亲体移植肾早期细胞代谢变化的微透析临床研究
摘要
引言:
慢性肾功能衰竭是一种进展性疾病,有潜在无法治疗的可能。肾脏异体移植手术已成为可以接受的治疗慢性肾衰的方法。成功的肾移植可以改善患者的生存质量和延长其寿命。但肾移植患者的长期预后,依赖于移植受者对移植物的耐受性。供体的排斥反应是肾移植最为常见的并发症。鉴别早期移植排斥反应的失败将导致不可挽回的损失,并且移植物的损害实际上先于临床和生物化学检查异常发生。目前,没有单项的临床、生化、影像诊断能判断肾移植排斥反应或者从其它肾脏疾病进程中鉴别排斥反应。最近对细胞膜磷脂的分解的现象进行广泛的研究,发现尤其在脑的实验模型中如脑缺血、缺氧、低血糖、癫痫和中枢性损伤等,细胞膜分解更为常见。在肾移植中,移植物的排斥反应也会导致细胞损伤,这种情况下,监测移植物细胞间液的甘油变化尤其有意义。血乳酸水平的测定作为评估组织缺氧的一种方法。血乳酸水平是非特异性氧化损害。在排斥反应期间,可能反映早期移植物的灌注改变。
方法:
此次临床实验中有9例病人被选入研究。在手术结束时,于移植肾上极,皮质层内直视下置一根微透析管,透析管外部连接一个装满生理等渗透析液的微泵。手术最后,放置同样的微透析导管与患者的腹部皮下(作为自身对照),关腹。手术后,每隔一个小时,对采集的透析样本中的葡萄糖、乳酸、丙酮酸、甘油进行实时定量的测定。同时对病人进行常规的监测肾功能变化及临床观察。此次临床实验研究中,不干涉其临床用药。以乳酸浓度2mmol/L以下为正常乳酸浓度,大于2mmol/L为乳酸异常。
结果:
1、血尿素氮从术前的16.73±5.77mmol/l,在术后的两天内快速降到8.68±3.39 mmol/l,与既往比较其P值均小于0.05。并在以后的监测时间里尿素氮维持在6-8 mmol/l的正常水平。
2、血肌酐从术前的984.2±244.79ummol/l,在术后两天内快速降到283.06±102.99 ummol/l,与既往比较其P值均小于0.05。并在以后的监测时间里维持在120-200 ummol/l的水平。
3、移植肾的甘油水平明显低与对照组皮下的甘油(P=0.000)。术后早期,皮下甘油有明显升高,140.73±52.35 umol/L到672.57±194.62umol/L。可持续19个小时左右。在术后的57个小时再次出现一个升高,持续约25个小时后下降。与此同时,肾脏的甘油高峰与皮下甘油第二次吻合,但升高幅度低于皮下。
4、移植肾的甘油在研究中并没有明显成倍的升高,从69.54±19.36 umol/L到318.93±105.94 umol/L。每隔一个小时的移植肾甘油均值比较P值均大于0.05。
5、在研究中,甘油和乳酸有较好的相关性(R=0.487,P=0.000)。随着甘油水平的升高,乳酸也有相应的升高。在所有病人总体正常组乳酸与异常组的比较,正常组甘油平均为86.21±31.65 umol/L,异常组为204.37±77.76 umol/L,P=0.000。差异有统计学意义。
结论:
1.微透析技术是一种可以应用于临床实时监测移植肾早期代谢变化的先进方法。
2.甘油保持在一个较为稳定的正常水平,预示病人预后良好。
3.乳酸浓度的升高对细胞有一定的损害。
Backgrounds:
Chronic renal function failure(CRF)is a progressive and fatal disease.Renal all transplantation has become an accepted means of treating humans with chronic renal failure.When successful,a renal allograft may offer the recipient an improved quality of life and extended lifespan.But the long-term prognosis of a kidney transplantation patient is highly dependent on recipient acceptance of the allograft.Rejection of the donor kidney is a common complication.Failure to identify early graft rejection may result in the irretrievable loss of the organ and damage to the graft may be substantial prior to the onset of clinical and biochemical abnormalities.There is currently no single clinical, biochemical,or diagnostic imaging test to diagnose renal allograft rejection or to differentiate rejection from other disease processes of the allograft.Recently,increased lipolytic activity has mainly been studied by measuring phospholipids extracted from tissue homogenate samples in animal models of ischemia,hypoxia,hypoglycemia and epilepsy. Interstitial glycerol harvested by microdialysis seems to be a marker for monitoring of membrane lipolysis.Graft rejection leads to cell injury after renal transplantation.Under this circumstance,it is important to monitor the changes of glycerin in intercellular fluid of graft.The.level of blood lactate may be useful for evaluating anoxic tissue and reflect non-specificity oxidative lesion.During the reject reaction,lactate may reflect early changes of graft.
Methods:
There are nine patients in this clinical experiment.Before the operation is over,we put amicrodialysis catheter upper pole and in lamina cortex of the graft.External part of microdialysis catheter link to a minipump with fulling load of iso-osmia dialysate.At the same time,we put the same microdialysis catheter in abdominal subcutance,consecutive serial samples are collected at 1-hintervals after the operation,glucose, lactate,pyruvate and glycerol concentrations are measured.At the same time,patients do some routine examination and are observed continually. In this clinical empirical study,clinical medications are let alone. Lactate concentration below 2mmol/L is normal and exceeding 2mmol/L is abnormal.
Results:
Urea nitrogen post-operative quickly decrease from 16.73±5.77 mmol/l to 8.68±3.39mmol/l(p＜0.05).Urea nitrogen maintain 6-8mmol/l of normal level.
Carnine post-operative quickly decrease from 984.2±244.?9ummol/l to 283.06±102.99ummol/l(P＜0.05).Carnine maintain 120-200ummol/l of normal level.
The glycerin in graft obviously is lower than in subcutance(P=0.000). Nonage of post-operative,the glycerin in subcutance obviously increase from 140.73±52.35umol/L to 672.57±194.62umol/L and maintain 19 hours. At 57~(th)hours,the glycerin in subcutance emergence thesecond time heightening.At thesame time,the glycerin in graft heighten.
The glycerin in graft do not duplicatly heightened after operation. The range is from 69.54±19.36umol/L to 318.93±105.94umol/L ummol/l. The glycerin of every other one hour comparation is not statistical significance(P＞0.05)
In our study,lactate and glycerin of the graft have better correlation (R=0.289,P=0.000).All patients including normal group(86.21±31.65) umol/L and abnormal group(204.37±77.76)umol/L,glycerin of the graft in abnormal obviously exceed normal group(P=0.000).
Conclusion:
Microdialysis method allows continuous bedside monitoring the changes of metabolism in the graft.
After renal transplantation of relatives in vivo,the glycerin in graft maintains stable level and has no dupilicatily increasing.
With the increasing of lactate,the glycerin in graft also increases. It is damage for the increasing concentration of lactate.
慢性肾功能衰竭是一种进展性疾病,有潜在无法治疗的可能。肾脏异体移植手术已成为可以接受的治疗慢性肾衰的方法。成功的肾移植可以改善患者的生存质量和延长其寿命。但肾移植患者的长期预后,依赖于移植受者对移植物的耐受性。供体的排斥反应是肾移植最为常见的并发症。鉴别早期移植排斥反应的失败将导致不可挽回的损失,并且移植物的损害实际上先于临床和生物化学检查异常发生。目前,没有单项的临床、生化、影像诊断能判断肾移植排斥反应或者从其它肾脏疾病进程中鉴别排斥反应。最近对细胞膜磷脂的分解的现象进行广泛的研究,发现尤其在脑的实验模型中如脑缺血、缺氧、低血糖、癫痫和中枢性损伤等,细胞膜分解更为常见。在肾移植中,移植物的排斥反应也会导致细胞损伤,这种情况下,监测移植物细胞间液的甘油变化尤其有意义。血乳酸水平的测定作为评估组织缺氧的一种方法。血乳酸水平是非特异性氧化损害。在排斥反应期间,可能反映早期移植物的灌注改变。
方法:
此次临床实验中有9例病人被选入研究。在手术结束时,于移植肾上极,皮质层内直视下置一根微透析管,透析管外部连接一个装满生理等渗透析液的微泵。手术最后,放置同样的微透析导管与患者的腹部皮下(作为自身对照),关腹。手术后,每隔一个小时,对采集的透析样本中的葡萄糖、乳酸、丙酮酸、甘油进行实时定量的测定。同时对病人进行常规的监测肾功能变化及临床观察。此次临床实验研究中,不干涉其临床用药。以乳酸浓度2mmol/L以下为正常乳酸浓度,大于2mmol/L为乳酸异常。
结果:
1、血尿素氮从术前的16.73±5.77mmol/l,在术后的两天内快速降到8.68±3.39 mmol/l,与既往比较其P值均小于0.05。并在以后的监测时间里尿素氮维持在6-8 mmol/l的正常水平。
2、血肌酐从术前的984.2±244.79ummol/l,在术后两天内快速降到283.06±102.99 ummol/l,与既往比较其P值均小于0.05。并在以后的监测时间里维持在120-200 ummol/l的水平。
3、移植肾的甘油水平明显低与对照组皮下的甘油(P=0.000)。术后早期,皮下甘油有明显升高,140.73±52.35 umol/L到672.57±194.62umol/L。可持续19个小时左右。在术后的57个小时再次出现一个升高,持续约25个小时后下降。与此同时,肾脏的甘油高峰与皮下甘油第二次吻合,但升高幅度低于皮下。
4、移植肾的甘油在研究中并没有明显成倍的升高,从69.54±19.36 umol/L到318.93±105.94 umol/L。每隔一个小时的移植肾甘油均值比较P值均大于0.05。
5、在研究中,甘油和乳酸有较好的相关性(R=0.487,P=0.000)。随着甘油水平的升高,乳酸也有相应的升高。在所有病人总体正常组乳酸与异常组的比较,正常组甘油平均为86.21±31.65 umol/L,异常组为204.37±77.76 umol/L,P=0.000。差异有统计学意义。
结论:
1.微透析技术是一种可以应用于临床实时监测移植肾早期代谢变化的先进方法。
2.甘油保持在一个较为稳定的正常水平,预示病人预后良好。
3.乳酸浓度的升高对细胞有一定的损害。
Backgrounds:
Chronic renal function failure(CRF)is a progressive and fatal disease.Renal all transplantation has become an accepted means of treating humans with chronic renal failure.When successful,a renal allograft may offer the recipient an improved quality of life and extended lifespan.But the long-term prognosis of a kidney transplantation patient is highly dependent on recipient acceptance of the allograft.Rejection of the donor kidney is a common complication.Failure to identify early graft rejection may result in the irretrievable loss of the organ and damage to the graft may be substantial prior to the onset of clinical and biochemical abnormalities.There is currently no single clinical, biochemical,or diagnostic imaging test to diagnose renal allograft rejection or to differentiate rejection from other disease processes of the allograft.Recently,increased lipolytic activity has mainly been studied by measuring phospholipids extracted from tissue homogenate samples in animal models of ischemia,hypoxia,hypoglycemia and epilepsy. Interstitial glycerol harvested by microdialysis seems to be a marker for monitoring of membrane lipolysis.Graft rejection leads to cell injury after renal transplantation.Under this circumstance,it is important to monitor the changes of glycerin in intercellular fluid of graft.The.level of blood lactate may be useful for evaluating anoxic tissue and reflect non-specificity oxidative lesion.During the reject reaction,lactate may reflect early changes of graft.
Methods:
There are nine patients in this clinical experiment.Before the operation is over,we put amicrodialysis catheter upper pole and in lamina cortex of the graft.External part of microdialysis catheter link to a minipump with fulling load of iso-osmia dialysate.At the same time,we put the same microdialysis catheter in abdominal subcutance,consecutive serial samples are collected at 1-hintervals after the operation,glucose, lactate,pyruvate and glycerol concentrations are measured.At the same time,patients do some routine examination and are observed continually. In this clinical empirical study,clinical medications are let alone. Lactate concentration below 2mmol/L is normal and exceeding 2mmol/L is abnormal.
Results:
Urea nitrogen post-operative quickly decrease from 16.73±5.77 mmol/l to 8.68±3.39mmol/l(p＜0.05).Urea nitrogen maintain 6-8mmol/l of normal level.
Carnine post-operative quickly decrease from 984.2±244.?9ummol/l to 283.06±102.99ummol/l(P＜0.05).Carnine maintain 120-200ummol/l of normal level.
The glycerin in graft obviously is lower than in subcutance(P=0.000). Nonage of post-operative,the glycerin in subcutance obviously increase from 140.73±52.35umol/L to 672.57±194.62umol/L and maintain 19 hours. At 57~(th)hours,the glycerin in subcutance emergence thesecond time heightening.At thesame time,the glycerin in graft heighten.
The glycerin in graft do not duplicatly heightened after operation. The range is from 69.54±19.36umol/L to 318.93±105.94umol/L ummol/l. The glycerin of every other one hour comparation is not statistical significance(P＞0.05)
In our study,lactate and glycerin of the graft have better correlation (R=0.289,P=0.000).All patients including normal group(86.21±31.65) umol/L and abnormal group(204.37±77.76)umol/L,glycerin of the graft in abnormal obviously exceed normal group(P=0.000).
Conclusion:
Microdialysis method allows continuous bedside monitoring the changes of metabolism in the graft.
After renal transplantation of relatives in vivo,the glycerin in graft maintains stable level and has no dupilicatily increasing.
With the increasing of lactate,the glycerin in graft also increases. It is damage for the increasing concentration of lactate.
引文
1. Mathews KG, Gregory CR , et al. Renal transplants in cats: 66 cases (1987-1996). (J) Am Vet Med Assoc 1997; 211: 1432-1436
2. Racusen LC , Solez K, et al. The banff 97 working classification of renal allograft pathology. (J) Kidney Int 1999; 55:713-723
3. Shaikewitz ST, Chan L. Chronic renal transplant rejection (J) Am J Kidney Dis 1994; 23:884-893
4 . Danovitch GM. Choice of immunosuppressive drugs and individualization of immunosuppressive therapy for kidney transplant patients. (J) Transplant Proc 1999; 31: 2s-6s
5. Brown ED, Chen MYM, et al. Complications of renal transplantation: evaluation with US and radionuclide imaging. (J) radiographics 2000; 20:607-622
6. Farooqui AA, Horrocks LA. Excitotoxicity and neurological disorders: involvement of membrane phospholipids. (J) Int Rev Nerobiol 1994; 36: 267-323
7. Luft FC. Lactic acidosis updates for critical care clinicians. (J) J Am Soc Nephrol 2001; 12: 15-19
8. Amner P, Bolinder J. Microdialysis of adipose tissue ( J ) intern Med 1991; 230: 381-6
9. Bolinder J, Ungerstedt U, Arner P. Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients (J) Disbetologiaa 1992;35:1177-80
10. Tossman U, Ungerstedt U. Microdialysis in the study of extracellular levels of amino acids in the rat brain. (J) Acta Pbysiol Scand 1986; 128: 9-14.
11. K. JANSSON, M. JANSSON, Normal values and differences between intraperitoneal and subcutaneous microdialysis in patients after no complicated gastrointestinal surgery. (J) Scand J Clin Lab Invest 2005; 65: 273-282
12. Hillered L, Person L, Neurochemical monitoring of the acutely injured human brain. (J) Scand J Clin Lab Invest Suppl 1999;229:9-18
13. Sijpkens YW,Doxiadis II ,Mallat MJ ,et al. Early Versus late acute rejection episodes in renal transplantation. (J) Transplantation ,2003 ,75(2) : 204-208
14. Lynch DR, Dawson TM, Secondary mechanisms in neuronal trauma. (J) Curr Opin Neurol,1994,7:510-516
15. Rabkin JM, Orloff SL, Corless cl ,benner KG, Flora KD, Rosen HR et al .Hepatic allograft abscess with hepatic arterial thrombosis .Am (J) Surg 1998; 175:354-9
16. Nilsson OG, Brandt L, Ungerstedt U, Saveland H. Bedside detection of brain ischemia using. intracerebral microdialysis :subarachnoid hemorrhage and delayed and delayed ischemic deterioration. (J) Neurosurgery 1999; 45:1176-84
17. Rojdmark j, Heden P, Ungerstedt U. Prediction of border necrosis in skin flaps of pigs with microdialysis (J) Reconstr Microsurg 2000; 16:129-34
18. Marubayashi S, Takenaka M, Dohi K, Ezaki H, Kawasaki t. Adenine nucleotide metabolism during hepatic ischemia and subsequent blood reflow periods and its relation to organ biability. (J) Transplantation 1980; 30:294-6
19. Lanir A, jenkins RL, Caldwell C, Lee RG, Khettry U, Clouse ME, Hepatic transplantation survival: correlation with adenine nucleotide level in donor liver. (J) Hepatology 1988; 8:471-5
20. Tobias B, Splanchnic metabolism during gut ischemia and short-term endotoxin and hemorrhagic shock as evaluated by intranasal microdialysis (J) Shock 2004,21 (6):572-578
21. Frykholm P, Hillered L, Langstrom B, Persson L, Valtysson J, Watanabe Y, Enblad P: Increase of interstitial glycerol reflects the degree of ischemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion reperfusion primate model. (J) Neural Neurosurgery Psychiatry 71:455-461, 2001.
22. Backstrom T, Goiny M, Cardiac outflow of amino acids and purines during myocardial ischemia and reperfusion. (J) Appl Phys 94:1122-1128,2003
23. Nowak G, Ungerstedt J, Wernerman J, Ungerstedt U, Ericzon BG: Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig model. Liver Transpl 8:424-432,2002.
24. Deitch EA VJ-L, Windsor A. Sepsis and multiple organ dysfunctions. 2002.
25．王毅 近10年美国肾移植病人生存率增高中国医学论坛报/2001年/08月/16日/第021版/
26. Moss A, Najarian JS, Sutherland et al. 5000 kidney transplants-A singlecenter experience. In: Clinical Transplants 2000. Los Angeles: UCLA ImmunogeneticsCenter, 2001:159 -171.
27 . RatnerLE,Ciseck LJ,Moore RG et al. Laparoscopic live donor ne-phrectomy. (J) Transplantation,1995,60(9):1047.
28.Sasaki TM,Finelli F,Bugarin E,et al.Is laparoscopic donor ne-phrectomy the new criterion standeard(J)Arch Surg,2000,135:943-947.
29.Wolf JS,Moon TD,Nakada.Hand assisted Laparoscopic nephrecto-my:technical considerations.(J)TechUro,1 1997,3:123.
30.洪良庆,吴家清,蔡育彬,等.中国医师杂志,2003年增刊.
31.潘光辉,陈正,廖德怀,等.活体亲属供肾肾移植的临床分析。Journal of Modern Clinical Medical Bioengineering,2003,Vo.l9:No.3.
32.Robert Mendez,Thomas Gonwa,for the Prograf StudyGroupA Prospective,Randomized Trial of Tacrolimus in Com-bination with Sirolimus or Mycophenolate Mofetil in Kidney Trans-plantation:Results at 1 Year Transplantation o Volume 80,2005,Number 3:Augustl 5.
33.Ahmed F,Hamdy,Amgad E,et al Ghoneim Comparison of Sirolimus with Low-Dose Tacrolimus V ersus Sirolimus-based Calcineurin In-hibitor-Free Regimen in Live DonorRenalTransplantation American Journal of Transplantation,2005,5:2531-2538.
34.TanHP,KaczorowskiD,BasuA,et al.Tacrolimus Monotherapy After Pretransplantation Thymoglobulin or Campath and Laparoscopy in Living Donor Renal Transplantation Transplantation Proceedings,2005,37:4235-4240.
35.Knight RJ,Burrows L,Bodian C.The influence of acute rejection on long-term renal allograft survival:a comparison of living and cadaveric donor transplantation.Transplantation,2001,72:69-76.
36.Leivestad T,Reisaeter AV,Brekke IB,et al.The role of HLA matching in renal transplantation:experience from one center.Rev Immunogenet,1999,1:343-350.
37.Mitchell L,Halperin D,Anthony L,et al.Lactic acidosis-emphasis on the carbon precursors and buffering of the acid load.[J]Am J Med Sci,1985,289(4):154-159.
38.Balaban RS.Regulation of oxidative phosphorylation in the mammalian cell.Am.physio11990;258:C377-89.
39.Gutierrez G.Cellular energy metabolism during hypoxia.Crit Care Med 1991;19.619-26.
40.Nunn JF.Oxygen.In:Nunn JF,Nunn's applied respiratory,physiology.Oxford:Butterworth-Heinmann Ltd,1993:247-305
41.Staepoole PW,Wright EC;Natural history and course of acqired lactic acidosis in adults, DCA-lactic acidosis study group.Am J Med 1994(94):47-54
42.Ariza M,Gothard JW,Blood lactate and mixed venous arterial PCO2 gradient as indices of poor peripheral perfusion following cardiopulmonary bypass.Intensive Care Med.1991,17:320-324
43.Shangraw RE,Winter.R,Amelioration of lactic acidosis with dichloroacetate during liver transplantion in humans.Anesthesiology 1991;81:1127-1138
44.Cohen RD,Woods HF.Clinical and biochemical aspects of lactic acidosis.Boston:Blackwell Scientific Publications,1976
45.王静,乳酸在运动性中枢疲劳中的作用及机制研究 2005年 博士毕业论文 军事医学科学院卫生学环境医学研究所
46.陈晓红,边联防,姜寿峰等.丹参注射液抗乳酸神经毒性作用及其机制研究.中国药理学通报,2003,19(2):214-6.
47.Norenberg.MD,Mozes LW,et al.Effect of lactic acid on astrocytes in primary culture(J)NeuroPathol,1987,46(2):154-66.
48.Kimelberg HK,Current concept of brain edema:review of Laboratory investigations。(J)Neurosurg,1995,83:1051-1059.
49.Mori S,Morishima S,et al.Impaired activity of volume-sensitive anion channel during lactacidosis-induced swelling In neuronally differentiated NG108-15 cells。(J)Brain Res 2002,957(1):1-11
50.Kempski O,Staub F,Molecular mechanism ofglial cell swelling in acidosis。Adv Neuro,1990,52:39-45
51.Ames A,Nesbett FB.Pathophysiology of ischemic cell death:Ⅱ Changes in plasma membrane permeability and cell volume.(J)Stroke,1983,14:227-233
52.Kempski O,Wroblewska B,Effects of forskolin on growth and morphology of cultured glial and cerebrovascular endothelial and smooth muscle cells.(J)Nt J Dev Neurosci 1987,5:435-445.
53.Ringel F,Chang RC,et al.Contribution of anion transporters to the acidosis-induced swelling and intracellular acidification ofglial cells.(J)Neutochem,2000,75(1):125-132.
54.Hillered L,Ernster L,Influence of in vitro lactic acidosis and hypercapnia on respiratory activity of isolated rat brain mitochondria.Cerebra Blood Flow Metab,1984,4(3):430-437.
55.Nedergaard M.Intracelluar Ca~(2+)transients evoked by lactic acid in cultured mammalian neurons.(J)Am J Physiol,1995,268(2pt2):R506-513.
56.张均田主编.现代药理实验方法上册.北京医科大学,北京协和医科大学联合出版社,1998,第一版,611-619
57.陈立华,杨于嘉,曹美鸿.神经元细胞内钙离子的生理与测定方法,国外医学神经病学神经外科学分册,1996,23(2):60-63.
58.Zhao P,Huang YL,Cheng JS.Taurine antagonizes calcium overload induced by glutamate or chemical hypoxia in cultured rat hippocampal neurons.Neurosci Lett,1999,268(1):25-28.
59.Immke DC,Mecleskey EW.Protons open acid-sensing ion channels by catalyzing relief of Ca~(2+)blockade.Neuron,2003,37(1):75-84.
1.Mitchell L,Halperin D,et al.Lactic acidosis emphasis on the carbon precursors and buffering of the acid load(J).Am J Med Sci,1985,289(4):154-159
2.Kentish J,Aenderson K,Effect of PH on force and stiffness in skinned muscle from rat and guinea-pig ventricle and from rabbit psoas muscle(J)J Physiol Lond,1989,410:679
3.刘昭强,史清钊等,不同浓度乳酸对家兔离体心室肌收缩力和细胞动作电位的影响(J)体育科学,2005,25(7):35-38
4.李春盛,顾伟等 充血性心力衰竭患者循环内皮细胞、血乳酸和一氧化氮浓度的变化(J)中华急诊医学杂志,2005,14(4):313-315
5.Pacold I,Ackerman L,et al.The effects of acute hypertriglyceridemia and high levels of free fatty acids on left ventricular function(J).Am Heart J,1985,110(4):836-840
6.陈炬,李少华等,TMLR对缺血心肌乳酸代谢及线粒体的影响(J)中国病理生理杂志,2004,20(12):2219-2222
7.Javier A,Wendy K,et al.The use and clinical importance of a Substrate Specific Electrode for rapid determination of blood lactate concentrations(J)JAMA,1995,14(3):221
8.Pellerin L,Halestrap AP,et al,Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain(J)Neurosci Res,2005,79:55-64
9.Goldman SA,Pulsinelli WA,et al.The effects of extracelluar acidosis on neurons and glia in vitro.(J)Cereb Blood Flow Metab,1989,9(4):471
10.杜敏逸,周源等,利多卡因对乳酸损害脑细胞的保护作用(J)中华麻醉学杂志,1995,15(9).406-408
11.赵玉武,丁素菊等,硫酸镁对大鼠脑缺血及再灌注时细胞外液谷氨酸、葡萄糖和乳酸的影响,(J)第二军医大学学报,2004,25(10):1108-1110
12.Cater HL,Benham CD,et al,Neuroprotective role of monocarboxylate transport during glucose deprivation in slice cultures of rat hippocampus(J)J Physiol,2001,531(2):459
13.Sakurai T,Yang B,et al.Synaptic adaptation to repeated hypoglycemia depends.on the utilizationg of monocarboxylates in guinea pig hippocampal slices(J).Diabetes,2002,51:430
14.Bliss TM,Cheng E,et al.Dual-gene,dual-cell type therapy against an excitotoxic insult by bolstering neuroener-getics(J).J Neurosci,2004,24(27):6202
15.王静,刘洪涛等,运动性中枢疲劳及乳酸对大鼠大脑皮质神经细胞MCT mRNA表达的影响,(J)中国运动医学杂志,2007,26(1):52-55
16.Krista B,Halling,et al.Evaluation of oxidative stress markers for the early diagnosis of allograft rejiection in feline renal allotransplant recipients with normal renal function(J)Can Vet J.2004,45(10):831
17.Racusen LC,Solez K,et al.The Banff 97 working classification of renal allograft pathology.(J)Kidney Int 1999,55:713-723
18.张立,金亦辉等,在无血清培养基中代谢副产物对杂交瘤细胞生长代谢的影响,乳酸的作用。(J)华东理工大学学报,2001,28(2):157-160
2. Racusen LC , Solez K, et al. The banff 97 working classification of renal allograft pathology. (J) Kidney Int 1999; 55:713-723
3. Shaikewitz ST, Chan L. Chronic renal transplant rejection (J) Am J Kidney Dis 1994; 23:884-893
4 . Danovitch GM. Choice of immunosuppressive drugs and individualization of immunosuppressive therapy for kidney transplant patients. (J) Transplant Proc 1999; 31: 2s-6s
5. Brown ED, Chen MYM, et al. Complications of renal transplantation: evaluation with US and radionuclide imaging. (J) radiographics 2000; 20:607-622
6. Farooqui AA, Horrocks LA. Excitotoxicity and neurological disorders: involvement of membrane phospholipids. (J) Int Rev Nerobiol 1994; 36: 267-323
7. Luft FC. Lactic acidosis updates for critical care clinicians. (J) J Am Soc Nephrol 2001; 12: 15-19
8. Amner P, Bolinder J. Microdialysis of adipose tissue ( J ) intern Med 1991; 230: 381-6
9. Bolinder J, Ungerstedt U, Arner P. Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients (J) Disbetologiaa 1992;35:1177-80
10. Tossman U, Ungerstedt U. Microdialysis in the study of extracellular levels of amino acids in the rat brain. (J) Acta Pbysiol Scand 1986; 128: 9-14.
11. K. JANSSON, M. JANSSON, Normal values and differences between intraperitoneal and subcutaneous microdialysis in patients after no complicated gastrointestinal surgery. (J) Scand J Clin Lab Invest 2005; 65: 273-282
12. Hillered L, Person L, Neurochemical monitoring of the acutely injured human brain. (J) Scand J Clin Lab Invest Suppl 1999;229:9-18
13. Sijpkens YW,Doxiadis II ,Mallat MJ ,et al. Early Versus late acute rejection episodes in renal transplantation. (J) Transplantation ,2003 ,75(2) : 204-208
14. Lynch DR, Dawson TM, Secondary mechanisms in neuronal trauma. (J) Curr Opin Neurol,1994,7:510-516
15. Rabkin JM, Orloff SL, Corless cl ,benner KG, Flora KD, Rosen HR et al .Hepatic allograft abscess with hepatic arterial thrombosis .Am (J) Surg 1998; 175:354-9
16. Nilsson OG, Brandt L, Ungerstedt U, Saveland H. Bedside detection of brain ischemia using. intracerebral microdialysis :subarachnoid hemorrhage and delayed and delayed ischemic deterioration. (J) Neurosurgery 1999; 45:1176-84
17. Rojdmark j, Heden P, Ungerstedt U. Prediction of border necrosis in skin flaps of pigs with microdialysis (J) Reconstr Microsurg 2000; 16:129-34
18. Marubayashi S, Takenaka M, Dohi K, Ezaki H, Kawasaki t. Adenine nucleotide metabolism during hepatic ischemia and subsequent blood reflow periods and its relation to organ biability. (J) Transplantation 1980; 30:294-6
19. Lanir A, jenkins RL, Caldwell C, Lee RG, Khettry U, Clouse ME, Hepatic transplantation survival: correlation with adenine nucleotide level in donor liver. (J) Hepatology 1988; 8:471-5
20. Tobias B, Splanchnic metabolism during gut ischemia and short-term endotoxin and hemorrhagic shock as evaluated by intranasal microdialysis (J) Shock 2004,21 (6):572-578
21. Frykholm P, Hillered L, Langstrom B, Persson L, Valtysson J, Watanabe Y, Enblad P: Increase of interstitial glycerol reflects the degree of ischemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion reperfusion primate model. (J) Neural Neurosurgery Psychiatry 71:455-461, 2001.
22. Backstrom T, Goiny M, Cardiac outflow of amino acids and purines during myocardial ischemia and reperfusion. (J) Appl Phys 94:1122-1128,2003
23. Nowak G, Ungerstedt J, Wernerman J, Ungerstedt U, Ericzon BG: Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig model. Liver Transpl 8:424-432,2002.
24. Deitch EA VJ-L, Windsor A. Sepsis and multiple organ dysfunctions. 2002.
25．王毅 近10年美国肾移植病人生存率增高中国医学论坛报/2001年/08月/16日/第021版/
26. Moss A, Najarian JS, Sutherland et al. 5000 kidney transplants-A singlecenter experience. In: Clinical Transplants 2000. Los Angeles: UCLA ImmunogeneticsCenter, 2001:159 -171.
27 . RatnerLE,Ciseck LJ,Moore RG et al. Laparoscopic live donor ne-phrectomy. (J) Transplantation,1995,60(9):1047.
28.Sasaki TM,Finelli F,Bugarin E,et al.Is laparoscopic donor ne-phrectomy the new criterion standeard(J)Arch Surg,2000,135:943-947.
29.Wolf JS,Moon TD,Nakada.Hand assisted Laparoscopic nephrecto-my:technical considerations.(J)TechUro,1 1997,3:123.
30.洪良庆,吴家清,蔡育彬,等.中国医师杂志,2003年增刊.
31.潘光辉,陈正,廖德怀,等.活体亲属供肾肾移植的临床分析。Journal of Modern Clinical Medical Bioengineering,2003,Vo.l9:No.3.
32.Robert Mendez,Thomas Gonwa,for the Prograf StudyGroupA Prospective,Randomized Trial of Tacrolimus in Com-bination with Sirolimus or Mycophenolate Mofetil in Kidney Trans-plantation:Results at 1 Year Transplantation o Volume 80,2005,Number 3:Augustl 5.
33.Ahmed F,Hamdy,Amgad E,et al Ghoneim Comparison of Sirolimus with Low-Dose Tacrolimus V ersus Sirolimus-based Calcineurin In-hibitor-Free Regimen in Live DonorRenalTransplantation American Journal of Transplantation,2005,5:2531-2538.
34.TanHP,KaczorowskiD,BasuA,et al.Tacrolimus Monotherapy After Pretransplantation Thymoglobulin or Campath and Laparoscopy in Living Donor Renal Transplantation Transplantation Proceedings,2005,37:4235-4240.
35.Knight RJ,Burrows L,Bodian C.The influence of acute rejection on long-term renal allograft survival:a comparison of living and cadaveric donor transplantation.Transplantation,2001,72:69-76.
36.Leivestad T,Reisaeter AV,Brekke IB,et al.The role of HLA matching in renal transplantation:experience from one center.Rev Immunogenet,1999,1:343-350.
37.Mitchell L,Halperin D,Anthony L,et al.Lactic acidosis-emphasis on the carbon precursors and buffering of the acid load.[J]Am J Med Sci,1985,289(4):154-159.
38.Balaban RS.Regulation of oxidative phosphorylation in the mammalian cell.Am.physio11990;258:C377-89.
39.Gutierrez G.Cellular energy metabolism during hypoxia.Crit Care Med 1991;19.619-26.
40.Nunn JF.Oxygen.In:Nunn JF,Nunn's applied respiratory,physiology.Oxford:Butterworth-Heinmann Ltd,1993:247-305
41.Staepoole PW,Wright EC;Natural history and course of acqired lactic acidosis in adults, DCA-lactic acidosis study group.Am J Med 1994(94):47-54
42.Ariza M,Gothard JW,Blood lactate and mixed venous arterial PCO2 gradient as indices of poor peripheral perfusion following cardiopulmonary bypass.Intensive Care Med.1991,17:320-324
43.Shangraw RE,Winter.R,Amelioration of lactic acidosis with dichloroacetate during liver transplantion in humans.Anesthesiology 1991;81:1127-1138
44.Cohen RD,Woods HF.Clinical and biochemical aspects of lactic acidosis.Boston:Blackwell Scientific Publications,1976
45.王静,乳酸在运动性中枢疲劳中的作用及机制研究 2005年 博士毕业论文 军事医学科学院卫生学环境医学研究所
46.陈晓红,边联防,姜寿峰等.丹参注射液抗乳酸神经毒性作用及其机制研究.中国药理学通报,2003,19(2):214-6.
47.Norenberg.MD,Mozes LW,et al.Effect of lactic acid on astrocytes in primary culture(J)NeuroPathol,1987,46(2):154-66.
48.Kimelberg HK,Current concept of brain edema:review of Laboratory investigations。(J)Neurosurg,1995,83:1051-1059.
49.Mori S,Morishima S,et al.Impaired activity of volume-sensitive anion channel during lactacidosis-induced swelling In neuronally differentiated NG108-15 cells。(J)Brain Res 2002,957(1):1-11
50.Kempski O,Staub F,Molecular mechanism ofglial cell swelling in acidosis。Adv Neuro,1990,52:39-45
51.Ames A,Nesbett FB.Pathophysiology of ischemic cell death:Ⅱ Changes in plasma membrane permeability and cell volume.(J)Stroke,1983,14:227-233
52.Kempski O,Wroblewska B,Effects of forskolin on growth and morphology of cultured glial and cerebrovascular endothelial and smooth muscle cells.(J)Nt J Dev Neurosci 1987,5:435-445.
53.Ringel F,Chang RC,et al.Contribution of anion transporters to the acidosis-induced swelling and intracellular acidification ofglial cells.(J)Neutochem,2000,75(1):125-132.
54.Hillered L,Ernster L,Influence of in vitro lactic acidosis and hypercapnia on respiratory activity of isolated rat brain mitochondria.Cerebra Blood Flow Metab,1984,4(3):430-437.
55.Nedergaard M.Intracelluar Ca~(2+)transients evoked by lactic acid in cultured mammalian neurons.(J)Am J Physiol,1995,268(2pt2):R506-513.
56.张均田主编.现代药理实验方法上册.北京医科大学,北京协和医科大学联合出版社,1998,第一版,611-619
57.陈立华,杨于嘉,曹美鸿.神经元细胞内钙离子的生理与测定方法,国外医学神经病学神经外科学分册,1996,23(2):60-63.
58.Zhao P,Huang YL,Cheng JS.Taurine antagonizes calcium overload induced by glutamate or chemical hypoxia in cultured rat hippocampal neurons.Neurosci Lett,1999,268(1):25-28.
59.Immke DC,Mecleskey EW.Protons open acid-sensing ion channels by catalyzing relief of Ca~(2+)blockade.Neuron,2003,37(1):75-84.
1.Mitchell L,Halperin D,et al.Lactic acidosis emphasis on the carbon precursors and buffering of the acid load(J).Am J Med Sci,1985,289(4):154-159
2.Kentish J,Aenderson K,Effect of PH on force and stiffness in skinned muscle from rat and guinea-pig ventricle and from rabbit psoas muscle(J)J Physiol Lond,1989,410:679
3.刘昭强,史清钊等,不同浓度乳酸对家兔离体心室肌收缩力和细胞动作电位的影响(J)体育科学,2005,25(7):35-38
4.李春盛,顾伟等 充血性心力衰竭患者循环内皮细胞、血乳酸和一氧化氮浓度的变化(J)中华急诊医学杂志,2005,14(4):313-315
5.Pacold I,Ackerman L,et al.The effects of acute hypertriglyceridemia and high levels of free fatty acids on left ventricular function(J).Am Heart J,1985,110(4):836-840
6.陈炬,李少华等,TMLR对缺血心肌乳酸代谢及线粒体的影响(J)中国病理生理杂志,2004,20(12):2219-2222
7.Javier A,Wendy K,et al.The use and clinical importance of a Substrate Specific Electrode for rapid determination of blood lactate concentrations(J)JAMA,1995,14(3):221
8.Pellerin L,Halestrap AP,et al,Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain(J)Neurosci Res,2005,79:55-64
9.Goldman SA,Pulsinelli WA,et al.The effects of extracelluar acidosis on neurons and glia in vitro.(J)Cereb Blood Flow Metab,1989,9(4):471
10.杜敏逸,周源等,利多卡因对乳酸损害脑细胞的保护作用(J)中华麻醉学杂志,1995,15(9).406-408
11.赵玉武,丁素菊等,硫酸镁对大鼠脑缺血及再灌注时细胞外液谷氨酸、葡萄糖和乳酸的影响,(J)第二军医大学学报,2004,25(10):1108-1110
12.Cater HL,Benham CD,et al,Neuroprotective role of monocarboxylate transport during glucose deprivation in slice cultures of rat hippocampus(J)J Physiol,2001,531(2):459
13.Sakurai T,Yang B,et al.Synaptic adaptation to repeated hypoglycemia depends.on the utilizationg of monocarboxylates in guinea pig hippocampal slices(J).Diabetes,2002,51:430
14.Bliss TM,Cheng E,et al.Dual-gene,dual-cell type therapy against an excitotoxic insult by bolstering neuroener-getics(J).J Neurosci,2004,24(27):6202
15.王静,刘洪涛等,运动性中枢疲劳及乳酸对大鼠大脑皮质神经细胞MCT mRNA表达的影响,(J)中国运动医学杂志,2007,26(1):52-55
16.Krista B,Halling,et al.Evaluation of oxidative stress markers for the early diagnosis of allograft rejiection in feline renal allotransplant recipients with normal renal function(J)Can Vet J.2004,45(10):831
17.Racusen LC,Solez K,et al.The Banff 97 working classification of renal allograft pathology.(J)Kidney Int 1999,55:713-723
18.张立,金亦辉等,在无血清培养基中代谢副产物对杂交瘤细胞生长代谢的影响,乳酸的作用。(J)华东理工大学学报,2001,28(2):157-160