肾脏的发育及疾病的功能基因组学研究

近五十年来,发育生物学家已经研究了肾脏发育的有关形态发生的过程.然而,随着转基因小鼠的出现,基因组测序和功能基因组的出现,关于肾脏发育的基因组学方面的理解也越来越值得关注.而且许多疾病都是由肾脏发育缺陷造成的,比如肾炎综合症、肾脏发育异常、新生儿肾脏肿瘤.本文将讨论新的基因组方法 的出现是怎样促进对肾脏发育和肾脏疾病的...     

肾病综合征患者血清肽谱的差异性研究

目的比较肾病综合征患者与正常人的血清肽谱，寻找差异表达的血清肽谱。方法将研究对象分成试验组和对照组。试验组为49例肾病综合征患者，包括17例系膜增生患者、12例微小病变患者、10例膜性肾病患者和10例局灶硬化患者；对照组为10例健康志愿者。采用ClinProt磁珠浓缩和基质辅助激光解吸电离法分析两组研究对象血清肽谱的差异。结果系膜增生组VS对照组筛选出5个差异表达的多肽（15．28±7．61，P〈0．01）。微小病变组VS对照组筛选出7个差异表达的多肽（2．16±1．59，P〈0．01）。膜性肾病组vs对照组筛选出6个差异表达的多肽（35．48±13．71，P〈0．01）。局灶硬化组VS对照组筛选出5个差异表达的多肽（18．06±8．07，P〈0．05）。以P〈0．05为差异有统计学意义。采用遗传算法对样本进行分类并建立诊断预测模型，对区分系膜增生组、微小病变组、膜性肾病组、局灶硬化组与对照组的交叉验证能力分别为96．18％、100％、98．53％、94．12％，而识别率均为100％。结论应用蛋白质组学建立了肾病综合征患者的血清肽谱模型，为人们更好地了解肾病综合征的发病机制提供了新的思路。     

广西城市社区居民高尿酸血症流行病学调查及其与慢性肾脏病的关系

目的 通过社区人群筛查了解广西城市原住民中高尿酸血症(HUA)的患病率及其与慢性肾脏病(CKD)的关系,并探讨影响HUA肾损害的风险因素.方法 选择桂林市城区原住居民集中的象山社区,对18～75岁居民(n=6 273)采取横断面进行筛查.收集空腹血及晨尿进行血糖、肾功能、血脂、胰岛素和尿蛋白等检测,同时进行问卷调查和体格检查.结果 社区居民中HUA总患病率为23.5%,其中男性HUA患病率显著高于女性(28.4%对19.7%,P＜0.01).社区居民中CKD患病率为21.6%,其中男性居民CKD患病率较女性显著增高(24.9%对19.0%,P＜0.01).在HUA人群中CKD检出率显著高于尿酸正常人群(30.4%对18.9%,P＜0.01).男性HUA人群CKD检出率显著高于同性别正常血尿酸人群(34.3%对21.2%,P＜0.01),也显著高于女性HUA人群(25.9%,P＜0.01).Logistic回归分析发现,CKD仅与收缩压、低密度脂蛋白胆固醇和血糖水平独立相关(P＜0.01).结论 广西城市社区居民中HUA患病率显著增加,与CKD患病率增高有关,且血尿酸轻度增高即增加CKD患病率.

Abstract：

Objective To detect the prevalence of hyperuricemia and its relationship to chronic kidney disease(CKD) in the residents of Guangxi, and to discuss the risk factors for the hyperuricemia associated renal damage. Methods The residents aged 18-75 years old(n=6 273) in Xiangshan community,Guilin, were screened by means of cross-sectional study. Blood pressure was measured at 8:00-9:00.Fasting blood and urine samples were collected to determine blood glucose, lipid, insulin, creatinine, and urine albumin. Results The prevalence of hyperuricemia in the community residents was 23.5% in all cohort, being significantly higher in male residents than in female(28.4% vs 19.7%,P＜0.01). The prevalence of CKD was 21.6% in all cohort, and was 24.9% in males and 19.0% in females(P＜0.01). The prevalence of CKD was 30.4% and 18.9% respectively in residents with and without hyperuricemia(P＜0.01).The prevalence of CKD in males with hyperuricemia(34.3%) was significantly higher than in males without hyperuricemia(21.2%) and females with hyperuricemia(25.9%, all P＜0.01). CKD was only positively related to low-density lipoprotein cholesterol, blood glucose, and systolic blood pressure shown by logistic regression analysis. Conclusions The prevalence of hyperuricemia markedly increases in the urban residents, which contribute to the raised prevalence of CKD. Slightly elevated blood uric acid level is associated with raised prevalence of CKD.     

不同剂量咪唑立宾在临床肾移植中的应用研究

目的 探讨不同剂量咪唑立宾(MZR)在临床肾移植中的应用效果及其安全性.方法 将206例首次接受肾移植的受者按手术时间排序,以奇偶数将受者列入吗替麦考酚酯(MMF)组,MZRⅠ组和MZRⅡ组.MMF组受者术后采用MMF+环孢素A(CsA)+泼尼松(Pred)的免疫抑制方案,MZRⅠ组和MZRⅡ组采用MZR+CsA+Pred的免疫抑制方案;MMF组MMF的用量为1.0g/d,MZRⅠ组和MZRⅡ组MZR的用量分别为100和200mg/d,3组间CsA和Pred的用法相同.排除失随访受者,MMF组、MZRⅠ组和MZRⅡ组分别有100、60和30例受者获得完整随访,研究终点为肾移植术后5年.比较各组受者人、肾存活率和排斥反应发生率,以及与药物相关不良反应的发生情况等.结果 MZR Ⅰ组、MZRⅡ组和MMF组受者术后总体存活率分别为88.3%(53/60)、90%(27/30)和88%(88/100),移植肾总体存活率分别为85%(51/60)、86.7%(26/30)和86%(86/100),急性排斥反应发生率分别为10%(6/60)、6.7%(2/30)和9%(9/100),3组间人、肾存活率以及急性排斥反应发生率的差异均无统计学意义(P>0.05);严重肺部感染发生率分别为3.3%(2/60)、10%(3/30)和15%(15/100),MZRⅠ组显著低于MMF组(P<0.05),而MZRⅡ组与其他两组的差异均无统计学意义(P>0.05).MZR Ⅰ组和MZRⅡ组发生严重感染者均经治疗后痊愈,而MMF组死亡11例,死亡率为73.3%(11/15).MZRⅠ组和MZRⅡ组腹泻发生率均显著低于MMF 组(P<0.05),而高尿酸血症发生率均显著高于MMF组(P<0.05).结论 咪唑立宾对预防肾移植后排斥反应是安全、有效的,受者耐受性好,对于免疫功能低下易发生感染的高危人群,以及使用MMF致顽同性腹泻者,可将含咪唑立宾的免疫抑制方案作为首选.

Abstract：

Objective To observe the efficacy and safety of different doses of mizoribine to prevent rejection after renal transplantation. Methods Sorted by time of operation and odevity, 206 primary kidney transplant recipients were divided into 3 groups, including MMF group, MZR Ⅰ group and MZR Ⅱ group. All recipients in 3 groups were administrated CsA and Pred, combined with mycophenolate mofitile (MMF) in MMF group and mizoribine (MMF) in MZR Ⅰ and Ⅱ groups.The dosage of MMF was 1. 0 g/day, while dosage of MZR in MZR Ⅰ and Ⅱ groups was 100 and 200 mg/day, respectively. There was no difference in usage of cyclosporine (CsA) and prednisone (Pred) among 3 groups. 100, 60 and 30 recipients were followed up in MMF, MZR Ⅰ and MZR Ⅱ groups respectively in 5 years. During the follow-up period of 5 years, the incidence of acute rejection, patient/graft survival and adverse effects associated with drugs in three groups were observed. Results The patient/graft survival was 88. 3 % (53/60), 85 % (51/60) in MZR Ⅰ group, 90 % (27/30),86.7 % (26/30) in MZR Ⅱ group, and 88% (88/100), 86% (86/100) in MMF group, respectively (P>0. 05). There was no significant difference in incidence of acute rejection among MZR Ⅰ (10 %, 6/60), MZR Ⅱ (6. 7 %, 2/30) and MMF groups (9 %, 9/100). The incidence of severe pulmonary infection in MZR Ⅰ group was 3. 3 % (2/60), and 10 % (3/30) in MZR Ⅱ , and the former was lower than MMF group (15 %, 15/100) significantly. There was significant difference in mortality of severe pulmonary infection between MZR Ⅰ group (0, 0/2) and MMT group (73. 3 %, 11/15). The rate of ACR in MZR Ⅱ group (10 %, 3/30) was lower significantly than MMF group (30 %, 30/100) and MZR Ⅰ group (31.7 %, 19/60). There was significant difference in the incidence of hyperuricacidemia between two MZR groups (30 %, 56. 7 %) and MMF group (10 %)(P<0. 05), while the incidence of diarrhea and myelosuppression was lower significantly in MZR Ⅰ group than in MMF group. Conclusion MZR can prevent acute rejection after kidney transplantation effectively and safely. Immunosuppressive therapy including mizoribine is the best choice especially for high risk group because of susceptibility to infection and those who suffer from tenacious diarrhea owing to the side effect.     

肾祖细胞及其分化

哺乳动物的后肾,是由输尿管芽和作为肾祖细胞库的生后肾原基间相互诱导形成的。而肾祖细胞分化机制的了解和开始被阐明的生后肾原基的诱导方法,使我们离对复杂的肾细胞体系进行增殖与操作更近一步了。     

急性排斥反应移植肾组织转录因子活性变化

目的筛选与肾移植急性排斥反应相关的转录因子。方法应用转录因子芯片技术,在功能水平分析3份肾移植急性排斥反应患者病理组织与3份正常组织中细胞核内转录因子活性的差异,并作电泳迁移率变动分析验证芯片检测结果。结果与正常组织相比,在急性排斥反应移植肾病理组织标本中,从345个候选的转录因子中筛选出99个有活性差异的转录因子,其中活性上调的转录因子有95个,活性下调的转录因子有4个。电泳迁移率变动分析显示AP-1、Pbx1和MEF-2活性上调,与芯片分析结果一致。结论转录因子活性异常与肾移植急性排斥反应有关,这些异常可能有助于揭示肾移植急性排斥反应的分子生物学机制和预测指标及干预治疗的靶点。     

尿毒症患者血清肽谱的差异性研究

目的 比较尿毒症患者与正常人的血清肽谱,寻找差异表达的血清肽谱.方法 将研究对象分成试验组和对照组.试验组为30例尿毒症患者,包括10例未透析患者、10例腹膜透析患者和10例血液透析患者;对照组为13例健康志愿者.采用ClinProt磁珠浓缩和基质辅助激光解吸电离法分析两组研究对象血清肽谱的差异.结果 与对照组相比,未透析组、腹膜透析组、血液透析组分别筛选出7个、7个、9个显著表达的差异性多肽;比较未透析组与腹膜透析组、未透析组与血液透析组、腹膜透析组与血液透析组,分别筛选出2个、5个、1个显著表达的差异性多肽.采用遗传算法对样本进行分类并建立诊断预测模型,对区分未透析组、腹膜透析组、血液透析组与对照组的交叉验证能力分别为 99.30%、95.12%和98.61%,而识别率均为100%;对区分未透析组与腹膜透析组、未透析组与血液透析组、腹膜透析组与血液透析组的交叉验证能力分别为95.00%、90.59%和79.72%,识别率分别为96.88%、100%和100%.结论 应用蛋白组学建立了尿毒症患者的血清肽谱模型,为人们更好地了解尿毒症的发病机制提供了新的思路.     

46,XX,t（7;15）（q11.2;q22）伴胚胎停止发育一例

病例：患者：女,30岁,已婚,表型正常,常规体检无明显异常,婚后胚胎停止发育3次,时间均发生在4-5个月内。患者为独生女,否认父母及其本人近亲结婚,否认家族遗传病史。G显带核型分析发现其核型为：46,XX,t（7;15）（q11.2;q22）。