阿法D_3冲击治疗对尿毒症患者钙、磷代谢和IL-2、SIL-2R的影响
摘要
前言
活性维生素D即1.25(OH)_2D_3缺乏是慢性肾功不全(CRF)尿毒症患者低血钙，高血磷，继发性甲状旁腺机能亢进(SHPT)及免疫功能紊乱的重要发病机制。国外近期的研究提示，活性维生素D与皮质醇激素有着同源基因，可在T细胞mRNA的水平上抑制白细胞介素2(IL-2)合成，致使可溶性白细胞介素2受体(SIL-2R)代偿升高，有免疫抑制作用。维生素D能强烈阻止甲状旁腺素(PTH)的分泌；而PTH却有同维生素D相似的降IL-2升SIL-2R的功能。因此维生素D对尿毒症患者免疫状态的影响仍存有争议。
维生素D应用于尿毒症患者之后，其最佳的治疗剂量及方式受到重视，现已证实1.25(OH)_2D_3冲击治疗疗效迅速，但也存在高钙血症的副作用；与1.25(OH)_2D_3相比，阿法D_3(αD_3)仅C_1位上有羟基，在肠道中没有直接活性；另外αD_3半衰期较长，血药浓度稳定。应用αD_3冲击治疗，国内外尚无报道。本研究对应用不同剂量方法的αD_3对55例尿毒症患者进行了治疗观察，目的在于①选择一种安全有效的科学的投药方式，②观察对免疫功能的影响。并初步探讨了相关机制，现报告如下。
实验材料
1．病例选择：非透析CRF尿毒症患者55例，同时伴有低血钙、高血磷及SHPT，年龄44.7±10.1岁。实验前至少2周内未用过钙、维生素D制剂及皮质醇激素类能影响免疫功能的药物。病人随机分为两组，冲击组30例，常规治疗组25例，正常对照人群
组ro例。病例组患者和正常对照者之间年龄、性别相匹配。
2.实验仪器:DP IMMUllTE化学发光免疫分析仪，日立7170
自动生化分析仪，SLT SPECTRAM酶标仪。
3.实验试剂:PI’H化学发光免疫试剂盒购于天津德普公司，IL
一2与SIL一ZR试剂盒购于美国贝克曼公司。
实验方法
1.标本采集
所有病例在治疗前均空腹采血常规检测血钙、血磷、ALT，而
PrH、IL一2、slL一ZR分离血清低温保存，统一批量检测。冲击治
疗组给于。D31卜g日一次口服，同时碳酸钙(CaCo，)0.5日一次口
服;常规治疗组aD30.25协g日一次口服，同时CaCO，也。.5日一
次口服，2组其它的治疗完全一致。服药两周后，与正常对照组一
起，重新检测上述指标。
2.检测方法
(1)ALT:Karmen比色法。
(2)血钙:偶氮肿111法。
(3)血磷:直接紫外法。血钙、磷、ALT均应用日立7170自动
生化分析仪。
(4) PrH:化学发光酶免疫分析法进行检测。
(5)sIL一ZR:化学发光酶免疫分析法。与PTH同样应用DP
IMMuLITE分析仪检测。
(6)IL一2:酶联免疫吸附实验双抗体夹心法。应用SLT
SPECTRAM酶标仪。
3.统计学处理
各检测指标用均值土标准差(x王sD)表示，同一组治疗前后
数据用配对t检验，不同组间数据的比较用两组间t检验，P<0.05
为有显著性差异。
实验结果
CRF患者与正常人群相对比，血钙水平降低24.8%(P<
0.01)，IL一2减少了35.2%(P<0.05)。血磷升高了65.2%，SIL
一ZR增加了3.67倍，PTH也上升10.1倍，差异著显(P<0.01)。
ALT的变化(P>0.1)无意义。
常规组治疗前后相比较，PrH下降32.1%(573.16士414.39
vs389.17士181.86 Pg/Inl，P<0.05);血磷、SIL一ZR分别下降了
3.51%及3.86%(P>0.05)，而血钙、IL一2则轻度上升了4.14%
与0.1%(P>0.05)后四项变化都无统计学意义。ALT的变化也
不明显(P>0.1)。
冲击组治疗前后各观测指标(ALT除外)相比较均有明显变
化。件H下降了59.9%(562.06士403.22vs225.24士175.45p岁
耐，p<0.01);血磷降低26.2%(2.29土0.69vsr.69士0.65 mmoF
l，);IL一2下降17.6%(5.28士2.03v科.32士2.17林群L);血钙上
升22 .1%(1 .90土0.3Ivs2.32士0.24 mmoFI);SIL一ZR增加
14.1%(1770.32土873.79vsl551.64土857.96 IU/耐，P<0.05)。
冲击组与常规组治疗后的结果相比较，血钙:2.32土0.24vs
2 .01士0 .1 8 mmoFL;SIL一ZR:1770.32士873.79vs1519.52土
624.78IU/Inl;血磷:1 .69士0.65vs2一9土0.49 nunoFL:IL一2:4.32
土2 .17vs5‘33土1 .83协岁IJ;件H:225.24士175.45vs389.17土
181.86P酬耐，其变化均有显著性差异(P<0.05)。ALT无变化
(P>0 .1)。
全部患者在治疗过程中，未发现高钙血症，无烦渴、多尿、恶
心、呕吐等维生素D中毒症状。每例ALT在正常范围内。
讨论
肾脏la经化酶是合成活性维生素D的主要限速酶，由于尿
毒症患者肾组织的毁损，1。经化酶的活性及数量均下降，活性维
生素D产量不足，是导致低血钙、高血磷、SHPr的首要原因。
对于CRF尿毒症患者，肾小球滤过率(GFR)明显低下，PI’H
代偿性升高也不足以促使血磷有效排出。相反，PTH持续升高，
其溶骨作用表现突出，这样血磷更高，反馈抑制活性维生素D合
成，使血钙更低，导致SH件更趋恶化，形成恶性循环，即出现了矫
枉失衡现象。
尿毒症病人的免疫功能紊乱，是多方面综合因素所形成，多存
在IL一2的减少及SIL一ZR的增高。现已公认，PrH可抑制IL一2
生成，代偿性SIL一ZR增多，对免疫系统有抑制作用。本实验结果
示尿毒症患者较正常人IL一2下降了35.2%，SIL一ZR增加了
Preface
Because of active vitamin D also named 1. 25(OH)2D3 declining ,the most of chronic renal failure uremic patients have to endure hy-pocalcemia, hypophosphatemia, secondary hyperparathyroidism (SHPT) and immunity confusion. aD3 is nonactive vitamin D before C25 hydrooxyaction in liver cell, so it become 1.25(OH)2D3. The active vitamin D can improve Ca, P to be absorbed in intestine and renal tube and inhibit parathyroid cell proliferation to decrease the product of PTH. Some foreign latest research show the active vitamin D can inhibit the synthesis of IL -2 and Ig . As a result the SIL-2R increases compensatedly. The active vitamin D is like cortisone with immu-nosuppressive activity. The controversy has been existing in which is the best administration and the immunoregulationn to uremic patents since the vitamin D was adopted. Some scholars believe vitamin D routine therapy with few adverse reactions. But the other think the vitamin D pulse therapy is more reliable than routine therapy which only compensates physiological requirements . There are few reports on aD3 pulse therapy. This experiment will aim at discussing the curative affection on Ca, P, SHPT and immunity between the routine and pulse administration, while establishing secured rapid and beneficial treatment. Now I will show the result;
Material
1. Sample: 55 nondialysis urimic patients with hypocalcemia, hy-
perphosphatemia and SHPT, age 44. 7±10. 1 years old. They have not adopted Ca, vitamin D, and cortisone. To divide the patients into two teams at random the pulse therapy team including 30 person; the routine therapy team including 25 person. The control team is composed of 10 health person who were in harmony with uremic patients in age and sex.
2. Apparatus: DP IMMULTTE ANALYSOR. HITACH 7170 AUTOMATIC BIOCHEMISTRY ANALYSOR.
3. Reagent. PTH reagent from DP COMPANY. IL-2, SIL-2R regent from BECKMAN COMPANY.
Method
First, to take venous blood of all sample with empty stomach before experiment and to examine Ca, P, PTH, IL-2, SIL-2R and ALT. Second , the person in pulse team administer aD3 1ug and Ca-CO3 0. 5 Qd Po, as well as the person in routine team take aD30. 25ug and CaCO3 0. 5 Qd Po. The other treatments are same. I will test those indexes again after two weeks. Third, the data was statistically analyzed. To express all tested indexes in form of mean ± SD. Student s t test, P <0. 05 as significant limit.
Result
CRF vs control: the Ca. concentration came down by 24. 8% (1. 91 ±0.28vs2.54±0.16mmol/l p <0.01) ;IL-2 dropped by 35.2% (5.31±2. 07vs8. 19±2. 17ug/L p<0.05) The P concentration increased by 65.2%(2.28±0.68vsl.38±0.11mmol/1) ;the SIL-2R
grew by 3. 67 folds(1561±637. 06vs334 ± 181IU/mi) , as weU as PTH rising 10. 1folds(p <0. 01).
The routine team self - contrast: PTH declined 32. 1% (573. 16 ±414. 39vs389. 17 ± 181. 86Pg/ml p <0. 05). But the variances of P, SIL - 2R, Ca, IL - 2 and ALT are not significant (P>0.05 ).
The self - contrast in pulse team. PTH descended 59. 9% (562. 06 ±403. 22 vs225. 4±175. 45Pg/ml P <0.01). P concentration was fallen by 26.2% (2. 29 ±0. 69vsl. 69 ±0. 65mmol/l) ;IL-2 went down by 17. 6% ( 5. 28 ± 2. 03vs4. 32 ± 2. 17ug/L) ; Ca was raised by 22. 1% ( 1. 90 ± 0. 31vs2. 32 ± 0. 24mmol/L); SIL-2R went up 14. 1% (1770. 32±873. 79vs1551. 64 ± 857. 96IU/ml p < 0.05).
The tested indexes of pulse therapy vs those of routine team: Ca 2. 32 ± 0. 24vs2. 01 ± 0. 18mmol/L; SIL - 2R 1770. 32 ± 873.79 vsl519.52±624.78IU/ml;P 1.69 ±0. 65vs2. 19 ±0. 49mmol/L;IL -24. 32 ±2. 17vs5.33 ± 1. 83ug/L;PTH 225. 24 ± 1775.43vs389. 17 ± 181. 86Pg/ml. P <0. 05. There were not hypercalcemia during experiment. I also did not find progressive nausea and vomiting. Each ALT is not beyond the normal limitation.
Discuss
The shortage of active vitamin D is the primary cause of hypocal-cemia, hyperphosphatemia and SHPT. Kidney is an important organ where the active vitamin D is synthesized.
Because of the impaired kidney falls the quantity and activity of
活性维生素D即1.25(OH)_2D_3缺乏是慢性肾功不全(CRF)尿毒症患者低血钙，高血磷，继发性甲状旁腺机能亢进(SHPT)及免疫功能紊乱的重要发病机制。国外近期的研究提示，活性维生素D与皮质醇激素有着同源基因，可在T细胞mRNA的水平上抑制白细胞介素2(IL-2)合成，致使可溶性白细胞介素2受体(SIL-2R)代偿升高，有免疫抑制作用。维生素D能强烈阻止甲状旁腺素(PTH)的分泌；而PTH却有同维生素D相似的降IL-2升SIL-2R的功能。因此维生素D对尿毒症患者免疫状态的影响仍存有争议。
维生素D应用于尿毒症患者之后，其最佳的治疗剂量及方式受到重视，现已证实1.25(OH)_2D_3冲击治疗疗效迅速，但也存在高钙血症的副作用；与1.25(OH)_2D_3相比，阿法D_3(αD_3)仅C_1位上有羟基，在肠道中没有直接活性；另外αD_3半衰期较长，血药浓度稳定。应用αD_3冲击治疗，国内外尚无报道。本研究对应用不同剂量方法的αD_3对55例尿毒症患者进行了治疗观察，目的在于①选择一种安全有效的科学的投药方式，②观察对免疫功能的影响。并初步探讨了相关机制，现报告如下。
实验材料
1．病例选择：非透析CRF尿毒症患者55例，同时伴有低血钙、高血磷及SHPT，年龄44.7±10.1岁。实验前至少2周内未用过钙、维生素D制剂及皮质醇激素类能影响免疫功能的药物。病人随机分为两组，冲击组30例，常规治疗组25例，正常对照人群
组ro例。病例组患者和正常对照者之间年龄、性别相匹配。
2.实验仪器:DP IMMUllTE化学发光免疫分析仪，日立7170
自动生化分析仪，SLT SPECTRAM酶标仪。
3.实验试剂:PI’H化学发光免疫试剂盒购于天津德普公司，IL
一2与SIL一ZR试剂盒购于美国贝克曼公司。
实验方法
1.标本采集
所有病例在治疗前均空腹采血常规检测血钙、血磷、ALT，而
PrH、IL一2、slL一ZR分离血清低温保存，统一批量检测。冲击治
疗组给于。D31卜g日一次口服，同时碳酸钙(CaCo，)0.5日一次口
服;常规治疗组aD30.25协g日一次口服，同时CaCO，也。.5日一
次口服，2组其它的治疗完全一致。服药两周后，与正常对照组一
起，重新检测上述指标。
2.检测方法
(1)ALT:Karmen比色法。
(2)血钙:偶氮肿111法。
(3)血磷:直接紫外法。血钙、磷、ALT均应用日立7170自动
生化分析仪。
(4) PrH:化学发光酶免疫分析法进行检测。
(5)sIL一ZR:化学发光酶免疫分析法。与PTH同样应用DP
IMMuLITE分析仪检测。
(6)IL一2:酶联免疫吸附实验双抗体夹心法。应用SLT
SPECTRAM酶标仪。
3.统计学处理
各检测指标用均值土标准差(x王sD)表示，同一组治疗前后
数据用配对t检验，不同组间数据的比较用两组间t检验，P<0.05
为有显著性差异。
实验结果
CRF患者与正常人群相对比，血钙水平降低24.8%(P<
0.01)，IL一2减少了35.2%(P<0.05)。血磷升高了65.2%，SIL
一ZR增加了3.67倍，PTH也上升10.1倍，差异著显(P<0.01)。
ALT的变化(P>0.1)无意义。
常规组治疗前后相比较，PrH下降32.1%(573.16士414.39
vs389.17士181.86 Pg/Inl，P<0.05);血磷、SIL一ZR分别下降了
3.51%及3.86%(P>0.05)，而血钙、IL一2则轻度上升了4.14%
与0.1%(P>0.05)后四项变化都无统计学意义。ALT的变化也
不明显(P>0.1)。
冲击组治疗前后各观测指标(ALT除外)相比较均有明显变
化。件H下降了59.9%(562.06士403.22vs225.24士175.45p岁
耐，p<0.01);血磷降低26.2%(2.29土0.69vsr.69士0.65 mmoF
l，);IL一2下降17.6%(5.28士2.03v科.32士2.17林群L);血钙上
升22 .1%(1 .90土0.3Ivs2.32士0.24 mmoFI);SIL一ZR增加
14.1%(1770.32土873.79vsl551.64土857.96 IU/耐，P<0.05)。
冲击组与常规组治疗后的结果相比较，血钙:2.32土0.24vs
2 .01士0 .1 8 mmoFL;SIL一ZR:1770.32士873.79vs1519.52土
624.78IU/Inl;血磷:1 .69士0.65vs2一9土0.49 nunoFL:IL一2:4.32
土2 .17vs5‘33土1 .83协岁IJ;件H:225.24士175.45vs389.17土
181.86P酬耐，其变化均有显著性差异(P<0.05)。ALT无变化
(P>0 .1)。
全部患者在治疗过程中，未发现高钙血症，无烦渴、多尿、恶
心、呕吐等维生素D中毒症状。每例ALT在正常范围内。
讨论
肾脏la经化酶是合成活性维生素D的主要限速酶，由于尿
毒症患者肾组织的毁损，1。经化酶的活性及数量均下降，活性维
生素D产量不足，是导致低血钙、高血磷、SHPr的首要原因。
对于CRF尿毒症患者，肾小球滤过率(GFR)明显低下，PI’H
代偿性升高也不足以促使血磷有效排出。相反，PTH持续升高，
其溶骨作用表现突出，这样血磷更高，反馈抑制活性维生素D合
成，使血钙更低，导致SH件更趋恶化，形成恶性循环，即出现了矫
枉失衡现象。
尿毒症病人的免疫功能紊乱，是多方面综合因素所形成，多存
在IL一2的减少及SIL一ZR的增高。现已公认，PrH可抑制IL一2
生成，代偿性SIL一ZR增多，对免疫系统有抑制作用。本实验结果
示尿毒症患者较正常人IL一2下降了35.2%，SIL一ZR增加了
Preface
Because of active vitamin D also named 1. 25(OH)2D3 declining ,the most of chronic renal failure uremic patients have to endure hy-pocalcemia, hypophosphatemia, secondary hyperparathyroidism (SHPT) and immunity confusion. aD3 is nonactive vitamin D before C25 hydrooxyaction in liver cell, so it become 1.25(OH)2D3. The active vitamin D can improve Ca, P to be absorbed in intestine and renal tube and inhibit parathyroid cell proliferation to decrease the product of PTH. Some foreign latest research show the active vitamin D can inhibit the synthesis of IL -2 and Ig . As a result the SIL-2R increases compensatedly. The active vitamin D is like cortisone with immu-nosuppressive activity. The controversy has been existing in which is the best administration and the immunoregulationn to uremic patents since the vitamin D was adopted. Some scholars believe vitamin D routine therapy with few adverse reactions. But the other think the vitamin D pulse therapy is more reliable than routine therapy which only compensates physiological requirements . There are few reports on aD3 pulse therapy. This experiment will aim at discussing the curative affection on Ca, P, SHPT and immunity between the routine and pulse administration, while establishing secured rapid and beneficial treatment. Now I will show the result;
Material
1. Sample: 55 nondialysis urimic patients with hypocalcemia, hy-
perphosphatemia and SHPT, age 44. 7±10. 1 years old. They have not adopted Ca, vitamin D, and cortisone. To divide the patients into two teams at random the pulse therapy team including 30 person; the routine therapy team including 25 person. The control team is composed of 10 health person who were in harmony with uremic patients in age and sex.
2. Apparatus: DP IMMULTTE ANALYSOR. HITACH 7170 AUTOMATIC BIOCHEMISTRY ANALYSOR.
3. Reagent. PTH reagent from DP COMPANY. IL-2, SIL-2R regent from BECKMAN COMPANY.
Method
First, to take venous blood of all sample with empty stomach before experiment and to examine Ca, P, PTH, IL-2, SIL-2R and ALT. Second , the person in pulse team administer aD3 1ug and Ca-CO3 0. 5 Qd Po, as well as the person in routine team take aD30. 25ug and CaCO3 0. 5 Qd Po. The other treatments are same. I will test those indexes again after two weeks. Third, the data was statistically analyzed. To express all tested indexes in form of mean ± SD. Student s t test, P <0. 05 as significant limit.
Result
CRF vs control: the Ca. concentration came down by 24. 8% (1. 91 ±0.28vs2.54±0.16mmol/l p <0.01) ;IL-2 dropped by 35.2% (5.31±2. 07vs8. 19±2. 17ug/L p<0.05) The P concentration increased by 65.2%(2.28±0.68vsl.38±0.11mmol/1) ;the SIL-2R
grew by 3. 67 folds(1561±637. 06vs334 ± 181IU/mi) , as weU as PTH rising 10. 1folds(p <0. 01).
The routine team self - contrast: PTH declined 32. 1% (573. 16 ±414. 39vs389. 17 ± 181. 86Pg/ml p <0. 05). But the variances of P, SIL - 2R, Ca, IL - 2 and ALT are not significant (P>0.05 ).
The self - contrast in pulse team. PTH descended 59. 9% (562. 06 ±403. 22 vs225. 4±175. 45Pg/ml P <0.01). P concentration was fallen by 26.2% (2. 29 ±0. 69vsl. 69 ±0. 65mmol/l) ;IL-2 went down by 17. 6% ( 5. 28 ± 2. 03vs4. 32 ± 2. 17ug/L) ; Ca was raised by 22. 1% ( 1. 90 ± 0. 31vs2. 32 ± 0. 24mmol/L); SIL-2R went up 14. 1% (1770. 32±873. 79vs1551. 64 ± 857. 96IU/ml p < 0.05).
The tested indexes of pulse therapy vs those of routine team: Ca 2. 32 ± 0. 24vs2. 01 ± 0. 18mmol/L; SIL - 2R 1770. 32 ± 873.79 vsl519.52±624.78IU/ml;P 1.69 ±0. 65vs2. 19 ±0. 49mmol/L;IL -24. 32 ±2. 17vs5.33 ± 1. 83ug/L;PTH 225. 24 ± 1775.43vs389. 17 ± 181. 86Pg/ml. P <0. 05. There were not hypercalcemia during experiment. I also did not find progressive nausea and vomiting. Each ALT is not beyond the normal limitation.
Discuss
The shortage of active vitamin D is the primary cause of hypocal-cemia, hyperphosphatemia and SHPT. Kidney is an important organ where the active vitamin D is synthesized.
Because of the impaired kidney falls the quantity and activity of
引文
1． Mortingu I,Sarachor M.The importance of dietary calcium and phosphorus in the secondary hyperpara thyroidism of patients with early renal failkure.Am J kidney dis,1997 29(4) :496．
2． Baylink DJ Calcium and bone homeostasis and changes with aging principle of geriatric medicine.Third Edition.Mcgran-Hill Inc.Pubs chapter 1998,78-87
3． Eastellr Y.Interrelationship among VD metabolism,true calcium absorb,evidence of an intestinal resistance to 1． 25(OH)2D3． J Bone Miner 1991,6(2) :125-132
4． Partitt A.The hyperparathyroidism of chronic renal failure disorder of growth.Kidney Int,1997,52:23
5． perret C,Romaganolo B,et al.Control of nuclear transcription of vitamin D in renalfailure failure implication for medical manage-mant.Kidney Int,1997,52:560-564
6． Laudet V.et al EMBO J,1992,11:1003-1013
7． Lemire J et al.Immunol,1995,134(5) :20-22
8． Provedini M et al.Immunol,1996,136(8) ;27-34
9． Halabe A,Shohat B.Effect of parathyroid adenoma excision on IL-2 and SIL-2R.Metabolism,2000 Teb 49:38-41
10． Goodman WG.Development of adynamic bone in patients with secondary hyperparathroidism after intermittent calcitriol therapy.Kidney Int,1994,46:1160
11． Lewin E,Ladefoged J,Brand L.Parathyrid hormone dependent proliferafion in uremic.Kidney Int 1993,44:379-380
12． Portale A.Pathogeneis of secondary hyperparathyroidism in chronic renal failure Miner electrolyt metab,1997． 17:211-220
13． Coen G.Renal bone disease in 76 patients with varying degrees of predialysis chronjc renal failure a crossing study,nephrol Dial Trans-plant,1996,11:813-819
14． Massry SG.The toxic effects of parathyraid hormone in uremic serum.nephrol,1993,3:306-328
15． 黄岫，李学旺，段林，等．慢性肾衰竭患者血透治疗中细胞免 疫功能的变化及与PTH的关系．肾脏病透析与肾移植杂志，1997，4：116-121
16． Tzammo-Martins,Futata E.Restoration of impaired T-cell prolif-eration after paraphyroidetomy in hemodialysis patients Nephrol 84:224-227 2000
17． 杜学海等．不同投药方式的罗钙全治疗继发性甲旁亢疗效探 讨．肾脏病透析与肾移植杂志，1998，3：230-231
18． Hory B,Racadot E,HitterY,et al.SIL-2R in chronic renal failure.AM J Nephrol,1990,11:276
19． Folcoda N.Decreased 1． 25(OH)2D3 receptor density is associated with a more severe form of parathyroid hyperplasis in chroic uremic patients.J Clin Invest,1993,92:1436
20． 陈士明．急性中毒．第一版，北京：人民卫生出版社，1996，688-669
21． 李汉桐，伍泉．口服炭酸钙对血液透析患者血磷及甲状旁腺激素的影响．中华肾脏病杂志1998，2：14
22． Reichel H.Intermmitent versus continuous administration of 1． 25 (OH)2D3 in expermental renal hyperparathyroidism.Kidney Int,1993,44:1209
23． Helmvt P.The role of the VD endocrine system in health and disease.THE NEW ENGLAND IOVRNAL OF MEDLINE,1999,13:980-981
2． Baylink DJ Calcium and bone homeostasis and changes with aging principle of geriatric medicine.Third Edition.Mcgran-Hill Inc.Pubs chapter 1998,78-87
3． Eastellr Y.Interrelationship among VD metabolism,true calcium absorb,evidence of an intestinal resistance to 1． 25(OH)2D3． J Bone Miner 1991,6(2) :125-132
4． Partitt A.The hyperparathyroidism of chronic renal failure disorder of growth.Kidney Int,1997,52:23
5． perret C,Romaganolo B,et al.Control of nuclear transcription of vitamin D in renalfailure failure implication for medical manage-mant.Kidney Int,1997,52:560-564
6． Laudet V.et al EMBO J,1992,11:1003-1013
7． Lemire J et al.Immunol,1995,134(5) :20-22
8． Provedini M et al.Immunol,1996,136(8) ;27-34
9． Halabe A,Shohat B.Effect of parathyroid adenoma excision on IL-2 and SIL-2R.Metabolism,2000 Teb 49:38-41
10． Goodman WG.Development of adynamic bone in patients with secondary hyperparathroidism after intermittent calcitriol therapy.Kidney Int,1994,46:1160
11． Lewin E,Ladefoged J,Brand L.Parathyrid hormone dependent proliferafion in uremic.Kidney Int 1993,44:379-380
12． Portale A.Pathogeneis of secondary hyperparathyroidism in chronic renal failure Miner electrolyt metab,1997． 17:211-220
13． Coen G.Renal bone disease in 76 patients with varying degrees of predialysis chronjc renal failure a crossing study,nephrol Dial Trans-plant,1996,11:813-819
14． Massry SG.The toxic effects of parathyraid hormone in uremic serum.nephrol,1993,3:306-328
15． 黄岫，李学旺，段林，等．慢性肾衰竭患者血透治疗中细胞免 疫功能的变化及与PTH的关系．肾脏病透析与肾移植杂志，1997，4：116-121
16． Tzammo-Martins,Futata E.Restoration of impaired T-cell prolif-eration after paraphyroidetomy in hemodialysis patients Nephrol 84:224-227 2000
17． 杜学海等．不同投药方式的罗钙全治疗继发性甲旁亢疗效探 讨．肾脏病透析与肾移植杂志，1998，3：230-231
18． Hory B,Racadot E,HitterY,et al.SIL-2R in chronic renal failure.AM J Nephrol,1990,11:276
19． Folcoda N.Decreased 1． 25(OH)2D3 receptor density is associated with a more severe form of parathyroid hyperplasis in chroic uremic patients.J Clin Invest,1993,92:1436
20． 陈士明．急性中毒．第一版，北京：人民卫生出版社，1996，688-669
21． 李汉桐，伍泉．口服炭酸钙对血液透析患者血磷及甲状旁腺激素的影响．中华肾脏病杂志1998，2：14
22． Reichel H.Intermmitent versus continuous administration of 1． 25 (OH)2D3 in expermental renal hyperparathyroidism.Kidney Int,1993,44:1209
23． Helmvt P.The role of the VD endocrine system in health and disease.THE NEW ENGLAND IOVRNAL OF MEDLINE,1999,13:980-981