfusion injury in kidneys treated with or without Picroside II. We observed that inflammation and tissue fibrosis were increased in ischemia and reperfusion injury group compared to Picroside II group, however, these changes were significantly decreased by the treatment with Picroside II. We concluded that Picroside II can protect the ischemic kidney against renal fibrosis and its mechanism may be through the inhibition of the long term inflammation.     

Ablation of free radical-mediated reperfusion injury for the salvage of kidneys taken from non-heartbeating donors. A quantitative evaluation of the proportion of injury caused by reperfusion following periods of warm, cold, and combined warm and cold ischemia

Postischemic renal failure is a severe problem following cadaveric renal transplantation, especially if the kidney has been harvested from a non-heartbeating donor, and thereby subjected to periods of both warm and cold ischemia. It is well established that a substantial component of postischemic injury is produced by oxygen-derived free radicals generated from xanthine oxidase at reperfusion. However, the clinical potential of free radical ablative therapy is dependent upon the proportion of the total injury caused by this reperfusion mechanism, compared with the proportion resulting from ischemic injury per se. Therefore, we quantitatively evaluated these proportions in porcine kidneys subjected to various periods of warm (renal artery occlusion in situ), cold (harvest, cold preservation, and allotransplantation), and combined warm and cold ischemia. Experiments were paired, one kidney treated with either superoxide dismutase (SOD) or allopurinol for free radical ablation, the contralateral kidney serving as a control. Creatinine clearance (Ccr) was measured separately for each kidney 48 hr after reperfusion. After 1 and 2 hr of warm ischemia, Ccr dropped to 50% and 36% of normal, respectively. This was improved to 110% and 55% when SOD was given into the renal artery at reperfusion. Similarly, after 24 and 48 hr of cold ischemia, kidney function was significantly improved from 30% and 18% to 72% and 47% of normal, respectively, when allopurinol was added to the preservation solution. SOD used at harvest and again at reperfusion was particularly effective following combined warm and cold ischemia, in a situation mimicking the harvest of cadaver kidneys from a non-heartbeating donor. These findings suggest that the ablation of free radical-mediated reperfusion injury may improve posttransplant renal function sufficiently to allow expansion of the cadaveric donor pool to include non-heartbeating donors.     

Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.