成纤维细胞生长因子-2在肾脏疾病中的作用

成纤维细胞生长因子 2 (fibroblastgrowthfactor 2 ,FGF 2 )参与多种脏器的胚胎发育 ,具有致有丝分裂作用、促增殖和分化作用。近年来 ,关于FGF 2在各种肾脏疾病发病机制方面的研究逐步深入与明了。研究证明 ,FGF 2参与足细胞损伤、启动球囊黏连、导致肾小球硬化 ;参与肾小管上皮细胞损伤 ,介导肾小管上皮间质转分化 ,加速肾间质纤维化     

成纤维细胞生长因子-2在肾脏疾病中的作用

成纤维细胞生长因子-2(fibroblast growth factor-2，FGF-2)参与多种脏器的胚胎发育，具有致有丝分裂作用、促增殖和分化作用。近年来，关于FGF-2在各种肾脏疾病发病机制方面的研究逐步深入与明了。研究证明，FGF-2参与足细胞损伤、启动球囊黏连、导致肾小球硬化；参与肾小管上皮细胞损伤，介导肾小管上皮间质转分化，加速肾间质纤维化。     

肾小球系膜区微量IgM沉积在儿童微小病变型肾病综合征中的意义

目的 探讨肾小球系膜区微量IgM 沉积在儿童微小病变型原发性肾病综合征(PNS)中的意义。方法 以临床诊断为PNS、病理诊断为微小病变(MCD)及肾组织微量IgM 沉积的106 例患儿为研究组,无免疫复合物沉积的MCD 型PNS 患儿81 例为对照组,回顾性分析两组患儿的临床特点、微量IgM 沉积对糖皮质激素及免疫抑制剂疗效的影响。患儿均口服足量泼尼松治疗,对糖皮质激素耐药者或频复发者联用免疫抑制剂治疗。结果 研究组糖皮质激素耐药率高于对照组(27.2% vs 12.3%,PPP>0.05)。研究组和对照组频复发病例联用MMF 治疗后复发频率均显著减少(P结论 MCD 型PNS 患儿肾脏的微量IgM 沉积可能是糖皮质激素耐药及频复发的重要因素;糖皮质激素耐药及频复发患儿联用MMF 治疗可能是较好的治疗方案。     

碱性成纤维细胞生长因子对癫(癎)持续状态大鼠海马谷氨酸和γ-氨基丁酸的影响

目的 通过戊四氮癫(癎)持续状态大鼠模型,观察碱性成纤维细胞生长因子(bFGF)对海马组织内主要的兴奋性氨基酸与抑制性氨基酸--谷氨酸和γ-氨基丁酸动态变化的影响.方法 建立60 d大鼠戊四氮(PTZ)诱导癫(癎)持续状态模型,生理盐水(NS)注射作为对照,皮下注射bFGF进行干预,分4组:即NS组、NS+bFGF组、PTZ组、PTZ+bFGF组.选择处理后第3、7、14天三个时间点进行观察,采用高效液相法检测海马组织谷氨酸和γ-氨基丁酸含量.结果 发作后3、7、14 d PTZ组海马组织谷氨酸较NS组有显著升高(P<0.01),以发作后14 d升高更为明显,PTZ+bFGF组各时间点谷氨酸较PTZ组下降(P<0.05);γ-氨基丁酸含量在PTZ组各时间点亦大于NS组(P<0.05),以发作后14 d升高较为显著;PTZ+bFGF组发作后各时间点γ-氨基丁酸较PTZ组差异无统计学意义(P>0.05).结论 大鼠癫(癎)持续状态后一定时间内海马谷氨酸和γ-氨基丁酸增加,bFGF能够降低大鼠癫(癎)发作后异常增加的谷氨酸含量.     

微小残留病变检测在儿童急性白血病中的应用

近年来,儿童急性白血病（AL）治疗效果随化疗方案的改进和危险分层治疗的引入取得很大进展。但微小残留病变（MRD）仍然是影响AL预后的一大难题。MRD水平影响化疗方案的选择、复发风险的分级,同时还可用于判断预后。目前检测MRD的方法主要有流式细胞术（FCM）和PCR。随着二代测序技术（NGS）的不断成熟与发展,其在MRD检测尤其在干细胞移植（SCT）后MRD检测方面扮演着重要角色。本文对微小残留病变检测在儿童急性白血病中的应用进行综述。     

儿童微小病变型肾病综合征的诊断和治疗

微小病变型肾病综合征（MCNS）对糖皮质激素敏感,但极易复发,可转变为对激素依赖或激素耐药,治疗非常棘手。该病诊断标准国内外基本一致,但均无最优治疗方案。本文介绍国内外诊断标准,并重点比较治疗方案。国外所选药物与国内基本一致,但剂量和疗程差异较大。建议个体化及综合治疗,根据不同个体或同一个体不同病程、病理类型改变、药物反应、药物不良反应来不断调整用药,特别要强调坚持治疗和随访的重要性。     

碱性成纤维细胞生长因子在多柔比星肾病大鼠模型中的表达 鼠

目的观察碱性成纤维细胞生长因子（bFGF）在多柔比星诱导肾病大鼠肾 组织中的表达和分布,探讨bFGF在微小病变型肾病综合征（MCNS）中的作用。方法 雄性Wistar大鼠50只随机分为正常组（10只）、肾病组（40只）。肾病组一次性尾静 脉注射多柔比星5mg/kg,建立多柔比星肾病模型,于注射多柔比星后第3、7、14、 28天检测各组大鼠24h尿蛋白定量,并分批处死肾病组大鼠,于第28天处死正常组 大鼠,采用免疫组织化学法检测各组大鼠肾脏组织bFGF的表达,采用彩色图像分析 系统对bFGF的表达进行定量分析。采用SPSS 10.0软件对各组间差异进行t检验和 两变量间相关分析。结果1.肾病组大鼠尿蛋白排泄量逐渐增加,第7、14、28天与 正常组比较,均有显著性差异（Pa〈0.01）;2.在肾病组大鼠肾组织中,bFGF阳性反 应颗粒呈棕黄色染色,主要分布于肾小球足细胞和肾小管上皮细胞的胞质中,并沿 毛细血管襻分布;3.不同时期肾病组bFGF免疫组织化学阳性指数（PI）明显高于同 期正常组的bFGFPI,有显著性差异（Pa〈0.01）,且不同时期bFGF呈现不同程度的表 达;4.肾病组在不同时期bFGFPI的变化与24h尿蛋白的排泄量呈正相关 （r=0.720P〈0.01）。结论1.bFGF在MCNS肾脏组织中存在异常表达和分布。2.MCNS 中bFGF的表达和分布与蛋白尿的进展密切相关,bFGF可能是蛋白尿发生的原因之 一。3.bFGF可能在足细胞损伤发生中起重要作用,可作为判断肾小球足细胞损伤 的重要指标之一。     

病毒基因反式激活在微小病变型肾病发病中的作用

病毒基因反式激活是病毒影响细胞基因表达、诱发疾病发生的形式之一。微小病变型肾病综合征是小儿常见疾病,其病因和发病机制目前尚未完全阐明,而呼吸道病毒感染与本病的触发密切相关。本文就呼吸道病毒基因反式激活在该病触发中的作用作一综述。     

Recent advances in minimal change nephrotic syndrome

The etiology of MCNS remains an enigma. Increase in the permeability of the glomerular capillary filter to plasma proteins results in massive proteinuria and hypoalbuminemia which are the hallmarks of this disease. The cause of this increased permeability remains to be ascertained. Research in pursuit of this goal has led to the accumulation of fragmentary data on the morphological abnormalities, immunological dysfunction and metabolic changes that accompany this disease. In our experience, immunology dysfunctions, abnormalities of lipid profile and the deposition of IgM in the mesangium as detected by immunofluorescent microscopy are some of the unusual features of MCNS. The therapeutic implications of these findings and some of the other recent advances are discussed in this article.     

Nitric oxide synthase gene polymorphisms in children with minimal change nephrotic syndrome

Aims:  Nitric oxide (NO) attenuates many functions within the kidney, and all NO synthase (NOS) isoforms are constitutively expressed in the kidney. But the exact role of NO in renal diseases is still debatable. The aim of the present study was to investigate endothelial ( eNOS ), and neuronal ( nNOS ) NOS gene polymorphisms in children with minimal change nephrotic syndrome (MCNS).
Materials and methods:  Eighty-six Turkish children with clinical MCNS, ranging in age from 2 to 10 years, were compared with 114 healthy age- and sex-matched controls. The glu 298 Asp (G/T) polymorphism of the eNOS, and C276T (C/T) polymorphism of nNOS genes were genotyped using polymerase chain reaction.
Results:  The distribution of GG, TG, and TT genotypes for eNOS was 52%, 33% and 15% in MCNS compared with 61%, 26% and 13% in the controls ( P  > 0.05). The distribution of CC, TC, and TT genotypes for nNOS was 16%, 66% and 18% in MCNS compared with 10%, 43% and 47% in the controls. TT genotype distribution of nNOS was found to be lower in patients ( P  = 0.003). The eNOS and nNOS gene polymorphisms were not associated with gender, positive family history, frequency of relapses, or response to steroid.
Conclusions:  The present study is the first to investigate eNOS and nNOS gene polymorphisms in children with MCNS. The nNOS gene polymorphism may be associated with MCNS in children, but further studies in a larger population with different glomerular diseases are needed to confirm the results.     

糖皮质激素的基础及其在儿童肾病综合征中的临床应用

糖皮质激素是临床应用最广泛的药物之一,其在肾病综合征中更是得到了广泛应用.该文重点从糖皮质激素的基础如分类、临床剂量区分、作用机制、应用的基本原则、肾上腺轴被抑制与否的判断、注意事项及在肾病综合征中的临床应用等方面进行概述.     

Immunological profile in children with minimal change nephrotic syndrome

Peripheral blood from patients with active stage of minimal change nephrotic syndrome (MCNS) was examined for concanavalin A (ConA)-inducible suppressor T cell activity, proliferative response to phytohemagglutinin (PHA) and in the autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction, proportions of T cells with receptors for IgM (Tu) or IgG (T gamma) and the levels of serum immunoglobulin M, G and A. Six of 9 patients with MCNS studies showed deficiency of ConA-induced suppressor cell activity. In the AMLR, only one of 9 patients with MCNS demonstrated depressed proliferative response (p less than 0.05). In the allogeneic MLR, T cells from 5 of 9 patients with MCNS demonstrated poor proliferative response when stimulated with normal control non-T cells. Five of 9 patients with MCNS had depressed proliferative response to PHA. The proportion of total T cells, Tu cells and T gamma cells in the patient group were comparable to healthy control group. Serum IgG was significantly decreased in 7 of 11 patients. This study demonstrates multiple immunological abnormalities in patients with MCNS that might play a role in its pathogenesis.     

Cyclophosphamide in treatment of minimal change nephrotic syndrome

Nineteen children with the minimal change form of nephrotic syndrome were divided according to their pattern of response to prednisone: steroid-dependent and frequent relapsers. All patients received cyclophosphamide for 56 days in a single daily dose of 2.5 mg/kg (total 140 mg/kg), in order to prolong the length of remission. The percentage of patients who continued in remission at the end of the 1st, 2nd and 5th years was greater in the frequent-relapser group. This retrospective analysis confirms that the pattern of response to prednisone may be an important criterion for the selection of patients who will benefit from cyclophosphamide therapy.     

Steroid response pattern in Indian children with nephrotic syndrome

Gulati S, Kher V, Sharma RK, Gupta A. Steroid response pattern in Indian children with nephrotic syndrome. Acta Pædiatr 1994;83:530–3. Stockholm. ISSN 08033–5253
The steroid response pattern to standard prednisolone therapy is of immense diagnostic, therapeutic and prognostic value for the treating physician in managing children with nephrotic syndrome. None of the studies from our country has analysed the clinical, biochemical and histopathological profile in different steroid response categories. To address this problem we conducted a study comprising 127 children with nephrotic syndrome referred to our Institute. They were treated with oral prednisolone according to the APN protocol. Based on the subsequent response these children were classified into different steroid response categories on follow-up. Of the 116 children with follow-up of more than six months, infrequent relapsers constituted the majority (37.9%). The frequency of other steroid response categories was as follows: frequent relapsers (21.6%), steroid-dependent (18.1%), initial non-responders (17.3%) and subsequent non-responders (5.1%). The factors predicting a poor response to standard prednisolone therapy in our study were age of onset more than eight years, male sex, hypertension, microscopic haematuria and presence of non-minimal change nephrotic syndrome lesions on histopathology     

以肾病综合征为临床表现的儿童IgM肾病临床特征

目的 探讨以肾病综合征为临床表现的IgM肾病患儿的临床特征.方法 以2005年6月至2012年6月在湖南省儿童医院肾内科住院,临床诊断为肾病综合征、病理诊断为IgM肾病的36例患儿为研究对象(A组),以同期住院,病理诊断为微小病变的肾病综合征106例患儿为对照组(B组).随访1～8年,分析其临床特征.结果 (1)对照组、研究组患儿伴有血尿者分别为3.8％及30.6％(x2=20.403,P＜0.05).(2)研究组患儿肾脏病理构成:轻度系膜增生性病变26例(72.2％),中度系膜增生性病变9例(25％),1例为局灶节段性肾小球硬化.(3)将研究组按肾脏病理分成轻度病变组及中重度病变组,对照组、轻度病变组、中重度病变组患儿激素耐药率分别为12.3％、19.2％、77.8％(x2 =24.369,P＜0.05),对照组与轻度病变组之间差异无统计学意义(P＞0.05).(4)激素耐药者联用吗替麦考酚酯治疗,对照组、研究组激素耐药患儿的缓解率分别为50％及85.7％(x2=3.60,P＞0.05).结论 以肾病综合征为临床表现的IgM肾病患儿血尿的发生率较高,肾脏病理为中度病变以上者激素耐药发生率较高,需早期联合应用免疫抑制剂治疗,吗替麦考酚酯可能成为较好的免疫抑制剂选择方案.     

肾病综合征患儿肾组织P-糖蛋白170表达的研究

目的检测P-糖蛋白170(P-gp170)mRNA及蛋白在糖皮质激素(GC)敏感和耐药型肾病综合征(NS)患儿肾组织中的分布、表达变化,初探NS患儿肾组织P-gp170表达在GC耐药中的作用。方法2005-09—2006-04在中南大学湘雅二医院住院的初发特发性肾病(INS)患儿34例,按照GC对患儿的疗效分为GC敏感组(SSNS)和GC耐药组(SRNS),分别以免疫组织化学和原位杂交方法检测患儿肾组织P-gp170蛋白及mRNA的表达,6例正常肾组织为对照。结果正常对照组肾组织及NS患儿肾组织中均有P-gp170蛋白及mRNA的表达;正常对照组及NS患儿肾小球均无P-gp170蛋白及mRNA的表达,其蛋白及mRNA均主要表达于肾小管及肾间质,肾小管近端表达多于远端(P<0.01);免疫组化和原位杂交结果均显示SSNS阳性信号表达多于对照组,而SRNS又高于SSNS(P均<0.01);P-gp170蛋白与mRNA的表达成显著正相关(r=0.87,P<0.05)。结论肾脏本身即可合成、分泌P-gp170;P-gp170在正常肾小管的表达可能与某些代谢物质的转运有关;NS患儿肾小管P-gp170表达增高可能与NS本身的状态有关,或者是GC通过诱导P-gp170的表达增高而导致GC耐药;P-gp170表达上调可能为GC耐药的机制之一;检测肾组织P-gp170的表达水平有助于预测NS患儿GC反应差异性。     

利妥昔单抗对儿童难治性肾病综合征的治疗进展

难治性肾病综合征是导致儿童终末期肾脏病的主要原因之一,也是临床治疗的棘手问题.虽然包括免疫抑制剂在内的多种治疗方法已经对儿童难治性肾病综合征表现出了良好的治疗效果以及安全性,但是仍有很多患儿不能获得缓解.近年来,新型免疫抑制剂利妥昔单抗用于治疗难治性肾病综合征取得了较好效果,很多病例分析以及临床试验对利妥昔单抗治疗儿童难治性肾病综合征的有效性进行了报道.该文就该药治疗儿童难治性肾病的疗效和安全性等作一综述.