肾小管肝型脂肪酸结合蛋白对小鼠IgA肾病的肾脏保护作用

Objective To investigate the renoprotection of tubular L-FABP in murine IgA nephropathy (IgAN） induced by bone marrow transplantation(BMT). Methods IgAN models were reconstituted by BMT from IgAN-prone mice into mice (Tg) transgenically tubular overexpressing human L-FABP (hL-FABP) and wild type (WT) mice. These recipients were sacrificed at 6 and 12 weeks after BMT and their kidneys were collected. The expressions of hL-FABP, fibronectin (FN) and monocyte chemoattractant protein-1(MCP-1) mRNA were detected by real-time PCR. hL-FABP, FN, type Ⅳ collagen (Col Ⅳ), hemeoxygenase-1(HO-1) and 4-hydroxy-2-nonenal (4-HNE) modified proteins were detected by Western blotting. The distribution of hL-FABP and FN protein in kidney was detected by immunohistochemistry. The level of serum IgA, urinary albumin and urinary hL-FABP was detected by ELISA. Results (1) IgAN was reconstituted in both Tg and WT mice by BMT: mesangial IgA deposition and up-regulation of serum IgA. The levels were not significantly different between two groups (Tg-ddY and WT-ddY). (2) hL-FABP was expressed in proximal tubular cells of normal Tg mice. The mRNA (1.62±0.32 vs 0.46±0.09, P<0.01) and protein expression (1.74±0.76 vs 1.14±0.31, P<0.01) of hL-FABP was up-regulated in Tg-ddY kidney and urinary hL-FABP level (?滋g/g creatinine) was significantly increased (59.87±26.75 vs 31.01±14.86, P<0.05) at the 6th week after BMT. (3) WT-ddY mice showed a significantly higher urinary albumin level (mg/L) (828±656 vs 82±22, P<0.01), severer mesangial matrix expansion (P<0.01),more glomerular FN and Col Ⅳ deposition at the 12th week. (4) Up-regulation of renal hL-FABP was associated with significant suppression of renal HO-1 expression (P<0.05), accumulation of 4-HNE modified proteins (P<0.05) and MCP-1 mRNA expression (P<0.01) in Tg-ddY mice. Conclusion Tubular L-FABP may lessen the progression of glomerular damage at early stages of IgAN by reducing oxidative stress and inflammatory mediators.     

尿肝型脂肪酸结合蛋白预测慢性肾小球肾炎进展的价值

目的 评估尿肝型脂肪酸结合蛋白(L-FABP)预测慢性肾小球肾炎(CGN)病情进展的临床价值.方法 前瞻性入选2004年1月至2005年12月期间在我院行肾穿刺活检明确病理诊断的原发性CGN患者123例为对象,另选28例年龄、性别匹配的健康志愿者为对照.用酶联免疫吸附法检测肾穿刺前新鲜尿液L-FABP含量,同时常规检测各项血液及尿液指标.对所有患者进行5年随访,每3个月随访1次,在随访结束时分为疾病进展组和非进展组,评估影响CGN进展的危险因素.结果 与对照组相比,CGN患者尿L-FABP均值明显升高(P＜0.01).尿L-FABP与估计肾小球滤过率(eGFR)呈负相关(r=-0.565,P＜0.01);与尿蛋白量(r=0.501,P＜0.01)和Scr(r=0.601,P＜0.01)呈正相关.Kaplan-Meier分析显示,尿L-FABP＞76.58 μg/g·cr的CGN患者的预后显著变差.尿L-FABP预测CGN进展的ROC曲线下面积(AUC)为0.95.尿L-FABP为119.8 μg/g·cr时,其敏感性为87.5％,特异性为90.5％.结论 尿L-FABP可作为监测慢性肾小球肾炎疾病进展的新生物学标记物.     

尿肝型脂肪酸结合蛋白及其与尿中性粒细胞明胶酶相关脂质运载蛋白联合应用在成人心脏手术后急性肾损伤诊断中的作用

目的 探讨尿肝型脂肪酸结合蛋白( L-FABP)及其与尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)联合应用在预测成人心脏手术后急性肾损伤(AKI)的发生及严重程度中的价值,以期能为临床AKI的早期诊断提供方便可靠的方法.方法 前瞻性收集心脏手术患者术前、术后即刻及术后2h的血和尿标本,分别检测Scr、尿L-FABP和NGAL水平,比较AKI和非AKI患者术后各标志物的动态变化情况.运用受试者工作特征(ROC)曲线及曲线下面积(AUC)评估标志物单独及联合应用时诊断AKI的准确性.结果 总共109例患者中26例(23.9％)发生了AKI,其中AKIN Ⅰ、Ⅱ和Ⅲ期分别占46.2％ 、34.6％和19.2％.尿L-FABP 和NGAL水平在AKI组术后即刻及术后2h均显著高于非AKI组,其浓度变化明显早于Scr.两时间点各标志物单独预测AKI的发生及Ⅱ和Ⅲ期AKI的AUC均在0.81～0.87.用Logistic 回归方程联合术后同一时间点的尿NGAL和尿L-FABP,则术后即刻和术后2h预测术后AKI 及严重程度的精确性进一步提高( AUC=0.911～0.927).结论 尿L-FABP和尿NGAL在心脏术后AKI早期即显著升高,比Scr能更早地预测AKI的发生和严重程度,两者联合应用则可使诊断的精确性进一步提高.     

尿视黄醇结合蛋白、尿肝型脂肪酸结合蛋白、血成纤维细胞生长因子-21、血转化生长因子-β联合诊断早期糖尿病肾病的价值

目的 分析尿视黄醇结合蛋白(retinol binding protein,RBP)、尿肝型脂肪酸结合蛋白(liver type fatty acid binding protein,L-FABP)、血成纤维细胞生长因子-21(fibroblast growth factor-21,FGF-21)、转化生长因子-β(t...     

色素上皮衍生因子对高糖诱导人肾小球系膜细胞p38丝裂原活化蛋白激酶-cAMP反应元件结合蛋白通路及纤连蛋白的影响

目的 探讨色素上皮衍生因子(PEDF)对高糖条件下人肾小球系膜细胞( HMC )p38丝裂原活化蛋白激酶(p38MAPK)、cAMP反应元件结合蛋白(CREB)及细胞外基质成分纤连蛋白(FN)的影响.方法 体外予正常糖(5.6 mmol/L)、甘露醇(24.4 mmol/L)、高糖(30 mmol/L)、高糖+PEDF(30 mmol/L葡萄糖+10 nmol/L、40 nmol/L、100 nmol/L PEDF)培养基培养HMC 24 h,观察p38MAPK、CREB活性(Western印迹)及FN mRNA( RT-PCR)和蛋白( ELISA)的变化.结果 与正常糖及甘露醇组相比,高糖组p-p38MAPK、p-CREB、FN的表达均显著升高(均P＜ 0.01);与高糖组相比,PEDF干预组上述指标的表达均显著下降(均P＜0.05).结论 PEDF可能通过p38MAPK-CREB通路抑制糖尿病肾病的纤维化.