初发过敏性紫癜患儿肾脏受累危险因素分析

目的 对初发过敏性紫癜(HSP)患儿进行随访,探讨HSP患儿肾脏受累的危险因素.方法 前瞻性纳入2009年12月至2010年11月在南京医科大学附属南京儿童医院肾脏科住院的初发HSP患儿,随访6个月,根据肾脏受累定义,将HSP患儿分为肾脏受累组和无肾脏受累组.复习文献提取与肾脏受累可能相关的3项人口学特征、8项临床症状...     

NADPH oxidase-derived reactive oxygen species involved in angiotensin Ⅱ-induced monocyte chemoattractant protein-1 expression in mesangial cells

Objective To investigate the origin of oxidative stress induced by angiotensin H (Ang Ⅱ ) in human mesangial cells and the role of reactive oxygen species ( ROS) in Ang Ⅱ -induced monocyte chemoattractant protein-1 (MCP-1) expression.Methods MCP-1 expression was determined by real time RT-PCR.ROS production was measured by DCFDA fluorescence.Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was examined by lucigenin chemiluminescence.p47phox and p67phox translocation was assayed by Western blot.Twenty-four male mice were randomly divided into three groups; the control,the Ang Ⅱ infusion [ Ang Ⅱ 400 ng/(kg±min) ],and the apocynin treatment.Ang Ⅱ was infused by subcutaneously osmotic minipump for 14 days.Urinary albumin and 8-isoprostane excretion were measured by ELISA.Results In cultured human mesangial cells,Ang Ⅱ induced the MCP-1 expression in a dose-dependent manner with 3.56 fold increase as compared with the control.Ang Ⅱ increased intracellular ROS production as early as 3 min with the peak at 60 min and was in a time and dose-dependent.Incubation with different dosages of Ang Ⅱ ( 1μmol/L,10μmol/L,and 100μmol/L Ang Ⅱ ) for 60 min,ROS production increased at 1.82,2.92,and 4.08 folds respectively.Ang Ⅱ-induced ROS generation was sensitive to diphenyleneiodonium sulfate (DPI,10 μmol/L) and apocynin (500μmol/L) ,two structurally distinct NADPH oxidase inhibitors.In contrast,inhibitors of other oxidant- producing enzymes,including the mitochondrial complex I inhibitor rotenone,the xanthine oxidase inhibitor allopurinol,the cyclooxygenase inhibitor indomethacin,the lipoxygenase inhibitor nordihydroguiaretic acid,the cytochrome P450 oxygenase inhibitor ketoconazole and the nitric oxide synthase inhibitor G-nitro-L- arginine methyl ester were without an effect Ang Ⅱ -induced ROS generation was inhibited by the ATI antagonist losartan (10μmol/L) but not the AT2 antagonist PD123319 (10μmol/L).Ang Ⅱ treatment induced translocation of cytosolic of p47 and p67 to the membrane.The antioxidants almost abolished Ang Ⅱ -induced MCP-1 expression.Ang Ⅱ infusion increased urinary and p67 translocation by 2.69-,2.97-,and 2.67-fold,respectively.Conclusions NADPH oxidase-derived ROS is involved in Ang Ⅱ-induced MCP-1 expression.Inhibition of NADPH oxidase alleviates Ang Ⅱ -induced renal injury.     

儿童毛细血管内皮细胞增生性紫癜性肾炎的临床病理及预后分析

目的 探讨以弥漫性毛细血管内皮细胞增生为主要病理表现的紫癜性肾炎（DEP-HSPN）的临床、病理及预后。 方法 回顾性分析本院近10年来经肾活检确诊的8例DEP-HSPN患儿临床、病理和预后资料,并分别与同病理级别或具有同等蛋白尿水平（肾病水平蛋白尿）的非DEP-HSPN患儿进行比较。 结果 （1）DEP-HSPN起病急,临床表现重,8例患儿中,4例临床表现为肾炎性肾病,3例表现为肾病水平蛋白尿伴血尿,1例呈急性肾炎综合征,4例患儿合并有肉眼血尿。病理分级均为Ⅲ-b级,光镜主要表现为弥漫性毛细血管内皮细胞和系膜细胞增生,常合并毛细血管袢坏死及肾小球内炎性细胞浸润,4例患儿合并细胞性新月体。（2）与病理为Ⅲ-b级的非DEP-HSPN患儿比较,DEP-HSPN患儿病程较短,临床多见肉眼血尿,24 h尿蛋白量高,更多呈肾炎性肾病表现。病理上,DEP-HSPN肾小球毛细血管袢坏死更常见。与具有肾病水平蛋白尿的非DEP-HSPN患儿相比,DEP-HSPN合并新月体的比例较低。（3）8例患儿均采用口服泼尼松联合静脉滴注环磷酰胺（CTX）冲击,病程早期给予2个疗程甲泼尼龙冲击治疗方案。平均随防（7.00±2.20）月,1例临床痊愈,5例持续镜下血尿,2例微量蛋白尿及持续镜下血尿。两组患儿预后差异无统计学意义。 结论 DEP-HSPN起病较急,临床以大量蛋白尿或肾炎性肾病为主要表现,并且常合并肉眼血尿。病程早期给予积极的免疫抑制剂治疗常能取得较满意的近期疗效。     

微管解聚剂秋水仙碱抗肾间质纤维化的研究

肾间质纤维化是以肾间质纤维组织增生、炎症细胞浸润和肾小管萎缩、扩张为基础，是各种肾脏病慢性进展的最终结果。近来的研究表明微管解聚剂秋水仙碱对肝脏纤维化、肺纤维化、酒精性肝硬化等均显示出一定的预防和治疗效果犤１，２犦。为了明确秋水仙碱对肾间质纤维化是否同样具有防治作用以及其效果如何，本研究通过单侧输尿管结扎（UUO）肾间质纤维化动物模型进行了形态学的初步探讨。１材料和方法１．１实验动物分组及模型制备SD雄性大鼠２６只，随机分成３组：预防组（１０只），UUO基础上予秋水仙碱１００μg／kg·d－１腹腔注射每…     

NADPH oxidase-derived reactive oxygen species involved in angiotensin Ⅱ-induced monocyte chemoattractant protein-1 expression in mesangial cells

Objective To investigate the origin of oxidative stress induced by angiotensin H (Ang Ⅱ ) in human mesangial cells and the role of reactive oxygen species ( ROS) in Ang Ⅱ -induced monocyte chemoattractant protein-1 (MCP-1) expression.Methods MCP-1 expression was determined by real time RT-PCR.ROS production was measured by DCFDA fluorescence.Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was examined by lucigenin chemiluminescence.p47phox and p67phox translocation was assayed by Western blot.Twenty-four male mice were randomly divided into three groups; the control,the Ang Ⅱ infusion [ Ang Ⅱ 400 ng/(kg±min) ],and the apocynin treatment.Ang Ⅱ was infused by subcutaneously osmotic minipump for 14 days.Urinary albumin and 8-isoprostane excretion were measured by ELISA.Results In cultured human mesangial cells,Ang Ⅱ induced the MCP-1 expression in a dose-dependent manner with 3.56 fold increase as compared with the control.Ang Ⅱ increased intracellular ROS production as early as 3 min with the peak at 60 min and was in a time and dose-dependent.Incubation with different dosages of Ang Ⅱ ( 1μmol/L,10μmol/L,and 100μmol/L Ang Ⅱ ) for 60 min,ROS production increased at 1.82,2.92,and 4.08 folds respectively.Ang Ⅱ-induced ROS generation was sensitive to diphenyleneiodonium sulfate (DPI,10 μmol/L) and apocynin (500μmol/L) ,two structurally distinct NADPH oxidase inhibitors.In contrast,inhibitors of other oxidant- producing enzymes,including the mitochondrial complex I inhibitor rotenone,the xanthine oxidase inhibitor allopurinol,the cyclooxygenase inhibitor indomethacin,the lipoxygenase inhibitor nordihydroguiaretic acid,the cytochrome P450 oxygenase inhibitor ketoconazole and the nitric oxide synthase inhibitor G-nitro-L- arginine methyl ester were without an effect Ang Ⅱ -induced ROS generation was inhibited by the ATI antagonist losartan (10μmol/L) but not the AT2 antagonist PD123319 (10μmol/L).Ang Ⅱ treatment induced translocation of cytosolic of p47 and p67 to the membrane.The antioxidants almost abolished Ang Ⅱ -induced MCP-1 expression.Ang Ⅱ infusion increased urinary and p67 translocation by 2.69-,2.97-,and 2.67-fold,respectively.Conclusions NADPH oxidase-derived ROS is involved in Ang Ⅱ-induced MCP-1 expression.Inhibition of NADPH oxidase alleviates Ang Ⅱ -induced renal injury.     

姜黄素的研究进展

姜黄素是姜黄中提取的一种植物多酚 ,也是姜黄发挥药理作用最重要的活性成分。近年的研究不仅证明了姜黄的传统作用 ,而且还揭示出一些新的药理作用 ,如抗炎、抗氧化、清除氧自由基、抗人类免疫缺陷病毒、保护肝脏和肾脏、抗纤维化以及防癌抗癌等作用 ,可能与其抑制核因子 κB和激活蛋白 1等转录因子的激活及表达有关 ,而且无明显的毒副作用。本文就姜黄素的研究进展作一综述。     

儿童紫癜性肾炎的治疗进展

过敏性紫癜(HSP)是以全身性坏死性小血管炎为主要病理改变的疾病。临床以皮肤紫癜、关节炎、胃肠道病变以及肾脏损害为特点的综合征。紫癜性肾炎是指HSP引起的肾脏损害。临床上在HSP病程中(包括病程6个月以内)出现血尿和(或)蛋白尿即可诊断。HSP的病因不明,多认为与感染和变态反应有关。免疫功能紊乱是本病主要发病机制。本文就该病在激素、免疫抑制剂、抗血小板聚集剂、抗凝剂、血管扩张剂、抗氧化剂、中药、血浆置换和肾移植方面的治疗进展予以综述。     

CD4+T淋巴细胞表面CD40L的表达在小儿川崎病血管损伤中的作用机制

目的:通过检测川崎病患儿静脉输注丙球治疗前后外周血T细胞表面CD40L(CD154)表达,探讨川崎病冠状动脉损伤的发病机制。方法:采用流式细胞仪检测26例川崎病患儿静脉输注丙球治疗前后、16例其他发热性疾病患儿、15例正常儿童外周血T细胞表面的CD40L表达。采用酶联免疫吸附试验检测相应血清中可溶性CD40L。结果:川崎病患儿CD4 T细胞表面CD40L表达(66.26±6.71)%显著高于其他发热性疾病对照组(58.11±6.35)%及正常儿童对照组(46.96±4.27)%,川崎病患儿静脉输注丙球治疗后明显下降(58.86±7.49)%。川崎病患儿血清中可溶性CD40L(17.36±5.72)ng/ml亦显著高于其他发热性疾病对照组(12.17±4.28)ng/ml及正常儿童对照组(7.48±3.59)ng/ml,静脉输注丙球治疗后无明显下降(16.46±5.12)ng/ml。CD4 T细胞表面CD40L表达与川崎病冠状动脉损伤有关,而CD8 T细胞表面CD40L的表达及可溶性CD40L与冠状动脉损伤无关。川崎病患儿CD4 T细胞表面CD40L表达与C反应蛋白(CRP)水平正相关(r=0.553,P<0.05)。结论:CD40L异常表达在川崎病发病机制中其起重要作用。静脉输注丙球能下调CD40L表达,且有利于治疗血管炎。     

氧化应激介导的Ras-ERK信号通路活化参与醛固酮诱导的肾小球系膜细胞增殖

目的 探讨氧化应激介导的Ras-胞外信号调节激酶(ERK1/2)信号通路活化在醛同酮( ALDO)诱导的系膜细胞增殖中的作用.方法 体外培养人肾小球系膜细胞,应用3H-胸腺嘧啶(3H-TdR)掺入法和细胞计数测定系膜细胞增殖;Western印迹检测Ki-RasA、c-Raf、MEK1/2和ERK1/2活化.结果 ALDO可显著促进系膜细胞增殖,抗氧化剂乙酰半胱氨酸(NAC)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)显著抑制ALDO诱导的系膜细胞增殖(均P＜ 0.01).ALDO刺激系膜细胞3h,活化的Ki-RasA、c-Raf、MEK1/2和ERK1/2表达显著增强,分别是对照组的4.05倍、3.62倍、4.52倍和3.40倍(均P＜0.01).抗氧化剂NAC几乎完全阻断ALDO诱导的Ki-RasA、c-Raf、MEK1/2和ERK 1/2活化(均P＜0.01).Ki-RasA siRNA可呈浓度依赖性降低系膜细胞Ki-RasA表达,并显著抑制ALDO诱导的Ki-RasA活化及系膜细胞增殖(P＜0.01).c-Raf抑制剂GW5074和MEK1/2抑制剂PD98059亦显著抑制ALDO诱导的系膜细胞增殖,其抑制率均达到65％(P＜0.01).Ki- RasA siRNA不能降低ALDO诱导的磷酸肌醇-3激酶( PI3K)磷酸化.联合应用PI3K抑制剂LY294002和MEKl/2抑制剂PD98059可完全阻断ALDO诱导的系膜细胞增殖(P＜0.01).结论 ALDO可通过氧化应激活化Ki-RasA-c-Raf-MEK-ERK信号通路.同时阻断ERK1/2和PI3K信号通路可完全抑制ALDO诱导的系膜细胞增殖.