亚慢性砷暴露对大鼠肾脏功能和形态的影响

目的观察亚慢性亚砷酸钠暴露对大鼠肾脏结构和功能的影响。方法 27只雄性SD大鼠,随机分对照组,砷暴露低剂量组和砷暴露高剂量组,分别自由饮用去离子水和亚砷酸钠水溶液,时间为3个月。观察肾脏组织,采用全自动生化分析仪检测肾功,苏木精-伊红染色（HE染色）检测组织病理学改变,电镜观察超微结构改变。结果①生化分析发现尿素氮和葡萄糖水平随染毒剂量增加而显著增加。②HE染色镜检发现砷暴露组大鼠肾小管发生空泡样变、嗜酸性变,损伤效应具有剂量依赖性,且发现有炎性细胞的浸润。③电镜检查发现砷暴露组大鼠肾小球有轻度的系膜增生。结论亚慢性饮水染砷可对肾脏功能产生显著影响,导致肾小球系膜轻度增生和肾小球空泡样变。     

福辛普利对大鼠肾小球系膜细胞增殖及转化生长因子β1表达的影响

目的观察新型血管紧张素转化酶抑制剂（angiotension—converting enzyme inhibitor，ACED——福辛普利（fosinopril，FOS）对脂多糖（lipopolysaccharide，LPS）诱导的大鼠肾小球系膜细胞（glomerular mesangial cell，GMC）增殖及转化生长因子（transforming growth factor，TGF）β1表达的影响。方法建立体外培养大鼠肾小球系膜细胞，鉴定后3～10代用于实验。实验分为5组：对照组（Ctrl组）、脂多糖刺激组（LPS组）、福辛普利高、中、低剂量组（分别为FOS1组、FOS2组和FOS3组），分别于24h和48h两个时间点甲基噻唑基四唑（methyl thiazolyl tetrazolium，MTT）比色法测定各组细胞增殖情况；于6h，12h，24h后酶联免疫测定（enzyme—linked immunosorbent—assay，ELISA）法测定细胞培养上清液中转化生长因子β1蛋白的表达量，荧光半定量RT～PCR法检测转化生长因子β1mRNA表达的变化。结果脂多糖可诱导大鼠肾小球系膜细胞增殖，福辛普利可抑制脂多糖诱导的大鼠肾小球系膜细胞增殖；正常培养的大鼠肾小球系膜细胞均有一定量的转化生长因子β1蛋白分泌和mRNA表达；LPS组在各时间点转化生长因子β1蛋白分泌和mRNA表达均高于Ctrl组（P〈0．01），而FOS1组、FOS2组、FOS3组转化生长因子β1蛋白分泌和mRNA表达均低于LPS组（P〈0．01）。结论脂多糖可诱导大鼠肾小球系膜细胞增殖。福辛普利可抑制脂多糖诱导的大鼠肾小球系膜细胞增殖。福辛普利能够从蛋白水平和mRNA水平抑制脂多糖诱导的大鼠肾小球系膜细胞转化生长因子β1的表达，为福辛普利的肾脏保护作用提供理论依据。     

肾脏原发系统性轻链型淀粉样变患者的临床特征和生存分析

目的 总结肾脏原发系统性轻链型淀粉样变患者的临床病理特征,探讨影响预后的因素.方法 回顾性分析25例肾脏原发系统性轻链型淀粉样变患者的临床资料,随访其生存情况.结果 25例肾脏原发系统性轻链型淀粉样变患者,中位年龄57(37～69)岁,游离λ轻链型占绝大多数(88%,22/25).突出症状为大量蛋白尿、肾病综合征伴顽固性水肿,尿蛋白排泄以白蛋白为主.肾脏病理病变主要累及肾小球系膜区局灶性或弥漫性无细胞性明显增宽.25例患者诊断后中位生存时间24.4个月,1、2和3年总生存率分别为(65±10)%、(46±12)%和(15±12)%.明确诊断时单独肾脏淀粉样变14例,淀粉样变同时累及其他脏器组织11例,两者诊断后中位生存时间分别为24.7个月和16.4个月,差异有统计学意义(P=0.03).Cox回归单因素分析表明:年龄、性别、骨髑浆细胞比例、白蛋白和血红蛋白水平与预后无关(P＞0.05),肾功能损害和淀粉样变同时累及其他脏器与预后相关(P＜0.05),其中同时有心脏病变很可能与预后呈负相关(P=0.06),进一步Cox逐步回归多因素分析表明肾功能损害是影响肾脏原发系统性轻链型淀粉样变患者预后的一个独立危险因素(P＜0.05).结论 肾功能损害是影响预后的独立高危因素,同时联合有其他脏器尤其是心脏淀粉样变患者预后差.     

Follow-up of two patients with mesangial IgA glomerulonephritis exposed to cadmium and organic solvents

For several years we carried out a follow-up of two patients with IgA mesangial glomerulonephritis with antecedents of exposure to toxic substances (cadmium and organic solvents). The first case involved a 47 year old male who was diagnosed with mesangial IgA glomerulonephritis eight years ago; he had been working for twelve years as a solderer. He had used metal bars containing 25% cadmium as part of the soldering material. Very high levels of cadmium were detected in his blood and urine. The second case involved a 50 year male who was exposed to a wide number of organic dissolvents for 23 years. Three years ago he was diagnosed with a proliferative diffuse mesangial glomerulonephritis with IgA deposits; in spite of that, the patient continued working until one year ago, when was found to have a chronic stage 3 renal disease secondary to IgA nephropathy. Patients diagnosed with mesangial IgA glomerulonephritis should be kept apart from exposure to nephrotoxic substances.     

肾血管病变在IgA肾病病理中的意义

目的 探讨肾血管病变与肾小球病理改变之间的关系。方法 回顾性分析肾活检病例1833例,其中IgA肾病1093例,非IgA肾病740例。采用方差检验对各组资料进行统计分析。结果在1093例IgA肾病中有肾血管病变者426例,占39％,在740例非IgA肾病中存在肾血管病变者为182例占25％,两者有显著性差异（P〈0．01）。在IgA肾病的肾血管病变中,主要是以肾小动脉内膜增厚、纤维化及管腔狭窄病变为主。IgA肾病各亚型中存在肾血管病变的分布为：轻微病变型22．5％（36／160）,局灶节段增生型41％（195／476）,系膜增生型39．1％（135／345）,硬化型93．1（27／29）。此分布的不同具有显著性差异（P〈0．01）。结论IgA肾病通常会伴有多种肾间质血管病变,并且血管病变与IgA肾病的病理改变及临床特点密切相关,提示肾血管病变是影响IgA肾病发展的重要因素。     

Purple corn anthocyanins retard diabetes-associated glomerulosclerosis in mesangial cells and db/db mice

Purpose

Diabetic glomerulosclerosis is the hardening of the renal glomeruli that can lead to kidney failure. In the early stage of glomerulosclerosis occur renal mesangial expansion and renal filtration dysfunction. Purple corn has been classified as a functional food and is rich in anthocyanins exerting potential disease-preventive activities. The in vitro study using human renal mesangial cells examined that anthocyanin-rich purple corn butanol fraction (PCB) can attenuate high glucose (HG)-promoted mesangial cell proliferation and matrix accumulation.

Methods

Cells were cultured for 3?days in media containing 33?mM glucose in the presence of 1–20?μg/mL PCB. In the in vivo animal study, db/db mice were treated with 10?mg/kg anthocyanin-rich polyphenolic extracts of purple corn (PCE) for 8?weeks.

Results

HG enhanced mesangial production of the fibrosis biomarkers of collagen IV and connective tissue growth factor (CTGF), which was markedly attenuated by adding PCB. Such mesangial fibrosis entailed interleukin-8 activation via eliciting Tyk2-STAT signaling pathway. PCB dampened HG-promoted mesangial hyperplasia that appeared to be attributed to increased expression of platelet-derived growth factor. The 8-week administration of PCE lowered plasma glucose level of db/db mice and ameliorated severe albuminuria. Moreover, PCE lessened collagen fiber accumulation in kidney glomeruli and CTGF expression via retarding TGF-β signaling. Protein expressions of nephrin and podocin, key proteins for filtration barrier function of the glomerular capillary wall, were repressed by treating mice with PCE.

Conclusion

Purple corn may be a potent therapeutic agent for the treatment for diabetes-associated glomerulosclerosis accompanying proteinuria and kidney filtration dysfunction.     

成人肾小球疾病199例临床病理分析

目的：探讨成人肾小球疾病的病理类型及其特点。方法：回顾性分析199例成人肾小球疾病患者的年龄性别分布、肾脏病理类型及其与临床表现的关系。结果：199例患者中，原发性肾小球疾病占72．9％，继发性肾小球疾病占27．1％；原发性肾小球疾病病理类型以IgA肾病（IgAN）为主，占34．5％，膜性肾病（MN）占11．0％，微小病变（MCD）占5．5％．系膜增生性肾小球肾炎（MsPGN）占29．7％，毛细血管内增生性肾小球肾炎（EnPGN）占2．8％，局灶增生性肾小球肾炎（FPGN）占5．5％．增生硬化性肾小球肾炎占（PSGN）3．4％，新月体肾小球肾炎占（CreGN）1．4％，局灶节段性肾小球硬化（FSGS）占4．1％。继发性肾小球肾炎中以狼疮性肾炎（LN）为主，占59．3％，乙型肝炎相关性肾炎占9．3％．过敏性紫癜肾炎占22．2％．多发性骨髓瘤占1．9％，肾淀粉样变占3．7％，糖尿病肾病占3．7％。临床表现无症状尿检异常占18．6％．肾病综合征占40．7％，急性肾衰竭占1．5％，慢性肾衰竭占4．5％，急进性肾炎占1-5％，肾炎综合征占33．2％。结论：原发性肾小球疾病是成人最常见肾小球疾病，以IgAN为主，高发年龄在青壮年，继发性肾小球疾病中以LN多见，女性多发，其他继发性肾小球疾病逐渐增多。     

P16^INK4a在原发性系膜增生性肾小球肾炎的表达及临床意义

目的探讨原发性系膜增生性肾小球肾炎活检肾组织（MsPGN）细胞周期素依赖蛋白激酶抑制剂P16^INK4a在肾组织的表达及其与固有细胞增生、硬化的关系,结合临床参数分析,为延缓慢性肾脏病进展开辟新的途径。方法采用非生物素免疫组化二步法检测36例MsPGN患者肾活检组织和6例外伤肾切除石蜡包埋肾组织中肾小球和肾小管间质P16^INK4a的表达水平,并结合临床资料进行分析。结果（1）MsPGN组肾小球和小管间质P16^INK4a表达升高,与对照组相比,差异有统计学意义（P〈0．01）。36例中15例硬化、新月体形成组肾小球上高表达,而非硬化、非新月体形成组肾小球上仅部分表达,组间相比差异有统计学意义（P〈0．01）,小管间质表达差异无统计学意义（P〉0．05）。（2）36例MsPGN组中肾小球P16^INK4a表达与未使用类固醇激素／免疫抑制剂、未使用ACEI／ARB正相关（r=0．774、0．497,P〈0．01）,BP、Scr水平与P16^INK4a呈正相关（r=0．64、0．473,P〈0．01）,Ccr、TMP与P16^INK4a呈负相关（r=-0．487、-0．694,P〈0．01）,而小管间质表达与临床资料不相关。结论P16^INK4a可能起促进异常增殖的肾固有细胞消退作用,并诱导肾脏衰老导致肾小球硬化、新月体形成;P16^INK4a表达不仅反映肾功能损伤程度,也间接反映BP和蛋白尿水平;药物干预可影响P16^INK4a的表达。     

多种菌外膜蛋白诱导新IgAN模型的肾肝脾病理组织学分析

目的分析三种IgA肾病模型所造成的肾肝脾损伤并加以比较,以从中选出一种理想的IsA肾病模型,并为今后模型的药物治疗提供指导依据。方法用HE染色,刚果红染色,偏振光显微镜观察金葡菌组、葡聚糖组和大肠杆菌外膜蛋白组肾肝脾的病理学改变。结果大肠杆菌外膜蛋白组肾小球的系膜细胞和系膜基质无增生等改变,肝脾损伤严重,部分可见粉红物质沉积。葡聚糖组个别肾小球的系膜细胞局灶性的轻度增生,肝脾血管内粉染物质沉积严重。金葡菌组多数肾小球系膜细胞和系膜基质不同程度的增生,肝肾损伤轻。结论金葡菌组更接近于人的IgA肾病,造模效果优于大肠杆菌外膜蛋白和葡聚糖。     

Chronic overexposure to cadmium fumes associated with IgA mesangial glomerulonephritis

BACKGROUND: Cadmium is a metal used in the zinc, copper and steel industries, and in the manufacture of electric batteries and solar cells. Acute cadmium poisoning is characterized by irritation of the respiratory tract, while in chronic poisoning the main target organ is the renal tubule. AIMS: We report a patient with chronic work overexposure to cadmium, who presented a IgA mesangial glomerulonephritis with no respiratory or renal tubule involvement. Case report A 39-year-old patient was referred to our hospital for evaluation of a glomerular nephropathy. For the past 12 years he had worked as a welder, using cadmium electrodes. The patient had no respiratory symptoms and the chest X-ray was normal. Tests showed a proteinuria of 2 g in 24 h with microhaematuria [150 red blood cells/high power field (rbc/hpf)], with preservation of the renal function (creatinine clearance of 137 ml/min). The concentrations of cadmium in blood and urine were 45 micro g/l and 25 micro g/g creatinine, and an environmental study showed that levels of cadmium in the workplace were 52 micro g/m(3). A renal biopsy showed an IgA mesangial glomerulonephritis. The patient ceased to work with cadmium, and 1 year later cadmium levels had decreased and renal function was found to be stable. CONCLUSIONS: IgA mesangial glomerulonephritis is a disease of unknown aetiology which has been associated with other diseases. Chronic overexposure to cadmium may contribute to the development of this nephrophathy.     

共轭亚油酸异构体的抗乳腺癌活性研究

目的 :　研究共轭亚油酸 (CLA)两种主要异构体 (9,1 1 - CLA和 1 0 ,1 2 - CLA)对两种人乳腺癌细胞 (MCF- 7,MDA- MB- 2 31 )和大鼠扩散乳腺癌细胞 (F3 )活性的异同。方法 :　采用MTT方法研究两种主要 CLA异构体在不同浓度、不同作用时间及不同给药方式下 ,抑制上述几种癌细胞增殖的能力。结果 :　 1 0 ,1 2 - CLA对所有的试验癌细胞均呈现较强的抑制活性 ,而 9,1 1 -CLA仅对 MCF- 7呈现抑制活性 ,对 MDA- MB- 2 31和 F3 基本无活性 ;1 0 ,1 2 - CLA对 F3 的抑制活性与处理时间和给药方式密切相关 ,加药后不更换培养液处理 72 h可使其抑制能力达到最大值 ;细胞周期研究显示 1 0 ,1 2 - CLA对 MCF- 7呈微弱的 G0 / G1期抑制 ,而对 F3 细胞周期则无影响。结论 :　 CLA的两种主要异构体在该实验条件下对上述三种癌细胞增殖抑制能力和作用机制有着明显的差异 ,其中 1 0 ,1 2 - CLA活性明显强于 9,1 1 - CLA。 1 0 ,1 2 - CLA是通过其代谢物对 F3 的增殖起抑制作用     

Biochemical vitamin B6 deficiency in adults with chronic glomerulonephritides with and without the nephrotic syndrome

Thirty four patients suffering from chronic glomerulonephritides with and without the nephrotic syndrome and with an average age of 35 years were studied. Twenty eight of the patients underwent renal biopsy, as part of their management, and the histological classification was as follows: 7 membranous glomerulonephritis, 3 proliferative glomerulonephritis, 11 mesangiocapillary glomerulonephritis, 2 minimal change disease, 2 mesangial proliferative and 3 diffuse proliferative glomerulonephritis. Fourteen of the patients were on therapeutic diets mainly high protein - low salt and low cholesterol. Eighty three per cent of these patients were found to be biochemically deficient in vitamin B6 as judged by plasma pyridoxal-5-phosphate levels. No correlations were found between vitamin B6 and serum albumin, histological type of renal disease, duration of illness or serum cholesterol. By contrast, none of the patients with histologically similar disease that were daily receiving 25mg pyridoxine orally at the time of study were deficient. The importance of vitamin B6 deficiency in the nephrotic syndrome is discussed and it would appear that supplementary vitamin B6 should form part of the overall management of these patients.     

弥漫性系膜增生伴局灶节段性肾小球硬化大鼠模型的建立

目的：建立弥漫性系膜增生伴局灶节段性肾小球硬化动物模型。方法：对SD大白鼠行腹部部正中切口右肾摘除术，术后7d,30d分别尾静脉注射阿霉素4mg/kg,3mg/kg，第70d制成模型，结果：该模型临床上表现为高度浮肿，大量蛋白尿、低蛋白血症、高脂血症及肾功能损害；病理学检查，计算机图象分析及免疫组织化学染色显示，肾小球主要表现为系膜基质弥漫性中至重度增生，系膜细胞轻度增生，其中约22％的肾小球出现节段性硬化，纤维化生长因子血不板源性生长因子－B（PDGF－B）和成纤维细胞生长因子－b(bFGF)的表这均增加，表明肾小球正处于由增生向硬化转化转化的过渡阶段。结论：本模型的建立为实验研究肾小球疾病由系膜增生向硬化转化的机制及防治措施创造了条件。     

New treatments for renal carcinoma

Renal cell carcinoma presents several unique features, which distinguish it from other tumours. The increase in survival that has been described in patients with renal cell carcinoma following nephrectomy breaks a classical rule of oncology, which states that surgery of the primary tumour has no role in the treatment of patients with advanced disease. Together with melanoma, it is the only tumour in which immunomodulatory treatments with drugs such as interleukin-2 produces a clinical benefit to patients. In randomized trials treatment of metastatic renal cell carcinoma with high dose interleukin-2 has confirmed its ability to induce long-term complete responses, which in practice can be considered equivalent to cure. Lastly, renal cell carcinoma is being used as a clinical model to demonstrate the role of several targeted treatments, with over 30 novel agents under development. It has been the first tumour type in which treatment with angiogenesis inhibitors has shown a clinical benefit. This article reviews the most relevant aspects of renal cell carcinoma, including epidemiology, prognostic factors, clinical presentation, molecular bases and the current status of development of the most relevant novel treatments for this disease.     

Are organohalogen contaminants a cofactor in the development of renal lesions in east Greenland polar bears (Ursus maritimus)?

Tissues of polar bears (Ursus maritimus) from East Greenland contain the highest concentrations of organohalogen contaminants (OHCs) among subpopulations of any mammalian species in the Arctic. Negative associations also have been found between OHC concentrations and bone mineral density and liver histology parameters for this subpopulation of polar bears. The present study examined the OHC concentrations and adverse effects on renal tissue for 75 polar bears collected during 1999 to 2002. Specific lesions were diffuse glomerular capillary wall thickening, mesangial glomerular deposits, tubular epithelial cell hyperplasia, hyalinization of the tubular basement membrane, tubular dilatation, atrophy and necrosis, tubular medullary hyalin casts, interstitial fibrosis, and mononuclear cell infiltration. With the exception of mononuclear cell infiltrations, all these parameters were correlated with age, whereas none was associated with the sex of the animals. In an age-controlled statistical analysis of covariance, increases in glomerular mesangial deposits and interstitial fibrosis were significantly (p < 0.05) correlated with polybrominated diphenyl ether (sigmaPBDE) concentrations in subadults. In adult males, statistically significant (p < 0.05) positive correlations were found for tubular epithelial cell hyperplasia and dieldrin concentration; diffuse glomerular capillary wall thickening and chlordane (sigmaCHL) concentrations, and tubular medullary hyalin casts and sigmaCHL, sigmaPBDE, polychlorinated biphenyl, and hexachlorocyclohexane concentrations. The lesions were consistent with those reported previously in highly OHC-contaminated Baltic seal populations and exposed laboratory animals. The renal lesions were a result of aging. However, based on the above statistical findings as well as the nature of the findings, we suggest that long-term exposure to OHCs may be a cofactor in renal lesion occurrence, although other cofactors, such as exposure to heavy metals and recurrent infections from microorganisms, cannot be ruled out. This is new and important knowledge in the assessment of health status among wildlife populations and humans relying on food resources that are contaminated with OHCs.     

Kidney biopsy in the hepatosplenic form of infection with Schistosoma mansoni in man

A study of early glomerular lesions was made in 8 patients infected with Schistosoma mansoni but having no clinical evidence of renal disease. Electron-microscopy of renal biopsies showed the presence of electron-dense deposits in basement membranes and of laminated bodies near the mesangial cells. Immunofluorescence showed that the deposits corresponded to IgG in 8 cases and to IgM in 2 cases. These lesions are comparable with those found in the kidneys of patients with cirrhosis of the liver.     

肿瘤患者深部真菌医院感染现状调查

目的 调查肿瘤患者深部真菌医院感染现状，以制定有效的防治措施。方法 收集本院246例肿瘤患者的临床资料及真菌培养结果，加以统计和分析。结果 246例感染部位以下呼吸道为主(46．9％)，泌尿道次之(21．4％)，246例患者标本共培养出真菌246株，以白色假丝酵母菌占第1位(58．1％)，热带假丝酵母菌占第2位(24．8％)。结论 本组病例发生真菌医院感染的病因与原发肿瘤疾病、年龄、手术及放射疗法、免疫抑制剂和激素、抗代谢药物的使用、抗生素的使用及住院期间侵入性操作等危险因素密切相关。     

姜黄素通过上调miR-637抑制肾癌786-O细胞的增殖、迁移和侵袭

目的 探讨姜黄素对肾癌786-O细胞的增殖、迁移和侵袭的影响及其可能的分子机制。方法 体外培养人正常肾小管上皮细胞HK-2和肾癌786-O细胞,将786-O细胞分为对照组、低剂量姜黄素组、中剂量姜黄素组、高剂量姜黄素组、miR-NC组、miR-637组、高剂量姜黄素+anti-miR-NC组、高剂量姜黄素+anti-miR-637组。分别进行实时荧光定量PCR（qRT-PCR）、MTT、Transwell和蛋白质印迹（Western blot）实验来检测各组的miR-637表达量、细胞活力、迁移侵袭能力和相关蛋白表达水平。结果 与人正常肾小管上皮细胞HK-2比较,肾癌786-O细胞中miR-637的表达水平降低（P<0.05）。与对照组比较,中、高剂量姜黄素组786-O细胞的活力、迁移和侵袭细胞数、CyclinD1、MMP-2及MMP-9表达水平均显著降低,p21表达显著升高,miR-637的表达水平均显著升高（均P<0.05）。与miR-NC组比较, miR-637组的miR-637表达水平提高,miR-637组的细胞活力、迁移和侵袭细胞数、CyclinD1、MMP-2和MMP-9表达均显著降低,p21表达升高（均P<0.001）。与高剂量姜黄素+anti-miR-NC组比较,高剂量姜黄素+anti-miR-637组的miR-637表达水平降低,786-O细胞的活力、迁移和侵袭细胞数、CyclinD1、MMP-2和MMP-9表达均升高,p21表达降低（均P<0.05）。结论 姜黄素可能通过上调miR-637发挥肾癌抑制作用。     

全反式维甲酸对糖尿病大鼠肾小管-间质TGF—β1和α-SMA表达的影响

目的探讨全反式维甲酸对糖尿病大鼠肾小管-间质转化生长因子α（TGF—β1）、d平滑肌肌动蛋白（α—SMA）表达的影响。方法24只链脲佐菌素（STZ）诱导的糖尿病大鼠随机分为治疗组（T），模型组（D）各12只，12只正常组（N），T组给予全反式维甲酸20mg／（kg·d）油溶液灌胃，D组和N组分别灌等量的植物油。4、8周每组各处死大鼠6只，测量尿微量白蛋白排泄率、肾重／体重、血肌酐（Scr）、血糖。肾组织PAS、Masson染色。免疫组化方法检测肾小管-间质TGF—β1、α—SMA表达。结果全反式维甲酸可减轻肾小球系膜区基质、细胞的增生，明显缓解肾小管的损伤，肾间质的基质减少。4周尿微量白蛋白的排泄率实验组低于模型组[（3．08±0．48）μg／minVS（3．35±0．56）μg／min，P〈0．05]，8周时尿微量白蛋白的排泄率明显低于同期模型组[（2．49±0．40）μg／minVS（4．53±0．87）μg／min，P〈0．01]；肾小管-间质TGF-β1、α—SMA表达明显低于模型组（P〈0．01）。结论全反式维甲酸可减轻糖尿病大鼠肾小管-间质的损害，减少尿蛋白。可能通过下调肾小管-间质TGF—β1表达、减少肾小管-间质肌成纤维细胞的数量，防止肾间质的纤维化，保护肾功能。