目的:探讨肾间质纤维化的机制及促红细胞生成素对肾衰竭的影响.方法:健康雄性清洁级Wistar大鼠40只,体重(200±20)g.随机分为4组:单侧输尿管结扎组(A组,7 d),单侧输尿管结扎组(B组,14 d),治疗组(C组,7 d),治疗组(D组,14 d),各组10只,术后C组、D组皮下注rh-EPO,从术后第3天起以rh-EPO2000IU/Kg皮下注射,1次/隔日.A组、C组分别于术后第7天放血处死,B组、D组分别于术后第14天放血处死,其后病理HE染色,Masson染色结果分析,TGF-β1免疫组化表达分析,免疫荧光检查reca-1.结果:实验组较对照组大体改变轻微;HE染色炎性细胞浸润减少,肾小管扩张程度减轻,Masson染色胶原减少,TGF-β1表达下降,免疫荧光红色增强.结论:促红细胞生成素可以促进肾脏血管新生的能力,减轻肾纤维化,进而起到对慢性肾功能损伤的修复作用.

目的 通过肾脏动脉夹闭的方法制成急性肾损伤模型,并通过相关指标的检测证实干细胞的保护作用及相关机制.方法 通过提取小鼠胫骨骨髓采取贴壁培养的方法体外培养扩增骨髓间充质干细胞,为了进一步在体内追踪干细胞,在将干细胞注入模型鼠体内之前,将干细胞用绿色荧光染料(CMFDA)染色,并通过尾静脉注射的方法注入到急性缺血再灌注小鼠模型鼠体内,在不同时间点通过检测肾脏功能及体质量,并通过肾脏病理HE染色及免疫荧光染色的方法观察增生细胞及管周毛细血管等指标比较骨髓间充质干细胞的肾脏保护作用.结果 经流式细胞仪检测、免疫荧光及光镜证实培养的细胞具有典型的干细胞形态及细胞表面分子标记物,注入小鼠体内的干细胞可以特异性被招募到受损肾脏,注入干细胞后明显促进急性缺血再灌注小鼠模型的肾脏功能、体质量及生存率,促进细胞再生并减少肾脏管周毛细血管的丢失,促进肾脏病理的改善.结论 骨髓间充质干细胞促进急性缺血再灌注肾脏损伤的修复.

1968年,Berger和Hinglais首次提出了IgA肾病( IgAN) [1] ,其诊断依赖于肾脏组织活检观察到以IgA为主的免疫球蛋白沉积于肾小球系膜区,常伴有补体C3沉积,偶有IgG和(或) IgM沉积. IgA肾病临床表现多样,反映了广泛的组织学变化,从光学显微镜下的近乎正常的外观到新月体的严重坏死病变[2] , IgA肾病的预后也不尽相同,但大多数病例都会有不同程度的肾功能损害,据相关研究报道,10年后大约有10％ ～60％的患者进展为终末期肾病,20年后该比例约为40％ [3].

肾脏意义的单克隆免疫球蛋白病(MGRS)是由国际肾脏病和单克隆免疫球蛋白病研究组于2012年首次提出的一种副蛋白血症肾损伤[1].近年来随着对肾脏疾病研究的深入,MGRS引起更多学者的关注.这类疾病的提出是为了区分良恶性血液疾病导致的单克隆免疫球蛋白病[1-2],MGRS的临床表现包括血尿、蛋白尿、肾功能异常,以及副蛋白血症引起的其他脏器损伤.针对单克隆免疫球蛋白病的靶向治疗,可以延缓患者的肾功能恶化,减少肾移植后的复发[3-4].我们对MGRS的分类、机制、诊断及治疗作一综述.

慢性肾脏疾病是严重威胁人类健康的常见疾病,2012年一项调查发现中国慢性肾病发病率达10.8%[1],成为继心脑血管病、肿瘤、糖尿病之后又一严重威胁人类健康的疾病,但目前还无有效治疗手段。肾纤维化是多种慢性肾脏疾病的主要病理改变,是终末期肾脏病的共同结局,其病理特点包括细胞外基质增多、肾小管扩张或萎缩、细胞凋亡等。因此,寻找肾纤维化新的治疗靶点,减缓和逆转慢性肾脏疾病进程,对于指导临床、改善肾病患者生活质量具有重要意义。

微核糖核酸( microRNA)是短的非编码的内源性RNA,结合到其靶mRNAs,并组装到相应的 RNA 诱导的沉默复合物( RISC)中。 miRNA的生物合成包括多个步骤。首先, miRNA在细胞核通过RNA聚合酶Ⅱ或RNA聚合酶Ⅲ转录为具有发夹径环结构的初级miRNA( PRI-MIR)。初级miRNA( PRI-MIR)被RNaseⅢ型核酸内切酶Drosha及其辅酶DGCR8剪切成双链短miRNA前体( Pre-miR)[1]。三磷酸鸟苷( GTP)和输出蛋白5能够将Pre-miR从细胞核转运到细胞质中[2]。细胞质中Pre-miR被另一种RNaseⅢ型核酸内切酶Dicer及其辅助因子剪切加工成为20~22个核苷酸左右的有活性的、成熟的miRNA[3]。并组装到RNA诱导的沉默复合体( RISC)上,并由RISC介导其与靶mRNAs结合,通过抑制靶mRNAs的翻译或降解靶mRNAs起作用。因此,miRNA能够通过mRNA的降解,翻译抑制或转录后抑制来调控基因的表达。

<正>脂蛋白(a)[lipoprotein(a),Lp(a)]是众多血浆脂蛋白中的一种,参与人体各系统的脂质代谢,除此之外还参与非脂质途径的多种代谢。慢性肾脏病(chronic kidney diseases,CKD)是一种代谢性疾病,Lp(a)对CKD的发生发展起着重要作用,本文就Lp(a)的作用及其导致肾损害机制的研究进展作一综述。

Objective To investigate the protective role of bone marrow-derived stem cells (BMDSCs) in progressive glomerulosclerosis rats,and to observe whether BMDSCs promote glomenlar repair and regeneration.Methods Progressive glomerulosclerosis was induced in enhanced green fluorescent protein (EGFP) bone marrow chimeric rats by injecting with anti-Thy1.1 antibody,followed by unilateral nephrectomy.Subsequently,these rats were treated with either BMDSCs infusion (treatment group,10 rats) or phosphate-buffered saline (untreated group,1O rats).Renal function and histological alterations were examined at week 12 after Thy1.1 antibody injection.Repair and regeneration of glomerular endothelial cells was detected by immunofluorescence.Results Only 3 rats survived in untreated group,other 7 rats died at week 2,7,9,11 after antibody injection.In treatment group,9 rats survived at week 12,only 1rat died at week 10.The BUN and Scr were significantly lower in treatment group as compared to untreated group [BUN(43.55±29.06) vs (76.58±66.19) mmol/L,Scr (138.79±75.14) vs (233.38±164.43) μmol/L].Proteinuria was not significantly different between two groups at day 3,7,14 and 28,while it was significantly decreased at day 42,56 and 84 in treatment group compared with untreated group.Light microscopy showed that there was severe diffuse mesangial cell proliferation,mesangial matrix expansion and glomerulosclerosis in untreated group,and such changes were ameliorated in treatment group.The mesangial expansion index and glomerular sclerosis index in untreated group was significantly higher than those in treatment group.More BMDCs were recruited into the glomeruli and differentiated into glomerular endothelial cells in treatment group as compared with untreated group.Double immunofluorescence stain also demonstrated that BMDSCs infusion promoted glomerular capillary repair and regeneration.Conclusion BMDSCs infusion can improve renal function and histological changes,and promote the repair and regeneration of glomerular capillary.

Objective To investigate the mechanism of antioxygen reaction of epigallocatechin-3-gallate (EGCG) in renal tubular epithelial cells of rats with oxidative stress induced by H2O2. Methods Cultured cells were divided into control group, H2O2 group and EGCG group. Cell survival was observed with MTT. The expressions of Nrf2 mRNA and -γ-GCS mRNA in cultured cells were examined by real time quantitative PCR. Immunohistochemistry and western blotting were used to detecte the expressions of Nrf2 and γ-GCS protein. Results The survival rate of tubular cells was 97. 61 ± 6.33 in control group. There was a significant decrease in H2 O2 group (56. 38 ± 5.57) (P < 0.01), while increased when the EGCG concentration were 5,10,20 mg/L(77.42 ±5.31,83.27 ±5.94,90.24 ±5.72) (P <0.05,P <0.01). EGCG up-regulated the expressions of Nrf2 and γ-GCS mRNA and protein in renal tubular epithelial cells with dose depen-dentment. Conclusion The expressions of Nrf2 and-γ-GCS increase in renal tubular epithelial cells with oxidative stress. Resulting from suppression of oxidative stress,EGCG exerts protective effect on NRK,and this antioxidative effect may be partly induced by activating the Nrf2 signal pathway.

[目的]探讨氧化应激对大鼠肾小管上皮细胞(NRK)生物学行为的影响及L -表没食子儿茶素没食子酸酯(L -EGCG)对NRK细胞氧化性损伤的保护作用.[方法]利用H2O2刺激离体培养的NRK细胞建立氧化损伤的模型,筛选H2O2对NRK细胞损伤研究的最适剂量与最佳时点.然后将培养细胞分EGCG正常对照组、H2O2组、不同浓度儿茶素组.MTT法检测细胞活力,流式细胞仪测定细胞凋亡,荧光探针JC-1测定线粒体膜电位.利用生物化学法检测各组NRK细胞培养上清中丙二醛(MDA)含量及乳酸脱氢酶(LDH)漏出量.[结果]①250 μmol/L H2O2作用6 h剂量组即可引起NRK细胞损伤;②L-EGCG能明显改善H2O2导致的细胞损伤,可使细胞存活率升高,LDH释放量降低,MDA生成减少,稳定了线粒体膜电位,减轻了细胞凋亡.[结论]氧化应激能导致大鼠肾小管上皮细胞活力下降,凋亡增加,L-EGCG可能是通过提高NRK细胞的抗氧化能力而提高其对H2O2损伤的保护及损伤修复能力.

<正>持续不卧床腹膜透析(CAPD)患者普遍存在营养不良状态,本研究探讨腹膜转运特性对CAPD患者营养状况的影响,并分析两者在透析充分性判定中的地位。