重组人促红细胞生成素对慢性肾功能衰竭患者营养状态、红细胞免疫及血FDP浓度的影响
|
摘要
慢性肾功能衰竭，发生在各种慢性肾实质疾病的基础上，缓慢地出现肾功能减退而至衰竭，是各种肾脏疾病持续发展的共同转归。其往往在肾衰竭期时即出现各种并发症，如贫血、消化系统症状、心血管系统症状、血压升高、血栓、栓塞等。这些患者同时还伴有程度不等的营养不良及免疫力低下等，使CRF患者的生存质量及生存时间缩短。而贫血是慢性肾功能衰竭的一个重要临床表现，并可能是对CRF患者生活质量产生最大负面影响的症状之一。EPO作为促进红细胞生成、增加红细胞容量的内分泌激素，已被人们所熟知，在纠正CRF患者的贫血状态方面已经有了肯定的疗效，并广泛应用于临床。由于晚期肾病患者肾脏产生的EPO已基本停止，只有少量的EPO促使骨髓继续产生红细胞，因此，自从1985年Powell等成功地运用DNA重组技术获得重组人红细胞生成素后，便开始广泛地应用于临床。目前，人们对促红细胞生成素的研究已不仅局限于提高红细胞的数量，还发现它具有保护神经元，促进肠粘膜发育，增强促性腺激素的分泌、增强放疗敏感性等作用，已经成为具有众多生理功能的激素。此外，营养不良、免疫力低下以及体内的高凝状态是CRF患者的主要特征。由于肾功能的减退，使CRF患者长期摄入不足、吸收不良以及体内蛋白质的分解加速造成CRF患者营养状态低下。由于贫血及体内毒素不能排除，使红细胞数量及质量均下降，并且还由于体内循环免疫复合物的增多，导致CRF患者红细胞免疫功能下降，从而使机体免疫力低下，易发生炎症反应，而炎症反应的发生又加重了营养不良。由于体内循环免疫复合物的增多，使补体系统激活，引起血小板等多种物质的活
化，导致体内的高凝物质增多。因此，贫血、营养不良、体内的高凝状态以及红细胞免疫力的低下，均是相互影响的因素。本文研究目的：观察两组使用及未用r-HuEPO的CRF患者血中PA、TRF、RBP、FDP浓度及红细胞C3b受体结合率、红细胞免疫复合物结合率的改变，并计算HB及CRE与上述各指标的相关性，了解r-HuEPO对CRF患者血营养、红细胞免疫功能及体内凝血功能的影响。
实验方法：研究对象分为两组，未用r-HuEPO的CRF患者（20例）以及使用r-HuEPO的CRF患者（25例）。均于清晨空腹状态下采取静脉全血标本，对于使用r-HuEPO的CRF患者于下次透析前采取血标本，尽量减少透析对实验的影响。促红细胞生成素均使用1个月以上。根据红细胞膜上C3b受体可与补体致敏的酵母菌粘附形成花环以及红细胞膜上粘附的IC中C3b分子或抗原补体复合物中的C3b分子与未致敏的酵母菌的酵母多糖粘附形成花环（RBC-IC花环）的原理，将抗凝血用生理盐水清洗3次，配成1.25×107/mlRBC悬液，与补体致敏的酵母菌及未致敏的酵母菌结合。水浴30min后，经固定、染色后，在高倍显微镜下计数RBC-C3b花环率及RBC-IC花环率，以1个红细胞结合2个及2个以上酵母菌为1个花环。分别计算红细胞花环结合百分率，测定红细胞免疫功能。此外，按照ELISA方法，分别将包被人PA、RBP、TRF、FDP抗体与待测血浆中的PA、RBP、TRF、FDP抗原结合，加入酶标抗体后形成复合物。后者与底物作用呈现显色反应的原理，将标本稀释后，经加样、水浴、洗涤、显色、终止等过程后，在酶标仪490nm处测得血中FDP、TFR、PA及RBP的吸光值，并根据标准曲线计算出血中PA、RBP、TRF、FDP的浓度。
实验结果：①未使用r-HuEPO组的PA、RBP、TRF的浓度均低于使用r-HuEPO后的CRF患者组(P<0.05)。②未使用r-HuEPO组的Hb
浓度低于使用r-HuEPO后的CRF患者组(P<0.05)。③未使用r-HuEPO组的FDP浓度明显高于使用r-HuEPO后的CRF患者组（P<0.05）。④CRE浓度在使用及未用r-HuEPO两组患者中无明显差异(P>.05)。⑤使用r-HuEPO的CRF患者较未使用r-HuEPO的CRF患者的血中RBC—C3b花环率明显升高（P<0.05），而RBC—IC花环率则明显降低（P<0.05）。⑥HB与PA、TRF、RPB的浓度呈正相关，与RBC-C3b花环率呈正相关，与FDP的浓度呈负相关。⑦CRE浓度与PA、TRF、RPB的浓度及FDP的浓度均无相关性。与RBC-C3b花环率呈负相关。上述结果说明：CRF患者在贫血改善后，体内红细胞数量增加，红细胞表面的C3b受体的质与量均得到了增加，红细胞表面的CR1负荷减轻，提高了免疫粘附能力，使红细胞的免疫功能得到了提高。此外，规律血液透析能部分清除血液中的循环免疫复合物，使红细胞膜CR1空位增加，同时能定期清除有免疫抑制的物质并清除了体内毒素，从而减轻了对红细胞的破坏，使红细胞免疫功能增强。由于缺血、缺氧程度减轻，酸中毒情况得以改善，使各器官的功能得到恢复，尤其是消化系统功能恢复后，食欲增加，摄入增多，同时吸收功能也得到了改善，营养得以补充。同时由于红细胞免疫功能得到了提高，机体免疫系统也有所恢复，减轻了炎症反应，减少了炎症易感性，使蛋白分解下降，营养状态得到改善。由于体内缺血缺氧状态的改善，使患者微循环得到了改善，加快了促凝物质的代谢，使体内循环免疫复合物减少，并且也减轻了部分凝血因子及凝血酶的活化，从而减少了体内的高凝物质。相关分析的结果也说明患者营养不良的状态、红细胞免疫功能低下以及体内的FDP浓度均与贫血有关，贫血的纠正可以提高患者的生
Chronic renal failure (CRE)is based on all kinds of kidney diseases, slowly appearances the lower renal function until to failure .The CRF patients are always accompanied with many kinds of complications, such as anemia, disfunction of cardiovascar system, disfunction of gastrointestinal tract, thrombose, etc. These patients are also accompanied with malnutrition and lower immunity which cause an unpleased living quality and short-living life. In these complications anemia is perhaps one of the most important features that effect CRF patients. EPO as an endocrine hormone the satisfied effect to correct anemia has been known of us ,which can increase erythropoietin and elevate hematocrit, and has been used extensively from the r-HuEPO was gained by Powell who used DAN recombination technology in 1985. Now, the study of EPO is not confined in increasing the number of RBC, the other more and more physiological functions has been found, such as to protect neuron ,promote intestinal mucosa development ,to increase the gonadotropin releasing.,and to increase the susceptibility to radiopraxis, etc. Nutrition deficiency ,lower immunity and high coagulation state are the main features in CRF patients. Because of the failing of renal function, CRF patients can not ingest and absorb food efficiency in a long time ,then lead to malnutrition. Accumulation of toxin ,anemia, and increasing of immunocompound lead to the lower function of RBC immunity and lower function of body immunity in CRF patients, and thus ,make them easy to get inflammation ,which will worsen malnutrition then. The large number of immunocompound in circulation leads to the action of manyaterials such as complement and platelet, these materials cause the high coagulation state in CRF patients .Therefor, anemia, malnutrition ,increased coagulant materials and lower RBC immunity are the correlate factors react each other in CRF patients. The object of this paper is to observe the concentration change of PA, TRF, RBP, FDP in blood, and the change of RBC-C3bRR and RBC-ICRR in the group with or without r-HuEPO injection ,and calculate the correlation between them and HB or CRE concentration .Method: the study comprised two groups of 45 matched cases ,CRF patients with r-HuEPO injection (25cases),CRF patients without r-HuEPO injection (20cases). Took the all blood samples in the morning. In order to reduce the effect of hemodialysis to the study ,we took the sample in the morning before the next hemodialysis for the patients with r-HuEPO injection. All these patients used the r-HuEPO more than one month. According to the theory of the C3b receptor on the RBC membrane can adhere to saccharomycete sensitized by complement and form a round , and the theory of C3b molecule of IC or antigen-complement compound on RBC membrane can adhere to unsensitized saccharomycete and form a round, we washed the anticoagulate blood sample by normal saline ,made up to 1.25×107/ml RBC solution. Then after mixing the sensitized saccharomycete or unsensitized saccharomycete with these solution, water bathed 30 minutes, fixed ,colored ,counted the round rate with microscope (one RBC was adhered with more than two saccharomycetes is a round) .Besides, according to the ELISA method we added anti-human PA ,RPB ,TRF ,FDP ntibody to enzyme-labeled-antibody, color developed ,and measured the OD value at 490nm, and then calculated the concentration of PA, RBP, TRF, FDP .Rusults :1. HB, PA, RBP, TRF concentration are significantly higher than that in the guoup without r-HuEPO injection (P<0.05). 2. FDP concentration is significantly lower than that in the guoup without r-HuEPO injection (P <0.05). 3. RBC-C3bRR is significantly higher than that in the group without r-HuEPO injection (P<0.05), and RBC-ICRR is significantly lower than that in the group without r-HuEPO injection (P<0.05). 4. The change of CRE concentration is not obvious in the two guoups . 5. There is a positive correlation between HB and PA ,TRF, RBP, RBC-C3bRR,and there is a negative correlation between HB and FDP . 6. N
化，导致体内的高凝物质增多。因此，贫血、营养不良、体内的高凝状态以及红细胞免疫力的低下，均是相互影响的因素。本文研究目的：观察两组使用及未用r-HuEPO的CRF患者血中PA、TRF、RBP、FDP浓度及红细胞C3b受体结合率、红细胞免疫复合物结合率的改变，并计算HB及CRE与上述各指标的相关性，了解r-HuEPO对CRF患者血营养、红细胞免疫功能及体内凝血功能的影响。
实验方法：研究对象分为两组，未用r-HuEPO的CRF患者（20例）以及使用r-HuEPO的CRF患者（25例）。均于清晨空腹状态下采取静脉全血标本，对于使用r-HuEPO的CRF患者于下次透析前采取血标本，尽量减少透析对实验的影响。促红细胞生成素均使用1个月以上。根据红细胞膜上C3b受体可与补体致敏的酵母菌粘附形成花环以及红细胞膜上粘附的IC中C3b分子或抗原补体复合物中的C3b分子与未致敏的酵母菌的酵母多糖粘附形成花环（RBC-IC花环）的原理，将抗凝血用生理盐水清洗3次，配成1.25×107/mlRBC悬液，与补体致敏的酵母菌及未致敏的酵母菌结合。水浴30min后，经固定、染色后，在高倍显微镜下计数RBC-C3b花环率及RBC-IC花环率，以1个红细胞结合2个及2个以上酵母菌为1个花环。分别计算红细胞花环结合百分率，测定红细胞免疫功能。此外，按照ELISA方法，分别将包被人PA、RBP、TRF、FDP抗体与待测血浆中的PA、RBP、TRF、FDP抗原结合，加入酶标抗体后形成复合物。后者与底物作用呈现显色反应的原理，将标本稀释后，经加样、水浴、洗涤、显色、终止等过程后，在酶标仪490nm处测得血中FDP、TFR、PA及RBP的吸光值，并根据标准曲线计算出血中PA、RBP、TRF、FDP的浓度。
实验结果：①未使用r-HuEPO组的PA、RBP、TRF的浓度均低于使用r-HuEPO后的CRF患者组(P<0.05)。②未使用r-HuEPO组的Hb
浓度低于使用r-HuEPO后的CRF患者组(P<0.05)。③未使用r-HuEPO组的FDP浓度明显高于使用r-HuEPO后的CRF患者组（P<0.05）。④CRE浓度在使用及未用r-HuEPO两组患者中无明显差异(P>.05)。⑤使用r-HuEPO的CRF患者较未使用r-HuEPO的CRF患者的血中RBC—C3b花环率明显升高（P<0.05），而RBC—IC花环率则明显降低（P<0.05）。⑥HB与PA、TRF、RPB的浓度呈正相关，与RBC-C3b花环率呈正相关，与FDP的浓度呈负相关。⑦CRE浓度与PA、TRF、RPB的浓度及FDP的浓度均无相关性。与RBC-C3b花环率呈负相关。上述结果说明：CRF患者在贫血改善后，体内红细胞数量增加，红细胞表面的C3b受体的质与量均得到了增加，红细胞表面的CR1负荷减轻，提高了免疫粘附能力，使红细胞的免疫功能得到了提高。此外，规律血液透析能部分清除血液中的循环免疫复合物，使红细胞膜CR1空位增加，同时能定期清除有免疫抑制的物质并清除了体内毒素，从而减轻了对红细胞的破坏，使红细胞免疫功能增强。由于缺血、缺氧程度减轻，酸中毒情况得以改善，使各器官的功能得到恢复，尤其是消化系统功能恢复后，食欲增加，摄入增多，同时吸收功能也得到了改善，营养得以补充。同时由于红细胞免疫功能得到了提高，机体免疫系统也有所恢复，减轻了炎症反应，减少了炎症易感性，使蛋白分解下降，营养状态得到改善。由于体内缺血缺氧状态的改善，使患者微循环得到了改善，加快了促凝物质的代谢，使体内循环免疫复合物减少，并且也减轻了部分凝血因子及凝血酶的活化，从而减少了体内的高凝物质。相关分析的结果也说明患者营养不良的状态、红细胞免疫功能低下以及体内的FDP浓度均与贫血有关，贫血的纠正可以提高患者的生
Chronic renal failure (CRE)is based on all kinds of kidney diseases, slowly appearances the lower renal function until to failure .The CRF patients are always accompanied with many kinds of complications, such as anemia, disfunction of cardiovascar system, disfunction of gastrointestinal tract, thrombose, etc. These patients are also accompanied with malnutrition and lower immunity which cause an unpleased living quality and short-living life. In these complications anemia is perhaps one of the most important features that effect CRF patients. EPO as an endocrine hormone the satisfied effect to correct anemia has been known of us ,which can increase erythropoietin and elevate hematocrit, and has been used extensively from the r-HuEPO was gained by Powell who used DAN recombination technology in 1985. Now, the study of EPO is not confined in increasing the number of RBC, the other more and more physiological functions has been found, such as to protect neuron ,promote intestinal mucosa development ,to increase the gonadotropin releasing.,and to increase the susceptibility to radiopraxis, etc. Nutrition deficiency ,lower immunity and high coagulation state are the main features in CRF patients. Because of the failing of renal function, CRF patients can not ingest and absorb food efficiency in a long time ,then lead to malnutrition. Accumulation of toxin ,anemia, and increasing of immunocompound lead to the lower function of RBC immunity and lower function of body immunity in CRF patients, and thus ,make them easy to get inflammation ,which will worsen malnutrition then. The large number of immunocompound in circulation leads to the action of many
引文
1. 梁馨苓、史伟、刘双信、叶智明、何朝生、梁永正，尿毒症血液透析患者炎症反应与营养状态及贫血的关系，广东医学，2003，24：353-354。
2. 徐洪实、梅长林、张斌、张翼翔、陈蕾，左卡尼汀对尿毒症血透病人营养不良的改善作用，中国新药与临床杂志，2001，20：41-42。
3. Seigel I, Lin TL, Gieicher, The red cell immune system ，Lancet,1981,2:556.
4.周立红、刘敏涓、石惠敏、刘兰平、刘泽霖，慢性肾功能衰竭血液透析对纤维蛋白原的影响，中原医刊，2002，27（2）：28-29。
5. Marckmann P. Nutritional status of patients on hemodialysis and peritoneal dialysis.Clin Nephrol,1998,29:75—78.
6. 郭峰、钱宝华、张乐之，现代红细胞免疫学，2002年6月出版。
7. 路建铙、陈丽君、詹子华、张金元、周月红、李秋丽,30例尿毒症患者红细胞免疫功能的研究,中国免疫学杂志,1991,7:55-56。
8. 苗里宁、顾华、董云珠，慢性肾功能不全红细胞免疫研究,中华肾脏病杂志,1992,8:280-281。
9. 顾华、苗里宁、王中华,慢性肾炎红细胞免疫粘附功能测定,白求恩医科大学学报,1988,14(1):49-50。
10. Goicoechea M, Vanzquez M I, Ruiz MA , Intravenous calcitriol improves anemia and reduces the need for erythropoietin in hemodialysis patients, Nephron, 1998,78(1):23-27.
11、王海滨、张景萍、郭峰等，血细胞天然免疫粘附肿瘤细胞的现象及意义，中华微生物学和免疫学杂志，2001，21（1）：263。
12. Albital S, Genin R, Fen Chong M, et al, High-dose alfacalcidol improves anemia in patients on hemodialysis, Nephrol Dial Transplant, 1997,12:514-518.
13. Guarnieri G, Toigo G, Fiotti, et al, Mechanisms of malnutrition in uremia, Kidney Int, 1997,52,suppl,625-41~42.
14. Schaefer RM, Schaefer L, Horl WH, Mechanisms for protein catabolism in acute renal failure, Nephrol dial Transplant Suppl, 1994,3:44-47.
15. David R., Susan MC, Charles MS, et al, Correction of acidosis in humans with CRF decreases protein degradation and amino acid oxidation, Am J Physiol, 1993,265:E 230-235.
16. Mitch WE, Jurkovitz C, England BK,Mechanisms that cause protein and amino acid catabolism in uremia.，Am J Kidney Dis, 1993,21(1):91-95.
17. Zimmerman J, Herrlinger S, Pruy A, et al, C-reactive protein as a marker of chronic inflammation in uremic patients，Blood Purif,2000,18:183-190.
18. Kaysen GA, Subin JA,Muller HG, et al, The actue-phase reponse varies with time and serum albumin levels in hemodialysis patients, Kidney Inter, 2000,58:346.
19. Bergstrom J, Lindholm B,Malnutrition, Cadiac disease and mortality: an integrated point of view,Am J Kidney Dis, 1998,32:834-841.
20．Ziegler TR, Lazarus JM, Young LS, et al, Effects of recombinant human growth hormone in adults receiving maintenance hemodialysis, J Am Soc Nephrd,1991,2:1130-1135.
21.Johannsson G, Bengtsson BA, Ahlmen J, Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: anabolic effect and functional improvement. Am J Kidney Dis, 1999,33(4):709-717.
22. Saxena R,Batra VV, Sighn ND, Prothrombotic Factors in nephritic syndrome, Indian J Pathol Microbiol,2000,43:319-323.
23. Oviasu E, Famoclu AA,Ojeh EA, Plasma viscosity in nephritic nigrans, Clin Hemorheol Microcire,1998,19:163-167.
24. Shultz PJ, Raij L, Effect of amlodipine on mesangial cell proliferation and protein synthesis, Am J Hypertens,1992,5:912-914.
25. Kaizuka M, Yamabe H, Osawa H, et al, Thrombin stimulates synthesis of type IV collagen and tissue inhibitor of metalloproteinases-1 by cultured human mesangial cells, J Am Soc Nephrol,1999,10:1516-1523.
26. Yamabe H, Osawa H,Inuma H, et al, Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells, Nephrol Dial Transplant,1997,12:438-442.
27. Idasiak-Piechocka I, Krzymanski M, The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis, Przegl Lek,1996,53:443-453.
28. Rychlik I, Andrassy K, Waldherr R,Clinical features and natural history of IgA nephropathy, Ann Med Interne,1999,150:117-126.
29. 候振江,D-二聚体测定的临床应用,临床检验杂志,1997,15:63-64。
30. 孙雪峰、周希静、王力宁,糖尿病肾病患者尿FDP/尿蛋白比值检测的临床意义,中国中西医结合肾病杂志,2002,3(8):457-459。
2. 徐洪实、梅长林、张斌、张翼翔、陈蕾，左卡尼汀对尿毒症血透病人营养不良的改善作用，中国新药与临床杂志，2001，20：41-42。
3. Seigel I, Lin TL, Gieicher, The red cell immune system ，Lancet,1981,2:556.
4.周立红、刘敏涓、石惠敏、刘兰平、刘泽霖，慢性肾功能衰竭血液透析对纤维蛋白原的影响，中原医刊，2002，27（2）：28-29。
5. Marckmann P. Nutritional status of patients on hemodialysis and peritoneal dialysis.Clin Nephrol,1998,29:75—78.
6. 郭峰、钱宝华、张乐之，现代红细胞免疫学，2002年6月出版。
7. 路建铙、陈丽君、詹子华、张金元、周月红、李秋丽,30例尿毒症患者红细胞免疫功能的研究,中国免疫学杂志,1991,7:55-56。
8. 苗里宁、顾华、董云珠，慢性肾功能不全红细胞免疫研究,中华肾脏病杂志,1992,8:280-281。
9. 顾华、苗里宁、王中华,慢性肾炎红细胞免疫粘附功能测定,白求恩医科大学学报,1988,14(1):49-50。
10. Goicoechea M, Vanzquez M I, Ruiz MA , Intravenous calcitriol improves anemia and reduces the need for erythropoietin in hemodialysis patients, Nephron, 1998,78(1):23-27.
11、王海滨、张景萍、郭峰等，血细胞天然免疫粘附肿瘤细胞的现象及意义，中华微生物学和免疫学杂志，2001，21（1）：263。
12. Albital S, Genin R, Fen Chong M, et al, High-dose alfacalcidol improves anemia in patients on hemodialysis, Nephrol Dial Transplant, 1997,12:514-518.
13. Guarnieri G, Toigo G, Fiotti, et al, Mechanisms of malnutrition in uremia, Kidney Int, 1997,52,suppl,625-41~42.
14. Schaefer RM, Schaefer L, Horl WH, Mechanisms for protein catabolism in acute renal failure, Nephrol dial Transplant Suppl, 1994,3:44-47.
15. David R., Susan MC, Charles MS, et al, Correction of acidosis in humans with CRF decreases protein degradation and amino acid oxidation, Am J Physiol, 1993,265:E 230-235.
16. Mitch WE, Jurkovitz C, England BK,Mechanisms that cause protein and amino acid catabolism in uremia.，Am J Kidney Dis, 1993,21(1):91-95.
17. Zimmerman J, Herrlinger S, Pruy A, et al, C-reactive protein as a marker of chronic inflammation in uremic patients，Blood Purif,2000,18:183-190.
18. Kaysen GA, Subin JA,Muller HG, et al, The actue-phase reponse varies with time and serum albumin levels in hemodialysis patients, Kidney Inter, 2000,58:346.
19. Bergstrom J, Lindholm B,Malnutrition, Cadiac disease and mortality: an integrated point of view,Am J Kidney Dis, 1998,32:834-841.
20．Ziegler TR, Lazarus JM, Young LS, et al, Effects of recombinant human growth hormone in adults receiving maintenance hemodialysis, J Am Soc Nephrd,1991,2:1130-1135.
21.Johannsson G, Bengtsson BA, Ahlmen J, Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: anabolic effect and functional improvement. Am J Kidney Dis, 1999,33(4):709-717.
22. Saxena R,Batra VV, Sighn ND, Prothrombotic Factors in nephritic syndrome, Indian J Pathol Microbiol,2000,43:319-323.
23. Oviasu E, Famoclu AA,Ojeh EA, Plasma viscosity in nephritic nigrans, Clin Hemorheol Microcire,1998,19:163-167.
24. Shultz PJ, Raij L, Effect of amlodipine on mesangial cell proliferation and protein synthesis, Am J Hypertens,1992,5:912-914.
25. Kaizuka M, Yamabe H, Osawa H, et al, Thrombin stimulates synthesis of type IV collagen and tissue inhibitor of metalloproteinases-1 by cultured human mesangial cells, J Am Soc Nephrol,1999,10:1516-1523.
26. Yamabe H, Osawa H,Inuma H, et al, Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells, Nephrol Dial Transplant,1997,12:438-442.
27. Idasiak-Piechocka I, Krzymanski M, The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis, Przegl Lek,1996,53:443-453.
28. Rychlik I, Andrassy K, Waldherr R,Clinical features and natural history of IgA nephropathy, Ann Med Interne,1999,150:117-126.
29. 候振江,D-二聚体测定的临床应用,临床检验杂志,1997,15:63-64。
30. 孙雪峰、周希静、王力宁,糖尿病肾病患者尿FDP/尿蛋白比值检测的临床意义,中国中西医结合肾病杂志,2002,3(8):457-459。