儿童肾病综合征糖皮质激素受体mRNA表达与糖皮质激素治疗的研究
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摘要
目的：
观察儿童原发性肾病综合征(primary nephrotic syndrome, PNS)治疗过程中糖皮质激素受体(glucocorticoid receptor, GR)亚型GRa、GRβ的mRNA表达水平,探讨GRα和GRβ与儿童PNS的关系。通过GRα和GRβ的mRNA表达变化及各项临床指标的变化来评价三种糖皮质激素(glucocorticoid, GC)类药物对儿童PNS的疗效。
方法：
研究对象为天津市儿童医院2008年11月-2009年10月收治的55例初治PNS患儿,随机分为三组,泼尼松组(A组n=17),曲安西龙组(B组n=20),甲基泼尼松龙组(C组n=18)；以20名儿童为对照。PNS组分别在GC应用0周、4周、8周时取血,通过半定量逆转录-聚合酶链反应(RT-PCR)方法检测外周血单个核细胞(PBMCs)中GRα和GRβ的mRNA表达水平,同时检测PNS组血浆胆固醇(Cho)、血浆白蛋白(Alb)、24小时尿蛋白定量(24hUP)的变化,监测患儿体重、血压、睡眠、饮食等各项临床指标,并记录激素治疗反应,随访转归情况。
结果：
1.GRα和GRβ的mRNA表达水平的变化
1)PNS组和对照组相比GRα和GRβ的mRNA水平变化
a)GC治疗0周时,PNS患儿GRα低于正常儿童,差异有统计学意义(P<0.05)；GRβ高于正常儿童,差异有统计学意义(P<0.05)。
b)PNS患儿GRα表达在GC治疗4周比0周降低,治疗8周比4周升高,差异有统计学意义(P<0.05)；随着GC的治疗,PNS患儿GRβ表达在治疗4周比0周升高,治疗8周比4周升高,差异有统计学意义(P<0.05)。
2)各PNS组GRα和GRβ的mRNA水平的变化
a) GC治疗0周时,A、B、C三组的GRα和GRβ的mRNA水平比较差异无统计学意义(P＞0.05)。
b)GC治疗4周时,A组和B组的GRα比较差异无统计学意义(P＞0.05),C组高于A组和B组,差异有统计学意义(P<0.05)；GC治疗8周,A组和B组的GRα比较差异无统计学意义(P>0.05),C组高于A组和B组,差异有统计学意义(P<0.05)。
c)GC治疗4周时,C组和B组的GRβ比较差异无统计学意义P>0.05)；C组和B组均低于A组,差异有统计学意义(P＜0.05)；GC治疗8周,C组和B组的GRβ比较差异无统计学意义(P>0.05)；C组和B组均低于A组,差异有统计学意义(P<0.05)。
3)PNS患儿GC耐药6例,在GC治疗0、4、8周时,其GRα均低于GC敏感患儿,GRβ均高于GC敏感患儿,差异有统计学意义(P＜0.05)。
2.各项生化指标的变化随着GC治疗,所有PNS患儿的血浆胆固醇均降低；血浆白蛋白上升；24小时尿蛋白定量降低,差异有统计学意义(P<0.05)。
1)Cho：三组PNS组差异无统计学意义(P＞0.05)。
2) Alb:GC治疗4周时,C组和B组比较差异无统计学意义(P＞0.05)；C组和B组均高于A组,差异有统计学意义(P<0.05)；GC治疗8周,C组和B组差异无统计学意义(P>0.05)；C组和B组均高于A组,差异有统计学意义(P＜0.05)。
3) 24hUP:GC治疗4周时和治疗8周时,C组和B组比较差异无统计学意义(P>0.05)；C组和B组均低于A组,差异有统计学意义(P<0.05)。
结论：
1.PNS患儿,PBMCs中GRα和GRβ的mRNA表达存在异常,其表达的紊乱可能是造成GC耐药的原因之一。
2.GC对PNS患儿的治疗,可以调节PBMCs中GRα和GRβ的mRNA表达,不同的GC调节其变化的程度不同,可根据调节水平来评价GC的疗效。
3. RT-PCR方法可应用于临床检测PBMCs中GRα和GRβ的mRNA表达,指导PNS患儿的GC选择,评价治疗效果,预测治疗反应及转归。
4.口服甲基泼尼松龙片可应用于初治PNS患儿的治疗；甲基泼尼松龙,曲安西龙对PNS患儿的治疗疗效优于泼尼松。
Objective:
Observe the mRNA expression levels of GRa and GRB during the treatment of children PNS to explore the relation between GR subtypes and children PNS, thus evaluate the efficacy of three GC drugs through mRNA expression changes of GR subtypes as well as changes of various clinical indicators.
Methods:
The research subjects are 55 PNS kid patients. They are randomly divided into three groups, namely, prednisone group (GroupA=17), triamcinolone group (GroupB=20), methylprednisolone group (GroupC=18) to compare with 20 healthy children. After GC application, collect blood after 0 week,4 weeks and 8 weeks; test the mRNA expression levels of the GR subtypes in PBMCs by semi-quantitative RT-PCR; meanwhile, test changes in the Cho,Alb and 24hUP of PNS children, record the response to hormone therapy and make follow-up prognosis.
Results:
1. Changes in mRNA expression levels of GRa and GRB.
1) Comparison of changes in mRNA expression levels of GRa and GRB between PNS children and healthy children, a) In 0 week of receiving GC treatment, the GRa of PNS children is lower than healthy children (P＜0.05); the GRB of PNS children is higher than healthy children and the difference is statistically significant (P＜0.05).b) After 4 weeks'GC treatment, the GRa of PNS children is lower than that of 0 week (P＜0.05);After 8 weeks' GC treatment, the GRa of PNS children is higher than that of 4 week (P＜0.05).As the treatment time increases, the overall GRβlevel is rising and the difference is statistically significant (P＜0.05).2) Changes of mRNA levels in GRa and GRB of each PNS children group.a) In 0 week of receiving GC treatment, the comparison of changes of mRNA levels in GRa and GRB of the three PNS children groups has no statistical significance (P＞0.05).b) After 4 weeks' and 8 weeks' treatment, the GRa comparison difference between Group A and Group B has no statistical significance (P＞0.05), the GRa of Group C is higher than that of Group A and Group B, the difference is statistically significant (P＜0.05).c) After 4 weeks'and 8 weeks'treatment, the GRB comparison difference of Group B and Group C has no statistical significance (P＞0.05);the GRB of Group B and Group C is lower than that of Group A, the difference is statistically significant (P＜0.05);.3) There are 6 cases of PNS children steroid-resistance; in the treatment of 0,4 and 8 weeks, the GRa of them is lower than steroid-sensitive children and GRB is higher(P＜0.05).
2. Changes in various biochemical indicators:With GC treatment, cho decreases;Alb increases;24hUP decreases and the difference is statistically significant(P＜0.05).
1)Cho:the difference among the three PNS groups has no statistical significance(P＞0.05).2) Alb:after 4 weeks'and 8 weeks'treatment, the comparison difference between Group B and Group C is not statistically significant (P＞0.05); Group C and Group B is higher than Group A(P＜0.05).3)24hUP:after 4 weeks'and 8 weeks' treatment, the comparison difference between Group B and Group C is not statistically significant (P＞0.05),Group C and Group B is lower than Group A(P＜0.05).
Conclusions:
1. Abnormities are found in the mRNA expression of GRa and GRB of PNS children, and the mRNA expression disorder of GRa and GRB of PNS children may be one of the reasons causing GC resistance.
2. GC treatment on PNS children can adjust the mRNA expression of GRa and GRB. Different GC adjustments have different degrees on mRNA expression of GRa and GRB.and the adjusting level can evaluate the efficacy of GC.
3. By semi-quantitative RT-PCR, we can test the mRNA expression levels of the GR subtypes in PBMCs. RT-PCR can be used into clinical test, to evaluate the efficacy of GC drugs and predict the PNS children's treatment effect and prognosis.
4.Oral methylprednisolone can be used in children onset PNS. Methylprednisolone and triamcinolone have a better treatment effect on PNS than that of prednisone.
观察儿童原发性肾病综合征(primary nephrotic syndrome, PNS)治疗过程中糖皮质激素受体(glucocorticoid receptor, GR)亚型GRa、GRβ的mRNA表达水平,探讨GRα和GRβ与儿童PNS的关系。通过GRα和GRβ的mRNA表达变化及各项临床指标的变化来评价三种糖皮质激素(glucocorticoid, GC)类药物对儿童PNS的疗效。
方法：
研究对象为天津市儿童医院2008年11月-2009年10月收治的55例初治PNS患儿,随机分为三组,泼尼松组(A组n=17),曲安西龙组(B组n=20),甲基泼尼松龙组(C组n=18)；以20名儿童为对照。PNS组分别在GC应用0周、4周、8周时取血,通过半定量逆转录-聚合酶链反应(RT-PCR)方法检测外周血单个核细胞(PBMCs)中GRα和GRβ的mRNA表达水平,同时检测PNS组血浆胆固醇(Cho)、血浆白蛋白(Alb)、24小时尿蛋白定量(24hUP)的变化,监测患儿体重、血压、睡眠、饮食等各项临床指标,并记录激素治疗反应,随访转归情况。
结果：
1.GRα和GRβ的mRNA表达水平的变化
1)PNS组和对照组相比GRα和GRβ的mRNA水平变化
a)GC治疗0周时,PNS患儿GRα低于正常儿童,差异有统计学意义(P<0.05)；GRβ高于正常儿童,差异有统计学意义(P<0.05)。
b)PNS患儿GRα表达在GC治疗4周比0周降低,治疗8周比4周升高,差异有统计学意义(P<0.05)；随着GC的治疗,PNS患儿GRβ表达在治疗4周比0周升高,治疗8周比4周升高,差异有统计学意义(P<0.05)。
2)各PNS组GRα和GRβ的mRNA水平的变化
a) GC治疗0周时,A、B、C三组的GRα和GRβ的mRNA水平比较差异无统计学意义(P＞0.05)。
b)GC治疗4周时,A组和B组的GRα比较差异无统计学意义(P＞0.05),C组高于A组和B组,差异有统计学意义(P<0.05)；GC治疗8周,A组和B组的GRα比较差异无统计学意义(P>0.05),C组高于A组和B组,差异有统计学意义(P<0.05)。
c)GC治疗4周时,C组和B组的GRβ比较差异无统计学意义P>0.05)；C组和B组均低于A组,差异有统计学意义(P＜0.05)；GC治疗8周,C组和B组的GRβ比较差异无统计学意义(P>0.05)；C组和B组均低于A组,差异有统计学意义(P<0.05)。
3)PNS患儿GC耐药6例,在GC治疗0、4、8周时,其GRα均低于GC敏感患儿,GRβ均高于GC敏感患儿,差异有统计学意义(P＜0.05)。
2.各项生化指标的变化随着GC治疗,所有PNS患儿的血浆胆固醇均降低；血浆白蛋白上升；24小时尿蛋白定量降低,差异有统计学意义(P<0.05)。
1)Cho：三组PNS组差异无统计学意义(P＞0.05)。
2) Alb:GC治疗4周时,C组和B组比较差异无统计学意义(P＞0.05)；C组和B组均高于A组,差异有统计学意义(P<0.05)；GC治疗8周,C组和B组差异无统计学意义(P>0.05)；C组和B组均高于A组,差异有统计学意义(P＜0.05)。
3) 24hUP:GC治疗4周时和治疗8周时,C组和B组比较差异无统计学意义(P>0.05)；C组和B组均低于A组,差异有统计学意义(P<0.05)。
结论：
1.PNS患儿,PBMCs中GRα和GRβ的mRNA表达存在异常,其表达的紊乱可能是造成GC耐药的原因之一。
2.GC对PNS患儿的治疗,可以调节PBMCs中GRα和GRβ的mRNA表达,不同的GC调节其变化的程度不同,可根据调节水平来评价GC的疗效。
3. RT-PCR方法可应用于临床检测PBMCs中GRα和GRβ的mRNA表达,指导PNS患儿的GC选择,评价治疗效果,预测治疗反应及转归。
4.口服甲基泼尼松龙片可应用于初治PNS患儿的治疗；甲基泼尼松龙,曲安西龙对PNS患儿的治疗疗效优于泼尼松。
Objective:
Observe the mRNA expression levels of GRa and GRB during the treatment of children PNS to explore the relation between GR subtypes and children PNS, thus evaluate the efficacy of three GC drugs through mRNA expression changes of GR subtypes as well as changes of various clinical indicators.
Methods:
The research subjects are 55 PNS kid patients. They are randomly divided into three groups, namely, prednisone group (GroupA=17), triamcinolone group (GroupB=20), methylprednisolone group (GroupC=18) to compare with 20 healthy children. After GC application, collect blood after 0 week,4 weeks and 8 weeks; test the mRNA expression levels of the GR subtypes in PBMCs by semi-quantitative RT-PCR; meanwhile, test changes in the Cho,Alb and 24hUP of PNS children, record the response to hormone therapy and make follow-up prognosis.
Results:
1. Changes in mRNA expression levels of GRa and GRB.
1) Comparison of changes in mRNA expression levels of GRa and GRB between PNS children and healthy children, a) In 0 week of receiving GC treatment, the GRa of PNS children is lower than healthy children (P＜0.05); the GRB of PNS children is higher than healthy children and the difference is statistically significant (P＜0.05).b) After 4 weeks'GC treatment, the GRa of PNS children is lower than that of 0 week (P＜0.05);After 8 weeks' GC treatment, the GRa of PNS children is higher than that of 4 week (P＜0.05).As the treatment time increases, the overall GRβlevel is rising and the difference is statistically significant (P＜0.05).2) Changes of mRNA levels in GRa and GRB of each PNS children group.a) In 0 week of receiving GC treatment, the comparison of changes of mRNA levels in GRa and GRB of the three PNS children groups has no statistical significance (P＞0.05).b) After 4 weeks' and 8 weeks' treatment, the GRa comparison difference between Group A and Group B has no statistical significance (P＞0.05), the GRa of Group C is higher than that of Group A and Group B, the difference is statistically significant (P＜0.05).c) After 4 weeks'and 8 weeks'treatment, the GRB comparison difference of Group B and Group C has no statistical significance (P＞0.05);the GRB of Group B and Group C is lower than that of Group A, the difference is statistically significant (P＜0.05);.3) There are 6 cases of PNS children steroid-resistance; in the treatment of 0,4 and 8 weeks, the GRa of them is lower than steroid-sensitive children and GRB is higher(P＜0.05).
2. Changes in various biochemical indicators:With GC treatment, cho decreases;Alb increases;24hUP decreases and the difference is statistically significant(P＜0.05).
1)Cho:the difference among the three PNS groups has no statistical significance(P＞0.05).2) Alb:after 4 weeks'and 8 weeks'treatment, the comparison difference between Group B and Group C is not statistically significant (P＞0.05); Group C and Group B is higher than Group A(P＜0.05).3)24hUP:after 4 weeks'and 8 weeks' treatment, the comparison difference between Group B and Group C is not statistically significant (P＞0.05),Group C and Group B is lower than Group A(P＜0.05).
Conclusions:
1. Abnormities are found in the mRNA expression of GRa and GRB of PNS children, and the mRNA expression disorder of GRa and GRB of PNS children may be one of the reasons causing GC resistance.
2. GC treatment on PNS children can adjust the mRNA expression of GRa and GRB. Different GC adjustments have different degrees on mRNA expression of GRa and GRB.and the adjusting level can evaluate the efficacy of GC.
3. By semi-quantitative RT-PCR, we can test the mRNA expression levels of the GR subtypes in PBMCs. RT-PCR can be used into clinical test, to evaluate the efficacy of GC drugs and predict the PNS children's treatment effect and prognosis.
4.Oral methylprednisolone can be used in children onset PNS. Methylprednisolone and triamcinolone have a better treatment effect on PNS than that of prednisone.
引文
[1]Eddy AA, Symons JM. Nephrotic syndrome in childhood[J]. Lanct,2003,362 (9384):629-639.
[2]Wong W.Idiopathic nephrotic syndrome in New Zealand chindren, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance-study [J]. J Pedia Child Health,2007, 43(2007):337-341.
[3]杨霁云,白克敏主编.小儿肾脏病基础与临床[M].第一版.北京：人民卫生出版社,2000：154.
[4]何庆南,易著文,何小解,等.肾病综合征患儿外周血单个核细胞内GRa和GRβ表达的意义[J].中华儿科杂志,2001,39(7)：406-410.
[5]何庆南,易著文,何小解,等.GRβ在肾病综合征患儿中的表达及影响因素研究[J].中国病理生理杂志,2002,18(9)：1042-1045.
[6]Cohen SL, Halass JL, Friedman JM, et al. Human leptin characterization [J]. Nature,1996,382(6592):589.
[7]周太光,王峥,夏彦等.雷公腾多甙对肾病综合征患儿糖皮质激素受体的影响及其临床意义[J].临床儿科杂志,2003,21(10)：612-614.
[8]王小寒.甲泼尼龙片在原发性肾病综合征中的临床应用[J].中华全科医学,2008,6(7)：696-697.
[9]郭立申,骆纯才,康国贵等.曲安西龙治疗原发性肾病综合征疗效观察[J].中华儿科杂志,2001,39(12)：750.
[10]常克,钟柏松.阿赛松治疗肾病综合征疗效观察[J].成都医药,2001,27(1)52-53.
[11]林珊,屈会起,江建青等.阿赛松对肾病综合征治疗作用的随机对照研究[J].天津医药,2000,28(7)432-433.
[12]李琳芸,王柳燕综述,王昌富审校.糖皮质激素受体及其检测方法的研究进展[J].微循环学杂志,2005,15(3)：68-71.
[13]中华医学会儿科学分会肾脏病学组.儿童常见肾脏疾病诊治偱证指南(一)：激素敏感、复发／依赖肾病综合征诊治循证指南(试行)[J].中华儿科杂志,2009,47(3)：167-170.
[14]中华医学会儿科学分会肾脏病学组.小儿肾小球疾病的临床分类、诊断及治疗[J].中华儿科杂志,2001,39(12)：746-749.
[15]Behrman RE. Nelson textbook of pediatrics,16th [M]. Philadelphia:W B Sauders Company,2001:1500-1502.
[16]胡学强楼之茵周国钰.多发性硬化患者糖皮质激素受体蛋白和mRNA表达与激素疗效的相关性[J].中华神经科杂志,2007,40(9)605-609.
[17]Filler G, Young E, Geier P, et al. Is there really an increase in non-minimal change nephrotic syndrome in chinaren[J]. Am J Kidney Dis,2003,42(6):1107-1113.
[18]Arbus GS, Poucell S, Bacheyie GS, et al. Focal segmental glomerul osclerosis with idiopathic nephrotic syndrome:three types of clinical response[J]. J Pediatr, 1982,101 (1):40-45.
[19]A Report of the International Study of Kidney Disease in Children:Nephrotic syndrome in children:prediction of histopathology from clinical and laboratory characteristics at time of diagnosis [J]. Kidney International,1978,13 (1978):159-165.
[20]Barratt TM, Clark AG. Steroid-responsive nephrotic syndrome.In:Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology.4th [M]. Baltimore: Lippincott/Williams&Wilkins,1999,13:731-746.
[21]Schwartz MM, Korbet SM. Primary focal segmental glomerulosclerosis: pathology, histological variants, and pathogenesis [J]. Am J Kidney Dis,1993,22 (6):874-883.
[22]Korbet SM, Schwartz MM, Lewis EJ. Primary focal segmental glomerulosclerosis:clinical course and response to therapy [J]. Am J Kidney Dis 1994,23(6):773-783.
[23]Haack D, Scharer K, Asam-Tauscher A, et al. Glucocorticoid receptors in idiopathic nephrotic syndrome [J]. Pediatr Nephro,1999,13 (8):653-656.
[24]Pujols L, Mull J, Perez M, et al. Expression of the human glucocorticoid receptor alph and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone[J].Am J Respir Cell Mol Biol,2001, 24(1):49-57.
[25]Lewis-Tuffin LJ, Cidlowski JA. The physiology of human glucocorticoid receptor β (hGR β) and glucocorticoid resistance[J].Ann N Y Aead Sci, 2006,1069:1-9.
[26]叶建伟,丁洁,黄建萍等.糖皮质激素受体基因多态性与肾病综合征患儿激素耐药相关性探讨[J].中华儿科杂志,2003,41(9)：661-665.
[27]Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children (remew)[J]. Cochrane Database Syst Rev,2007(4), CD001553.
[28]Matthew R;Yudtl and John A,Cidlowski. The Glucocorticoid Receptor:Coding a Diversity of Proteins and Responses through a Single Gene[J]. Molecular Endocrinology,2002,16(8):1719-1726.
[29]Krett NL, Pillay S, Moalli PA, et al. Avariant glucocorticoid receptor messenger RNA is expressedin multiple myeloma patients [J]. Cancer Res,1995,55(13):2727-2729.
[30]Rivers C, Levy A, Hancock J, et al. Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of lterrmtivesplicing[J]. J Clin Endocrinol Metab,1999,84(11):4283-4286.
[31]Buttgereit F, Wehling M, Burmester GR. A new hypothesis of modular glucocorticoid actions:steroid treatment of rheumatic disease revisited [J]. Arthritis Rheum,1998,41(5):761-767.
[32]杜臻,唐福林.糖皮质激素抗炎作用机制的研究进展[J].中华医学杂志,2006,86(35)：2512-2515.
[33]Hollenberg SM, Weinberger C, Ong ES, et al. Primary structure and expression of a functional human glucocorticoid receptor Cdna[J]. Nature,1985, 318(6047):635-641.
[34]Bamberger CM, Bamberger A, de Castro M, et al. Glucocorticoid receptor B, a potential endogenous inhibitor of glucocorticoid action in humans[J].J Clin Invest,1995,95(6):2435-2441.
[35]Yudt MR, Jewell CM, Bienstock RJ, et al. Molecular origins for the dominant negative function of human glucocorticoid receptor beta[J].Mol Cell Boil 2003, 23(12):4319-4330.
[36]Rhen T, Cidlowski JA.Anti inflammatory action of glucocorticoids-new mechanisms for old drugs [J].N End J Med,2005,353(16):1711-1723.
[37]Oakly RH, Webster JC, Sar M, et al. Expression and subcellular distribution of the 13-isoform of the human glucocorticoid receptor [J].Endocrinology,1997, 138(11):5028-5038.
[38]Cho YJ, Lee KE. Decreased glucocorticoid binding affinity to glucocorticoid receptor is important in the poor response to steroid therapy of older-aged patients with severe bronchial asthma [J]. Allergy Asthma Proc,2003,24(5): 353-358.
[39]Pujols L, Xaubet A, Ramirez J, et al. Expression of glucocorticoid receptors alpha and beta in steroid sensitive and steroid insensitive interstitial lung disease[J]. Thorax,2004.59(8):687-693.
[40]Honda M, Orii F, Ayabe T, et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis[J]. Gastroent erology,2000.118(5):859-866.
[41]Oakley RH, Jewell CM, Yudt MR, et al. The dominant negative activity of the human glucocorticoid receptor beta isoform. Specificity and mechanisms of actio[J]. J Binl Chem,1999.274:27857-27866.
[42]Matalon A, Valeri A, Appel GB.Treatment of Focal segmental Glomerulosclerosis [J].Seminars in Nephrology.2000,20 (3):309-317.
[43]Rydel J T, Kor bet Sm, Borok RI.et al:Focal segmental glomerular sclerosis in adults:pressentation, Course and reponse to treatment [J].Am J Kidney Dis, 1995,25(4):534-542.
[44]万瑞香,隋忠国,李自普主编.新编儿科药物学[M].第二版.北京：人民卫生出版社,2004：317-323.
[45]Imbasciali E, Guamano R, Edefonti A, et al. Controlled trial of methylprednisolone pulses and low dose oral prenisone for the minimal change nephrotic syndrome[J]. Br Med J (Clin Res Ed),1985,291(6505):1305-1308.
[46]张焱,黄建萍,丁洁等.甲基泼尼松龙冲击疗法治疗小儿肾病综合征复发疗效观察[J].临床儿科杂志,2007,25(4)：274-277.
[47]Oren Fruchter,Tomoshige Kino,Emmanouil Zoumakis,et al.The human glucocorticoid receptor(GR) isoform B differentially suppresses GRα-Induced Transactivation Stimulated by Synthetic Glucocorticoids [J]. The Journal of Clinical Endocrinology & Metabolism,2005,90(6):3505-3509.
[48]Dario Marchetti, Nguyen T, Van Bahiru.Flow cytometric analysis of glucocorticoid receptor using monocional antibody and fluoresceinated ligand probes [J].Cancer Research,1989,49(4):863-869.
[49]Pojuls L, Mul J, Roca-Ferrer J. Expression of glucocorticoid receptor alpha and beta isoforms in human cells and tissues [J]. Am J Physiol Cell Physiol,2002, 283(4):C1 324-C1 331.
[50]余松林主编.医学统计学[M].北京：人民卫生出版社.2002：422-341.
[51]万霞,刘建平.临床试验中的随机分组方法[J].中医杂志.2007,48(3)216-219.
[52]Xu RB, Liu ZM, Zhao Y. A study on the circadian rhythm of glucocorticoid receptor [J].Neuroendocrinology,1991,53, (suppl 1):31-36.
[53]Yao Z, Dubois DC, Almon RR,et al. Modeling Circadian Rhythms of Glucocorticoid Receptor and Glutamine Synthetase Expression in Rat Skeletal Muscle[J]. Pharmaceutical Research,2006,23(4):670-679.
[54]翁端怡,曾章超,郑健.肾康灵冲剂治疗小儿肾炎性肾病综合征临床探析[J].中国中西医结合肾病杂志.2005,6(9)：543-545.
[55]Ashwell JD, Lu FW, Vacchio MS. Glucocorticoids in T cell development and function [J]. Annu Rev Immunol,2000,18:309-345.
[56]Mocan H, Erduran E, Karaguzel G. High dose methyprednisolone therapy in nephrotic syndrome [J]. I ndian J Pediatr,1999,66 (2):171-174.
[57]熊晓玲,贾汝汉.甲基强的松龙治疗原发性肾病综合征的临床观察[J].Journal of Chinese Physician,2006,8(1):124-125.
[1]Smoak KA, Cidlowski JA. Mechanisms of glucocorticoid receptor signaling during inflammation[J]. Mech Ageing Dev,2004,125(10-11):697-706.
[2]Lu NZ, Cidlowski JA. The origin and functions of multiple human glucocorticoid receptor isoforms[J]. Ann N Y Acad Sci,2004(1024):102-123.
[3]Breslin MB,Geng CD,Vedeckis WV. Multiple promotersexist in the human GR gene, one of which isactivatedby glucocorticoids[J]. Mol Endocrinol,2001, 15(8):1381-1395.
[4]Matthew R, Yudt, John A. Cidlowski. The Glucocorticoid Receptor:Coding a Diversity of Proteins and Responses through a Single Gene [J]. Molecular Endocrinology,2002,16(8):1719-1726.
[5]Krett NL, Pillay S, Moalli PA,et al. Avariant glucocorticoid receptor messenger RNA is expressedin multiple myeloma patients[J]. Cancer Res,1995,55(13): 2727-2729.
[6]Rivers C, Levy A, Hancock J, et al. Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alterrmtivesplicing[J]. J Clin Endocrinol Metab,1999,84(11):4283-4286.
[7]Rhen T, Cidlowski JA.Antiinflammatory action of glucocortcoids new mechanisms for old drugs [J].N End J Med,2005,353(16):1711-1723.
[8]Pojuls L, Mul J, Roca-Ferrer J. Expression of glucocorticoid receptor alpha and beta isoforms in human cells and tissues [J]. Am J Physiol Cell Physiol,2002, 283(4):C1 324-C1 331.
[9]RH DeRijk, M Schaaf, ER De Kloet. Glucocorticoid receptor variants:clinical implications [J]. Jounal of Steriod Biochemistry and Molecular Biology,2002, 81(2):103-122.
[10]Honda M, Orii F, Ayabe T, et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis[J]. Gastroenterology,2000,118 (5):859-866.
[11]Christodoulopoulos P, Leung DYM, Elliott MW, et al. Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma [J]. J Allergy Clin Immunol,2000,106(3):479-484.
[12]Schasf MJ, Cidlowski JA.Molecular mechanisms of glucocorticoid action and resistance [J].J Streoid Biochem Mol Biol,2003,83(1-5):37-48.
[13]Buttgereit F, Wehling M, Burmester GR.A new hypothesis of modular glucocorticoid actions:steroid treatment of rhenmatic disease revisited [J]. Arthritis Rheum,1998,41(5):761-767.
[14]Bray PJ, Cotton RG. Variations of the human glucocorticoid receptor geng (NR3C1):pathological and in vitro mutations and olymorphisms [J]. Hum Mutat,2003,21 (6):557-568.
[15]叶建伟,丁洁,黄建萍等.糖皮质激素受体基因多态性与肾病综合征患儿激素耐药相关性探讨[J].中华儿科杂志,2003,41(9)：661-665.
[16]Koper JW,Stolk RP,de Lange P,et al.Lack of association between five polymorphisms in the human glucocorticoid receptor gene and lucocorticoid resistance[J].Hum Genet,1997,99(5):663-668.
[17]Antonini SR, Latronico AC,Elias LL,et al. Glucocorticoid receptor gene polymorphisms in ACTH-secreting pituitary tumours[J]. Clin Endorcrinol (Oxf). 2002,57(5):657-662.
[18]de Lange P, Koper JW,Huizenga NA,et al. Differential hormone-dependent transcriptional actibation and-repression by naaturally occurring hunman glucocorticoid receptor variants[J].Mol Endocrinol,1997,11(8):1156-1164.
[19]Hillmann AG, Ramdas J,Multanen K,et al.Glucocorticoid receptor gene mutations in leukemic cells acquired in vitro and in vivo[J]. Cancer Res,2000, 60(7):2056-2062.
[20]Parks LL, Tumey MK, Detera-Wadleigh S,et al. An ACTH-producing small cell lung cancer expresses aberrant glucocorticoid receptor transcripts from anormal gene [J], Mol Cell Endocrino,1998,142(1-2):175-181.
[21]Longui CA,Vottero A,Adamsom PC,et al.Low glucocorticoid receptor alpha/beta ratio in T-cell lutmphoblastic leckemia[J].Horm Metab Res,2000, 32(10):401-406.
[22]Yudt MR, Jewell CM, Bienstock RJ, et al. Molcular origins for the dominant negative function of human glucocorticoid receptor beta[J].Mol Cell Boil 23(12):4319-4330.
[23]Pujols L, Mull J, Roca-Ferer J, et al. Expression of the human glucocorticoid receptor alpha and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone[J].Am Jrespir Cell MolBiol,2001,24(1):49-57.
[24]Lewis-Tuffin LJ, Cidlowski JA.The Physiology of human glucocorticoid receptorβ(hGRβ) and glucocorticoid resistance[J].Ann N Y Aead Sci,2006, 1069:1-9.
[25]Hamilos DL, Leung DY, Muro S, et al.Grbeta expression in nasal polyp inflammatory cells and its relaationship to the anti-inflammatory effects of intranasal fluticasone[J].J Allergy Clin Immunol,2001,108(1):59-68.
[26]Leung DY, Hamid Q, Vottero A, et al. Association of glucocorticoid in sensitivity with increased expression of glucocorticoid receptor beta[J].J The Journal of Experimental Medical,1997,186(3):1567-1574.
[27]Koga Y, Matsuzaki A, Suminoe A, et al.Differential mRNA expression of glucocortcoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphobastic leukemia in children[J].Pediatr Blood Cancer,2005,45(2):121-127.
[28]Lane SJ, Lee TH.Mechanisms of corticosteroid resistance in asthmastic patients [J].Int Arch Allergy Immunol,1997,113(1-3):193-195.
[29]Bailey S, Hall AG, Pearson AD, et al.Glucocorticoid resistance and the AP-1 transcription factor in leukaemia [J].Adv Exp Med Biol,1999,457:615-627.
[30]Liu DH,Su YP,Zhang W,et al.Changes in glucocorticoid and mineralocorticoid receptors of liver and Kinney cytosols after pathologic stress and its regulation in rats[J],Crit Care Med,2002,30(3):623-627.
[31]Miller AH, Pariante CM, Pearce BD.Effects of cytokines on glucocorticoid receptor expression and fuction. Glucocorticoid resistance and relevance to depression [J].Adv Exp Med Biol,1999,461:107-116.
[32]Biola A, Lefebvre P, P errin-Wolff M, et al. Interleukin-2 inhibits glucocorticoid receptor transcriptional activity through a mechanism involving STATS (signal transducer and activator of transcription 5) but not Ap-1[J]. Mol Endocrinol, 2001,15(7):1062-1076.
[33]周太光,王铮,夏彦等.雷公藤多甙对肾病综合征患儿糖皮质激素受体的影响及其临床意义[J].临床儿科杂志,2003,21(10)：612-614.
[34]杜娟,凌昌全,陈永安等.淫羊藿和熟地煎剂对糖皮质激素受体下调模型大鼠糖皮质激素受体的影响[J].中国中西医结合杂志,2003,28(1)：64-67.
[35]翁端怡,曾章超,郑健.肾康灵冲剂治疗小儿肾炎性肾病综合征临床探析[J].中国中西医结合肾病杂志.2005,6(9)：543-545.
[2]Wong W.Idiopathic nephrotic syndrome in New Zealand chindren, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance-study [J]. J Pedia Child Health,2007, 43(2007):337-341.
[3]杨霁云,白克敏主编.小儿肾脏病基础与临床[M].第一版.北京：人民卫生出版社,2000：154.
[4]何庆南,易著文,何小解,等.肾病综合征患儿外周血单个核细胞内GRa和GRβ表达的意义[J].中华儿科杂志,2001,39(7)：406-410.
[5]何庆南,易著文,何小解,等.GRβ在肾病综合征患儿中的表达及影响因素研究[J].中国病理生理杂志,2002,18(9)：1042-1045.
[6]Cohen SL, Halass JL, Friedman JM, et al. Human leptin characterization [J]. Nature,1996,382(6592):589.
[7]周太光,王峥,夏彦等.雷公腾多甙对肾病综合征患儿糖皮质激素受体的影响及其临床意义[J].临床儿科杂志,2003,21(10)：612-614.
[8]王小寒.甲泼尼龙片在原发性肾病综合征中的临床应用[J].中华全科医学,2008,6(7)：696-697.
[9]郭立申,骆纯才,康国贵等.曲安西龙治疗原发性肾病综合征疗效观察[J].中华儿科杂志,2001,39(12)：750.
[10]常克,钟柏松.阿赛松治疗肾病综合征疗效观察[J].成都医药,2001,27(1)52-53.
[11]林珊,屈会起,江建青等.阿赛松对肾病综合征治疗作用的随机对照研究[J].天津医药,2000,28(7)432-433.
[12]李琳芸,王柳燕综述,王昌富审校.糖皮质激素受体及其检测方法的研究进展[J].微循环学杂志,2005,15(3)：68-71.
[13]中华医学会儿科学分会肾脏病学组.儿童常见肾脏疾病诊治偱证指南(一)：激素敏感、复发／依赖肾病综合征诊治循证指南(试行)[J].中华儿科杂志,2009,47(3)：167-170.
[14]中华医学会儿科学分会肾脏病学组.小儿肾小球疾病的临床分类、诊断及治疗[J].中华儿科杂志,2001,39(12)：746-749.
[15]Behrman RE. Nelson textbook of pediatrics,16th [M]. Philadelphia:W B Sauders Company,2001:1500-1502.
[16]胡学强楼之茵周国钰.多发性硬化患者糖皮质激素受体蛋白和mRNA表达与激素疗效的相关性[J].中华神经科杂志,2007,40(9)605-609.
[17]Filler G, Young E, Geier P, et al. Is there really an increase in non-minimal change nephrotic syndrome in chinaren[J]. Am J Kidney Dis,2003,42(6):1107-1113.
[18]Arbus GS, Poucell S, Bacheyie GS, et al. Focal segmental glomerul osclerosis with idiopathic nephrotic syndrome:three types of clinical response[J]. J Pediatr, 1982,101 (1):40-45.
[19]A Report of the International Study of Kidney Disease in Children:Nephrotic syndrome in children:prediction of histopathology from clinical and laboratory characteristics at time of diagnosis [J]. Kidney International,1978,13 (1978):159-165.
[20]Barratt TM, Clark AG. Steroid-responsive nephrotic syndrome.In:Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology.4th [M]. Baltimore: Lippincott/Williams&Wilkins,1999,13:731-746.
[21]Schwartz MM, Korbet SM. Primary focal segmental glomerulosclerosis: pathology, histological variants, and pathogenesis [J]. Am J Kidney Dis,1993,22 (6):874-883.
[22]Korbet SM, Schwartz MM, Lewis EJ. Primary focal segmental glomerulosclerosis:clinical course and response to therapy [J]. Am J Kidney Dis 1994,23(6):773-783.
[23]Haack D, Scharer K, Asam-Tauscher A, et al. Glucocorticoid receptors in idiopathic nephrotic syndrome [J]. Pediatr Nephro,1999,13 (8):653-656.
[24]Pujols L, Mull J, Perez M, et al. Expression of the human glucocorticoid receptor alph and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone[J].Am J Respir Cell Mol Biol,2001, 24(1):49-57.
[25]Lewis-Tuffin LJ, Cidlowski JA. The physiology of human glucocorticoid receptor β (hGR β) and glucocorticoid resistance[J].Ann N Y Aead Sci, 2006,1069:1-9.
[26]叶建伟,丁洁,黄建萍等.糖皮质激素受体基因多态性与肾病综合征患儿激素耐药相关性探讨[J].中华儿科杂志,2003,41(9)：661-665.
[27]Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children (remew)[J]. Cochrane Database Syst Rev,2007(4), CD001553.
[28]Matthew R;Yudtl and John A,Cidlowski. The Glucocorticoid Receptor:Coding a Diversity of Proteins and Responses through a Single Gene[J]. Molecular Endocrinology,2002,16(8):1719-1726.
[29]Krett NL, Pillay S, Moalli PA, et al. Avariant glucocorticoid receptor messenger RNA is expressedin multiple myeloma patients [J]. Cancer Res,1995,55(13):2727-2729.
[30]Rivers C, Levy A, Hancock J, et al. Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of lterrmtivesplicing[J]. J Clin Endocrinol Metab,1999,84(11):4283-4286.
[31]Buttgereit F, Wehling M, Burmester GR. A new hypothesis of modular glucocorticoid actions:steroid treatment of rheumatic disease revisited [J]. Arthritis Rheum,1998,41(5):761-767.
[32]杜臻,唐福林.糖皮质激素抗炎作用机制的研究进展[J].中华医学杂志,2006,86(35)：2512-2515.
[33]Hollenberg SM, Weinberger C, Ong ES, et al. Primary structure and expression of a functional human glucocorticoid receptor Cdna[J]. Nature,1985, 318(6047):635-641.
[34]Bamberger CM, Bamberger A, de Castro M, et al. Glucocorticoid receptor B, a potential endogenous inhibitor of glucocorticoid action in humans[J].J Clin Invest,1995,95(6):2435-2441.
[35]Yudt MR, Jewell CM, Bienstock RJ, et al. Molecular origins for the dominant negative function of human glucocorticoid receptor beta[J].Mol Cell Boil 2003, 23(12):4319-4330.
[36]Rhen T, Cidlowski JA.Anti inflammatory action of glucocorticoids-new mechanisms for old drugs [J].N End J Med,2005,353(16):1711-1723.
[37]Oakly RH, Webster JC, Sar M, et al. Expression and subcellular distribution of the 13-isoform of the human glucocorticoid receptor [J].Endocrinology,1997, 138(11):5028-5038.
[38]Cho YJ, Lee KE. Decreased glucocorticoid binding affinity to glucocorticoid receptor is important in the poor response to steroid therapy of older-aged patients with severe bronchial asthma [J]. Allergy Asthma Proc,2003,24(5): 353-358.
[39]Pujols L, Xaubet A, Ramirez J, et al. Expression of glucocorticoid receptors alpha and beta in steroid sensitive and steroid insensitive interstitial lung disease[J]. Thorax,2004.59(8):687-693.
[40]Honda M, Orii F, Ayabe T, et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis[J]. Gastroent erology,2000.118(5):859-866.
[41]Oakley RH, Jewell CM, Yudt MR, et al. The dominant negative activity of the human glucocorticoid receptor beta isoform. Specificity and mechanisms of actio[J]. J Binl Chem,1999.274:27857-27866.
[42]Matalon A, Valeri A, Appel GB.Treatment of Focal segmental Glomerulosclerosis [J].Seminars in Nephrology.2000,20 (3):309-317.
[43]Rydel J T, Kor bet Sm, Borok RI.et al:Focal segmental glomerular sclerosis in adults:pressentation, Course and reponse to treatment [J].Am J Kidney Dis, 1995,25(4):534-542.
[44]万瑞香,隋忠国,李自普主编.新编儿科药物学[M].第二版.北京：人民卫生出版社,2004：317-323.
[45]Imbasciali E, Guamano R, Edefonti A, et al. Controlled trial of methylprednisolone pulses and low dose oral prenisone for the minimal change nephrotic syndrome[J]. Br Med J (Clin Res Ed),1985,291(6505):1305-1308.
[46]张焱,黄建萍,丁洁等.甲基泼尼松龙冲击疗法治疗小儿肾病综合征复发疗效观察[J].临床儿科杂志,2007,25(4)：274-277.
[47]Oren Fruchter,Tomoshige Kino,Emmanouil Zoumakis,et al.The human glucocorticoid receptor(GR) isoform B differentially suppresses GRα-Induced Transactivation Stimulated by Synthetic Glucocorticoids [J]. The Journal of Clinical Endocrinology & Metabolism,2005,90(6):3505-3509.
[48]Dario Marchetti, Nguyen T, Van Bahiru.Flow cytometric analysis of glucocorticoid receptor using monocional antibody and fluoresceinated ligand probes [J].Cancer Research,1989,49(4):863-869.
[49]Pojuls L, Mul J, Roca-Ferrer J. Expression of glucocorticoid receptor alpha and beta isoforms in human cells and tissues [J]. Am J Physiol Cell Physiol,2002, 283(4):C1 324-C1 331.
[50]余松林主编.医学统计学[M].北京：人民卫生出版社.2002：422-341.
[51]万霞,刘建平.临床试验中的随机分组方法[J].中医杂志.2007,48(3)216-219.
[52]Xu RB, Liu ZM, Zhao Y. A study on the circadian rhythm of glucocorticoid receptor [J].Neuroendocrinology,1991,53, (suppl 1):31-36.
[53]Yao Z, Dubois DC, Almon RR,et al. Modeling Circadian Rhythms of Glucocorticoid Receptor and Glutamine Synthetase Expression in Rat Skeletal Muscle[J]. Pharmaceutical Research,2006,23(4):670-679.
[54]翁端怡,曾章超,郑健.肾康灵冲剂治疗小儿肾炎性肾病综合征临床探析[J].中国中西医结合肾病杂志.2005,6(9)：543-545.
[55]Ashwell JD, Lu FW, Vacchio MS. Glucocorticoids in T cell development and function [J]. Annu Rev Immunol,2000,18:309-345.
[56]Mocan H, Erduran E, Karaguzel G. High dose methyprednisolone therapy in nephrotic syndrome [J]. I ndian J Pediatr,1999,66 (2):171-174.
[57]熊晓玲,贾汝汉.甲基强的松龙治疗原发性肾病综合征的临床观察[J].Journal of Chinese Physician,2006,8(1):124-125.
[1]Smoak KA, Cidlowski JA. Mechanisms of glucocorticoid receptor signaling during inflammation[J]. Mech Ageing Dev,2004,125(10-11):697-706.
[2]Lu NZ, Cidlowski JA. The origin and functions of multiple human glucocorticoid receptor isoforms[J]. Ann N Y Acad Sci,2004(1024):102-123.
[3]Breslin MB,Geng CD,Vedeckis WV. Multiple promotersexist in the human GR gene, one of which isactivatedby glucocorticoids[J]. Mol Endocrinol,2001, 15(8):1381-1395.
[4]Matthew R, Yudt, John A. Cidlowski. The Glucocorticoid Receptor:Coding a Diversity of Proteins and Responses through a Single Gene [J]. Molecular Endocrinology,2002,16(8):1719-1726.
[5]Krett NL, Pillay S, Moalli PA,et al. Avariant glucocorticoid receptor messenger RNA is expressedin multiple myeloma patients[J]. Cancer Res,1995,55(13): 2727-2729.
[6]Rivers C, Levy A, Hancock J, et al. Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alterrmtivesplicing[J]. J Clin Endocrinol Metab,1999,84(11):4283-4286.
[7]Rhen T, Cidlowski JA.Antiinflammatory action of glucocortcoids new mechanisms for old drugs [J].N End J Med,2005,353(16):1711-1723.
[8]Pojuls L, Mul J, Roca-Ferrer J. Expression of glucocorticoid receptor alpha and beta isoforms in human cells and tissues [J]. Am J Physiol Cell Physiol,2002, 283(4):C1 324-C1 331.
[9]RH DeRijk, M Schaaf, ER De Kloet. Glucocorticoid receptor variants:clinical implications [J]. Jounal of Steriod Biochemistry and Molecular Biology,2002, 81(2):103-122.
[10]Honda M, Orii F, Ayabe T, et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis[J]. Gastroenterology,2000,118 (5):859-866.
[11]Christodoulopoulos P, Leung DYM, Elliott MW, et al. Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma [J]. J Allergy Clin Immunol,2000,106(3):479-484.
[12]Schasf MJ, Cidlowski JA.Molecular mechanisms of glucocorticoid action and resistance [J].J Streoid Biochem Mol Biol,2003,83(1-5):37-48.
[13]Buttgereit F, Wehling M, Burmester GR.A new hypothesis of modular glucocorticoid actions:steroid treatment of rhenmatic disease revisited [J]. Arthritis Rheum,1998,41(5):761-767.
[14]Bray PJ, Cotton RG. Variations of the human glucocorticoid receptor geng (NR3C1):pathological and in vitro mutations and olymorphisms [J]. Hum Mutat,2003,21 (6):557-568.
[15]叶建伟,丁洁,黄建萍等.糖皮质激素受体基因多态性与肾病综合征患儿激素耐药相关性探讨[J].中华儿科杂志,2003,41(9)：661-665.
[16]Koper JW,Stolk RP,de Lange P,et al.Lack of association between five polymorphisms in the human glucocorticoid receptor gene and lucocorticoid resistance[J].Hum Genet,1997,99(5):663-668.
[17]Antonini SR, Latronico AC,Elias LL,et al. Glucocorticoid receptor gene polymorphisms in ACTH-secreting pituitary tumours[J]. Clin Endorcrinol (Oxf). 2002,57(5):657-662.
[18]de Lange P, Koper JW,Huizenga NA,et al. Differential hormone-dependent transcriptional actibation and-repression by naaturally occurring hunman glucocorticoid receptor variants[J].Mol Endocrinol,1997,11(8):1156-1164.
[19]Hillmann AG, Ramdas J,Multanen K,et al.Glucocorticoid receptor gene mutations in leukemic cells acquired in vitro and in vivo[J]. Cancer Res,2000, 60(7):2056-2062.
[20]Parks LL, Tumey MK, Detera-Wadleigh S,et al. An ACTH-producing small cell lung cancer expresses aberrant glucocorticoid receptor transcripts from anormal gene [J], Mol Cell Endocrino,1998,142(1-2):175-181.
[21]Longui CA,Vottero A,Adamsom PC,et al.Low glucocorticoid receptor alpha/beta ratio in T-cell lutmphoblastic leckemia[J].Horm Metab Res,2000, 32(10):401-406.
[22]Yudt MR, Jewell CM, Bienstock RJ, et al. Molcular origins for the dominant negative function of human glucocorticoid receptor beta[J].Mol Cell Boil 23(12):4319-4330.
[23]Pujols L, Mull J, Roca-Ferer J, et al. Expression of the human glucocorticoid receptor alpha and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone[J].Am Jrespir Cell MolBiol,2001,24(1):49-57.
[24]Lewis-Tuffin LJ, Cidlowski JA.The Physiology of human glucocorticoid receptorβ(hGRβ) and glucocorticoid resistance[J].Ann N Y Aead Sci,2006, 1069:1-9.
[25]Hamilos DL, Leung DY, Muro S, et al.Grbeta expression in nasal polyp inflammatory cells and its relaationship to the anti-inflammatory effects of intranasal fluticasone[J].J Allergy Clin Immunol,2001,108(1):59-68.
[26]Leung DY, Hamid Q, Vottero A, et al. Association of glucocorticoid in sensitivity with increased expression of glucocorticoid receptor beta[J].J The Journal of Experimental Medical,1997,186(3):1567-1574.
[27]Koga Y, Matsuzaki A, Suminoe A, et al.Differential mRNA expression of glucocortcoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphobastic leukemia in children[J].Pediatr Blood Cancer,2005,45(2):121-127.
[28]Lane SJ, Lee TH.Mechanisms of corticosteroid resistance in asthmastic patients [J].Int Arch Allergy Immunol,1997,113(1-3):193-195.
[29]Bailey S, Hall AG, Pearson AD, et al.Glucocorticoid resistance and the AP-1 transcription factor in leukaemia [J].Adv Exp Med Biol,1999,457:615-627.
[30]Liu DH,Su YP,Zhang W,et al.Changes in glucocorticoid and mineralocorticoid receptors of liver and Kinney cytosols after pathologic stress and its regulation in rats[J],Crit Care Med,2002,30(3):623-627.
[31]Miller AH, Pariante CM, Pearce BD.Effects of cytokines on glucocorticoid receptor expression and fuction. Glucocorticoid resistance and relevance to depression [J].Adv Exp Med Biol,1999,461:107-116.
[32]Biola A, Lefebvre P, P errin-Wolff M, et al. Interleukin-2 inhibits glucocorticoid receptor transcriptional activity through a mechanism involving STATS (signal transducer and activator of transcription 5) but not Ap-1[J]. Mol Endocrinol, 2001,15(7):1062-1076.
[33]周太光,王铮,夏彦等.雷公藤多甙对肾病综合征患儿糖皮质激素受体的影响及其临床意义[J].临床儿科杂志,2003,21(10)：612-614.
[34]杜娟,凌昌全,陈永安等.淫羊藿和熟地煎剂对糖皮质激素受体下调模型大鼠糖皮质激素受体的影响[J].中国中西医结合杂志,2003,28(1)：64-67.
[35]翁端怡,曾章超,郑健.肾康灵冲剂治疗小儿肾炎性肾病综合征临床探析[J].中国中西医结合肾病杂志.2005,6(9)：543-545.