尿视黄醇结合蛋白与转铁蛋白评价婴幼儿喘息性疾病肾损害

尿微量蛋白测定作为提示早期肾损伤的一项重要指标 ,近年来日益受到儿科重视。 1998年 1月～ 2 0 0 1年 1月 ,我科对收住的 6 1例婴幼儿喘息性疾病患儿尿视黄醇结合蛋白(Retinol- Binding- Protein,RBP)和尿转铁蛋白 (TransferrinTRF)水平进行测定 ,了解婴幼儿喘息性疾病时肾功     

窒息新生儿尿视黄醇结合蛋白水平的变化及意义

目的探讨尿视黄醇结合蛋白（RBP）的变化在新生儿窒息后肾小管损伤中的意义及不同窒息程度新生儿尿RBP值随日龄的动态变化特点。方法对132例足月窒息新生儿（轻度窒息67例，重度窒息65例）和48例足月正常新生儿（对照组）在生后1、3、7、10天用酶联免疫吸附法监测尿RBP。结果①生后d．与对照组相比，窒息组尿RBP值显著升高（P〈0．001）。②重复测量资料方差分析显示，不同组别之间存在差异（P〈0．01），进一步用SNK检验，得出两两间的差异均有意义（P〈0．05）。③不同日龄3组新生儿尿RBP值变化的趋势不同（P〈0．01）。④重度窒息组尿RBP，、RBP，。值与对照组和轻度窒息组均有差异（P〈0．05）。结论①生后7天内新生儿肾小管功能发育不完善。对窒息新生儿应监测肾功能，特别是重度窒息需7—10天以上的肾功能随访。     

视黄醇结合蛋白4和内脂素与非酒精性脂肪肝的相关性研究

目的 探讨视黄醇结合蛋白4（retinol - binding protein 4,RBP4）和内脂素与非酒精性脂肪肝（non - alcoholic fatty liver disease,NAFLD）的相关性。方法 采用2011年于某医院进行体格检查的955名年龄＞25岁成年人中身高等一般指标和谷氨酰基转移酶（γ - glutamyl transferase,GGT）等生化指标完整的780名作为研究对象。分析不同组RBP4和内脂素的血压、肝功能等指标趋势,并采用logistic回归模型分析不同RBP4和内脂素水平与NAFLD患病风险的相关性。结果 NAFLD组RBP4（t = 5.892,P＜0.001）、内脂素水平（t = 6.788,P＜0.001）均高于正常组,随着RBP4的增加,内脂素水平呈现上升趋势（P趋势＜0.001）,随着内脂素的增加,RBP4水平呈现上升趋势（P趋势＜0.001）,调整年龄、性别、体质指数（body mass index,BMI）、内脂素及肝功等各生化因素后,RBP4水平对NAFLD患病没有影响（OR = 1.518,95%CI:0.795～2.899）。调整年龄、性别、BMI、RBP4及肝功能等各生化因素后,内脂素仍是NAFLD的危险因子（OR = 2.268,95%CI:1.117～4.606）。结论 RBP4与NAFLD密切相关,但不是独立的危险因素。内脂素是NAFLD的独立影响因素。     

Increased mitochondrial function downstream from KDM5A histone demethylase rescues differentiation in pRB-deficient cells

The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cell cycle progression. Increasing evidence suggests that pRb also promotes differentiation, but the mechanisms are poorly understood, and the key question remains as to how differentiation in tumor cells can be enhanced in order to diminish their aggressive potential. Previously, we identified the histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein counteracting pRB''s role in promoting differentiation. Here we show that loss of Kdm5a restores differentiation through increasing mitochondrial respiration. This metabolic effect is both necessary and sufficient to induce the expression of a network of cell type-specific signaling and structural genes. Importantly, the regulatory functions of pRB in the cell cycle and differentiation are distinct because although restoring differentiation requires intact mitochondrial function, it does not necessitate cell cycle exit. Cells lacking Rb1 exhibit defective mitochondria and decreased oxygen consumption. Kdm5a is a direct repressor of metabolic regulatory genes, thus explaining the compensatory role of Kdm5a deletion in restoring mitochondrial function and differentiation. Significantly, activation of mitochondrial function by the mitochondrial biogenesis regulator Pgc-1α (peroxisome proliferator-activated receptor γ-coactivator 1α; also called PPARGC1A) a coactivator of the Kdm5a target genes, is sufficient to override the differentiation block. Overexpression of Pgc-1α, like KDM5A deletion, inhibits cell growth in RB-negative human cancer cell lines. The rescue of differentiation by loss of KDM5A or by activation of mitochondrial biogenesis reveals the switch to oxidative phosphorylation as an essential step in restoring differentiation and a less aggressive cancer phenotype.     

Plasma Retinoid Concentrations Are Altered in Pregnant Women

Vitamin A is vital to maternal–fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25–28 weeks gestation and 28–32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25–28 weeks gestation, plasma retinol (−27%), 4-oxo-13-cis-retinoic acid (−34%), and albumin (−22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28–32 weeks gestation, plasma retinol (−41%), retinol binding protein 4 (RBP4; −17%), transthyretin (TTR; −21%), albumin (−26%), 13-cis-retinoic acid (−23%) and 4-oxo-13-cis-retinoic acid (−48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum.     

2型糖尿病合并非酒精性脂肪性肝病患者血清视黄醇结合蛋白4水平变化及影响因素的研究

目的 研究T2DM合并非酒精性脂肪性肝病（NAFLD）患者血清视黄醇结合蛋白4（RBP4）水平变化.方法 选取单纯T2DM患者（T2DM） 32例,T2DM合并NAFLD者（T2DM＋NAFLD）31例及正常对照（NC）者34名,测定血清RBP4水平,并计算胰岛β细胞功能指数（HOMA-β）及葡萄糖处置指数（DI）.结果 与其他两组比较,T2DM＋ NAFLD组血清RBP4水平最高（P＜0.05或P＜0.01）,而DI最低（P均＜0.01）.且TG、WC、SBP、DI是RBP4的独立影响因素（P均＜0.05）.RBP4是T2DM合并NAFLD独立危险因素（OR=1.142,P=0.057）.结论 血清RBP4在T2DM＋NAFLD组最高,与胰岛β细胞功能密切相关.     

过氧化物酶体增殖物激活受体-γ激动剂对高脂喂养SD大鼠血清视黄醇结合蛋白4水平的影响

目的 观察高脂喂养及吡咯列酮干预对SD大鼠视黄醇结合蛋白4（RBP4）水平的影响.方法 雄性SD大鼠随机分为3组,分别给予普通饮食（NC组）、高脂（F组）及高脂吡咯列酮（F＋Pio组）干预,第8、12周时行OGTT及胰岛素释放试验（ITT）,评价胰岛功能.检测FPG、血脂、肝功能及血清RBP4水平,并对肝脏、附睾脂肪和肾周脂肪称重,计算肝脏质量/体质量及脂肪质量/体质量.结果 8周后,F组FPG、血脂、胰岛素及OGTT血糖曲线下面积（AUCOGTT）、AUCITT均高于NC组（P＜0.05或P＜0.01）,血清RBP4水平升高（P＜0.01）;12周后,与F组相比,F＋Pio组FPG、胰岛素、TG、TC、AUCOOGTT、AUCITT、肝脏质量/体质量及脂肪质量/体质量和血清RBP4水平降低（P＜0.05或P＜0.01）.结论 PPAR-γ激动剂吡咯列酮能减轻糖脂毒性、改善IR并降低体内RBP4水平.     

大鼠急性肺血栓栓塞后血中DBP、RBP和TTR表达降低

目的探讨急性肺血栓栓塞时维生素D结合蛋白(DBP)、维生素A结合蛋白(RBP)和甲状腺素转运蛋白(TTR)的表达变化及对代谢的影响。方法用颈静脉插管注入血栓的方法制备大鼠急性肺栓塞模型。用Western blot检测DBP、RBP和TTR蛋白水平,RT-PCR法检测肝组织中DBP、RBP和TTR的mRNA水平,放射免疫法测定FT4和25(OH)D3的血清浓度,微量荧光法测定维生素A的血清浓度。结果急性肺栓塞后血清中DBP、RBP和TTR的蛋白水平,肝组织中DBP、RBP和TTR的mRNA水平均逐渐降低;而血清中这3个结合蛋白的配体FT4、25(OH)D3和维生素A的水平明显升高。结论急性肺栓塞后血清中DBP、RBP和TTR的蛋白水平降低是由于肝细胞合成减少所致,从而释放出更多的配体。升高的25(OH)D3、维生素A和FT4分子在急性肺栓塞后的一系列病理生理变化中将发挥重要作用。     

妊娠期糖尿病孕妇血清视黄醇结合蛋白4水平变化及临床意义

目的了解妊娠期糖尿病（GDM）孕妇血清视黄醇结合蛋白4（RBP4）水平变化及临床意义。方法采用酶联免疫吸附试验（ELISA）测定50例孕晚期GDM孕妇及50例正常孕晚期孕妇血清RBP4水平,同时测定两组孕妇空腹血糖（FPG）、糖化血红蛋白（HbAlc）、空腹胰岛素（FINS）水平,计算稳态模型评估的胰岛素抵抗指数（HOMA-IR）及胰岛β细胞分泌功能指数（HOMA-β）。结果（1）GDM组孕妇血清RBP4水平为（18．48±4．60）ng/ml,明显高于正常孕妇血清RBP4水平（13．26±2．35）ng/ml（P〈0．01）。（2）GDM组孕妇FPG、HbAlc、FNS水平分别为（5．40±0．57）mmoL/L、（5．68±0．58）％、（9．32±1．30）mmoL/L,明显高于正常孕妇血清水平（4．99±0．27）mmoL/L、（4．75±0．51）％、（8．24±0．77）mmoL/L（P均〈0．01）。（3）GDM组孕妇HOMA—IR为（2．24±0．43）,明显高于正常孕妇（1．82±0．24）（P〈0．01）;GDM组孕妇HOMA-β为（107．29±35．54）,正常孕妇为（112．02±19．35）（P〉0．05）。（4）Pearson相关分析结果显示,两组孕妇血清RBP4水平分别与HbAlc、FINS呈显著正相关性（r=0．400,0．266,P〈0．05）;与HOMA-IR、HOMA-β无明显相关性（r=0．072,0．029,P〉0．05）。结论GDM孕妇血清RBP4水平明显升高,RBP4可能参与了GDM孕妇糖代谢紊乱,但是RBP4与GDM孕妇胰岛素抵抗无明显相关性;GDM孕妇尚不存在胰岛B细胞功能异常。