叶任高教授治疗肾病综合症经验

目前治疗原发性肾病综合症（肾综）的主要药物是肾上腺皮质激素（激素），但长期使用可引起不良反应，如诱发或加重感染、神经精神症状。笔者有幸跟随叶老进修（卫生部全国高肾班），目睹其治疗肾综在激素治疗的不同阶段配合使用中药，无论在提高疗效或减少激素副作用均有...     

系统性红斑狼疮临床分析及其预后判断

系统性红斑狼疮 (SL E)是一累及全身多个系统的自身免疫性疾病 ,约半数患者有临床狼疮性肾炎 (L N) ,肾活检几乎所有SL E患者均有不同程度肾脏损害 ,晚期表现为高血压及肾功能不全。因此 ,对 L N的早期诊断 ,早期治疗具有非常重要的意义。1　资料和方法1.1　病例选择　入选病例必须符合下列条件 :1符合美国风湿病协会定义的 SL E诊断标准 (1982年 ) ;2肾活检符合 L N病理组织学改变。1.2　观察指标　按照改良的 Austin方法将狼疮性肾炎病理形态学改变分为急性指标 (AI)和慢性指标 (CI) ,并以半定量计分0、1、2、3分别代表阴性、轻微…     

肾脏病尿微量蛋白测定的临床意义

我们用RIA测定了小儿肾脏病37例尿β_2M、THP、ALB、IgG、SIgA结果,并与对照组比较,现报道如下: 1 对象和方法 1.1 正常对照组 11例经尿分析筛查示正常的儿童,男7例,女4例,年龄(7.4±3.4)岁。 1.2 急性肾炎组 19例,男12例,女7例,年龄(8.2±3.3)岁。均有不同程度的尿少、水肿及血尿,全部病例ASO阳性,血沉增快,补体C_3降低,均符合小儿链球菌感染后急性肾小球肾炎诊断标准。 1.3 肾病综合征组 18例,男13例,女5例,年龄(5.1±3.6)岁,均符合肾病综合征诊断标准。 1.4 检测方法 均于入院1周内留12小时防腐尿,测定尿β_2-M,THP、ALB、IgG、SIgA。β_2M,ALB、SIgA放免试剂盒由上海放免分析技术研究所提供,IgG、THP试剂盒由北京原子能研究所提供,     

以消化道症状首发伴双肾积水输尿管扩张的儿童狼疮性肾炎1例

儿童系统性红斑狼疮(SLE)首发表现为消化道症状比较少见,而合并双肾输尿管积水的更加少见,尤其是儿童患者更是鲜见报道,现就本科收治1例儿童狼疮性肾炎报道如下     

核心蛋白聚糖抑制转化生长因子β1诱导的人肾小管上皮细胞转分化机制研究

目的 研究核心蛋白聚糖抑制转化生长因子β1(TGF-β1)诱导的人肾小管上皮细胞-间充质细胞-转分化(EMT)的机制.方法 将体外培养的人肾小管上皮细胞(HK-2)分为4组:(1)阴性对照组;(2)100 ng/ml核心蛋白聚糖组;(3)10 ng/ml TGF-β1组;(4)100 ng/ml核心蛋白聚糖和10ng/ml TGF-β1组.Western blot法检测信号通路ERK、PI3K、Smad_3的磷酸化水平和β-catenin的蛋白水平;实时定量-PCR检测snail mRNA的表达情况,逆转录-PCR检测淋巴细胞增长因子1(LEF-1)mRNA的表达情况.结果 (1)与对照组相比,TGF-β1诱导组ERK(1.11 ±0.09:0.47 ±0.07)、PI3K(14.79 ±1.02:2.48 ±0.06)、Smad_3(0.95 ±0.02:0.08 ±0.01)的磷酸化水平明显增高,snail(2.59±0.70:1.02±0.13)、LEF-1(1.85 ±0.08:0.30 ±0.11)的mRNA的表达量明显增高,β-catenin(1.46 ±0.20:0.49±0.05)的最明显增高;(2)单纯核心蛋白聚糖组与对照组相比,所得结果 差异均无统计学意义.核心蛋白聚糖和TGF-β1共同刺激组与TGF-β1组相比,ERK(0.58 ±0.08)的磷酸化水平及snail mRNA(1.24 ±0.03)的表达量明显降低而PI3K(15.84 ±1.64),Smad_3(0.90 ±0.04)的磷酸化水平,LEF-1的mRNA(1.64 ±0.07)、β-catenin(1.42±0.09)的量差异无统计学意义.结论 核心蛋白聚糖抑制TGF-β1诱导的人肾小管上皮细胞EMT可能是通过阻止ERK信号转导通路实现的.     

肾组织中核心蛋白聚糖的表达和定位及其与肾间质损害的关系

目的：观察核心蛋白聚糖在小儿肾脏病肾活检组织中的定位及表达，并探讨其与肾小管间质损害程度及转化生长因子-β1（TGF-β1）之间的关系。方法：收集36例肾脏疾病患儿肾活检病理及临床资料，对其肾小管间质损害程度进行分组，应用免疫组织化学方法检测核心蛋白聚糖和TGF-β1，在肾间质内的定位及表达。结果：核心蛋白聚糖主要表达于肾小管上皮细胞，近曲小管表达比远曲小管更为明显，随着肾间质损害程度的加重，核心蛋白聚糖的表达量逐渐增加。TGF-β1的表达亦主要见于肾小管上皮细胞，在近曲小管和远曲小管之间无明显的差异，TGF-β1的表达量也随着肾小管间质损害程度的加重而增加。肾间质中，核心蛋白聚糖和TGF-β1两者表达量呈正相关。结论：核心蛋白聚糖可能作为反映肾问质损害程度的一个标志性蛋白，同时对TGF-β1的表达起一定的抑制作用。     

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.     

小儿川崎病CD4+T细胞CD40L和E-选择素的表达

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（sCD40L） 及E-选择素.结果：川崎病患儿CD4^＋T细胞表面CD40L表达及血清中E-选择素显著高于其他发热性疾病对照组及正常儿童对照组（P＜0.01）,川崎病患儿静脉输注丙球治疗后明显下降（P＜0.01）.CD4^＋T细胞表面CD40L表达及E-选择素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与冠状动脉损伤无明显相关性.川崎病患儿CD4^＋T细胞表面CD40L表达与E-选择素水平正相关（r=0.626,P＜0.05）.结论：CD40L异常表达及血清中E-选择素在川崎病发病机制中起重要作用.静脉输注丙球能下调CD40L表达及血清中E-选择素,且有利于治疗血管炎.     

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.     

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.