类风湿性关节炎肾损害的组织病理改变——附4例报告及文献复习

目的　探讨类风湿性关节炎 (RA)肾损害的组织病理学改变特点。方法　总结 4例RA肾损害的临床病理资料 ,并结合文献进行分析。结果　 4例均呈蛋白尿伴血尿 ,其中 3例肾功能不全 ,组织病理为IgA肾病 2例、节段系膜增生性肾炎及局灶节段性肾小球硬化各 1例 ,文献报道临床表现以蛋白尿、血尿为主 ,可呈肾病综合征或伴肾功能不全 ,病理类型以系膜增生性肾炎 (包括IgA肾病 )、膜性肾病和肾淀粉样变性多见。结论　类风湿性关节炎的组织病理学改变以系膜增生性肾炎最常见 ,临床表现多样化     

类风湿性关节炎肾损害的组织病理改变--附4例报告及文献复习

目的探讨类风湿性关节炎(RA)肾损害的组织病理学改变特点. 方法总结4例RA肾损害的临床病理资料,并结合文献进行分析.结果 4例均呈蛋白尿伴血尿,其中3例肾功能不全,组织病理为IgA肾病2例、节段系膜增生性肾炎及局灶节段性肾小球硬化各1例,文献报道临床表现以蛋白尿、血尿为主,可呈肾病综合征或伴肾功能不全,病理类型以系膜增生性肾炎(包括IgA肾病)、膜性肾病和肾淀粉样变性多见.结论类风湿性关节炎的组织病理学改变以系膜增生性肾炎最常见,临床表现多样化.     

微小病变肾病患者尿层粘连蛋白的变化及临床意义

本文探讨尿层粘连蛋白（laminin）在微小病变肾病中的变化及临床意义。将72例肾病综合征患者分实验1组（微小病变肾病26例）、实验2组（系膜增生性肾炎16例、膜增生性肾炎13例、膜性肾病9例和局灶节段性肾小球硬化8例），对照组30例，用放免分析法对尿laminin进行检测。结果显示，尿laminin水平在微小病变肾病中无明显增高，该检测可能成为微小病变肾病临床诊断和治疗实验室指标之一。     

实用临床诊疗规范——肾脏内科疾病(二)

肾病综合征1概述肾病综合征是肾小球疾病的常见表现,包括了因多种肾脏病理损害导致的严重蛋白尿及相应的临床表现,最基本特征是大量蛋白尿(≥3·5 g/d)及低白蛋白血症(≤30 g/L),并常伴有水肿和(或)高脂血症。肾病综合征按病因可分为原发性、继发性和遗传性3大类,可由不同病理类型的肾小球疾病引起,见表1。表1肾病综合征的分类和常见病因分类儿童青少年中老年原发性微小病变性肾病系膜增生性肾小球肾炎膜性肾病系膜毛细血管性肾小球肾炎局灶性节段性肾小球硬化继发性过敏性紫癜肾炎系统性红斑狼疮肾炎糖尿病肾病乙型肝炎相关性肾过敏性紫癜…     

IgA肾病与乙型肝炎病毒感染的相关分析

目的探讨IgA肾病与乙型肝炎病毒感染的相关性。方法选择2010年6月-2016年6月在医院确诊的IgA肾病患者103例为IgA肾病组,另选择同期在医院治疗的非IgA肾病患者110例为对照组;检测患者血清及肾组织HBV携带率,分析IgA肾病患者不同临床分级、不同病理类型、不同间质炎症分级中HBV携带情况。结果 IgA肾病组血清及肾组织中HBV携带率均高于对照组(P0.05);临床分级为Ⅳ~Ⅴ级的患者HBV携带率较高,与Ⅰ~Ⅲ级比较,差异有统计学意义(P0.05);系膜增生性肾炎伴局灶节段性硬化组HBV携带率高,与非系膜增生性肾炎伴局灶节段性硬化组比较差异有统计学意义(P0.05);间质炎症分级为(++++)的患者HBAg阳性率显著高于其他间质炎症分级(P0.05)。结论 IgA肾病与乙型肝炎病毒感染具有一定的关系,且临床分级高、系膜增生性肾炎伴局灶节段性硬化以及间质炎症分级高患者HBV携带率高。     

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。     

单核细胞趋化蛋白-1在系膜增生性肾小球肾炎中的表达

目的用免疫组化的方法来分析单核细胞趋化蛋白-1在系膜增生性肾小球肾炎中表达的变化规律,揭示单核细胞趋化蛋白-1是否可做为病理条件下系膜细胞增生程度评判的一项指标。方法应用链霉素抗卵白素一过氧化酶连接法（S—P法）检测正常肾组织、42例轻至重度系膜增生性肾小球肾炎肾组织标本肾小球区单核细胞趋化蛋白-1表达的相对面积的变化。利用HPIAS—1000采集的图像对肾小球区的阳性表达区域所占相对面积进行测算。结果在正常肾组织切片中,仅部分肾小球内系膜细胞、肾小管上皮细胞及灶件炎细胞浸润区域单核细胞趋化蛋白-1阳性表达,绝大多数没有表达,染色阴性。不同程度增生肾小球区单核细胞趋化蛋白-1表达的相对面积不同,单核细胞趋化蛋白-1阳性表达的相对面积随系膜增生病变程度加重而增加,存在统计学差异。结论单核细胞趋化蛋白-1在肾小球区的表达随系膜增生病变程度加重而增加。在不同病变程度系膜增生性肾小球肾炎的肾小管、间质存在强、弱不等的表达。正常肾组织中,仅有少量单核细胞趋化蛋白-1表达。     

肾小动脉增厚在IgA肾病中的意义

目的 观察肾小动脉增厚在IgA肾病中的意义。方法 将78例IgA肾病分为观察组（伴有肾小动脉增厚）和对照组（不伴有肾小动脉增厚），并分析其临床及病理特点。结果 观察组的肾功能不全明显高于对照组，观察组病理类型表现为局灶增生硬化性肾小球肾炎及膜增殖性肾小球肾炎，观察组的病理特点表现为系膜中度增生、肾小球节段硬化、肾小球硬化20％、肾缺血改变、新月体形成、血管洋葱皮样改变、球囊粘连、肾间质纤维化明显高于对照组。结论 肾小动脉硬化在肾功能不全的发病中占重要的地位，参与膜增殖性肾小球肾炎及局灶节段硬化性肾小球肾炎的发病及形成，与IgA肾病的预后呈相关关系。     

IgA肾炎治疗进展

IgA肾炎（IgAN）是肾小球系膜区以IgA和C3沉积为主的系膜增生性肾小球肾炎，在我国占原发性肾小球疾病的26％～34％。临床症状复杂多变，主要表现为无症状蛋白尿、单纯镜下血尿、肉眼血尿、蛋白尿、肾病综合征、急进性新月体肾炎和急性肾功能衰竭（ARF）等。预后相差甚远，4％-20％的患者可自行缓解，每年有1％～2％的患者进入终末期肾病。     

难治性肾病综合征的治疗进展

肾病综合征是以高度浮肿、大量蛋白尿(>3.5g/24h)、高脂血症和低蛋白血症为特征的一组综合征。病理改变种类繁多,主要者有肾小球微小病变、系膜增生性肾小球肾炎、膜性肾病、膜增殖性肾小球肾炎和局灶节段性肾小球硬化等。临床治疗效果与病理类型有关,对肾上腺皮质激素(下称激素)反应最好者为肾小球微小     

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.     

Comparison of four probabilistic models (CARES(®), Calendex™, ConsExpo, and SHEDS) to estimate aggregate residential exposures to pesticides

Two deterministic models (US EPA's Office of Pesticide Programs Residential Standard Operating Procedures (OPP Residential SOPs) and Draft Protocol for Measuring Children's Non-Occupational Exposure to Pesticides by all Relevant Pathways (Draft Protocol)) and four probabilistic models (CARES(?), Calendex?, ConsExpo, and SHEDS) were used to estimate aggregate residential exposures to pesticides. The route-specific exposure estimates for young children (2-5 years) generated by each model were compared to evaluate data inputs, algorithms, and underlying assumptions. Three indoor exposure scenarios were considered: crack and crevice, fogger, and flying insect killer. Dermal exposure estimates from the OPP Residential SOPs and the Draft Protocol were 4.75 and 2.37?mg/kg/day (crack and crevice scenario) and 0.73 and 0.36?mg/kg/day (fogger), respectively. The dermal exposure estimates (99th percentile) for the crack and crevice scenario were 16.52, 12.82, 3.57, and 3.30?mg/kg/day for CARES, Calendex, SHEDS, and ConsExpo, respectively. Dermal exposure estimates for the fogger scenario from CARES and Calendex (1.50 and 1.47?mg/kg/day, respectively) were slightly higher than those from SHEDS and ConsExpo (0.74 and 0.55?mg/kg/day, respectively). The ConsExpo derived non-dietary ingestion estimates (99th percentile) under these two scenarios were higher than those from SHEDS, CARES, and Calendex. All models produced extremely low exposure estimates for the flying insect killer scenario. Using similar data inputs, the model estimates by route for these scenarios were consistent and comparable. Most of the models predicted exposures within a factor of 5 at the 50th and 99th percentiles. The differences identified are explained by activity assumptions, input distributions, and exposure algorithms.     

核因子-κB对阿霉素肾病大鼠肾小球细胞凋亡的影响

目的探讨核转录因子κB（NF-κB）对阿霉素肾病大鼠肾小球细胞凋亡的影响。方法SD雄性大鼠分成两大组，A组（假手术组）6只，B组（硬化组）6只。采用右肾切除加尾静脉注射阿霉素制成肾小球硬化动物模型。分别在8周、9周两个不同时上间点，应用免疫组化检测肾组织Caspase-3、NF—κBp65的表达，TUNEL检测肾小球细胞凋亡指数。结果在不同的时间点，B组NF-κB阳性表达指数比A组明显增高（P〈0.05）；肾小球系膜细胞（MC）凋亡指数、Caspase-3的表达与NF-κB呈正相关关系。结论NF-κB参与肾小球系膜细胞凋亡的调控，促进肾小球硬化的进程。     

The treatment of children with idiopathic nephrotic syndrome using cyclosporin]

We report our experience with cyclosporine in 14 children with steroid dependent and 7 children with steroid resistant nephrotic syndrome. Cyclosporine was started at a dose of 6 mg/kg/day and was adjusted to maintain a blood level between 60 and 100 ng/ml. 15 patients went into remission with a combined treatment of cyclosporine and prednisone; 9 of these did not have a recurrence following discontinuation of prednisone. In 7 out of these 9 patients cyclosporine was also discontinued, this led in 5 of these 7 patients to a recurrence. Seven out of 14 patients with minimal change nephropathy remained in remission following discontinuation of prednisone and in 4 others the dose of steroid required to maintain remission decreased. In only I out of 4 patients with focal segmental glomerulosclerosis was a remission obtained while in two patients with mesangial proliferation the urine remained protein free during cyclosporine treatment. In 13 patients a repeat biopsy was performed after one year or longer of cyclosporine treatment. Histopathological abnormalities related to cyclosporine were found in 9 patients. In 4 of these severe nephrotoxicity required withdrawal of cyclosporine. Treatment with cyclosporine should be restricted to steroid dependent patients with severe steroid toxicity.     

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。     

孕期服用叶酸预防和阻止小鼠腭裂的初步研究

目的:探讨叶酸对地塞米松所诱导小鼠腭裂的预防和阻止作用,为唇腭裂的预防提供新的途径。方法:选取NIH系小鼠,分为5组,第1组孕鼠在GD1-15经口灌胃0·6ml的生理盐水,第2、3、4组在GD1-15分别经口灌胃10mg/kg、30mg/kg、60mg/kg的叶酸;第5组在GD13-18经口灌胃60mg/kg的叶酸。5组孕鼠均在GD12腹腔注射50mg/kg醋酸地塞米松。在GD18断颈处死孕鼠,剖腹检查胎鼠吸收和死亡情况,对活的胎鼠检查腭裂发生情况。结果:第1组未用叶酸处理的孕鼠所产胎鼠腭裂的发生率为63·8%;第2组腭裂的发生率为64·9%;第3组腭裂的发生率为58·9%;第4组腭裂发生率为42·3%;第5组腭裂的发生率为65·3%。统计学分析第4组与第1组之间差异有显著性;第2、3、5组与第1组之间差异无统计学意义。结论:只有高剂量的叶酸(60mg/kg)才能降低胎鼠腭裂的发生率;并且要从妊娠的前期开始连续使用,才能达到良好的预防效果。     

Pro-Apoptotic and Anti-Angiogenesis Effects of Olive Leaf Extract on Spontaneous Mouse Mammary Tumor Model by Balancing Vascular Endothelial Growth Factor and Endostatin Levels

It has been proven that olive associated products such as olive leaf extract (OLE) causes significant reduction in cancer cells viability and proliferation. Female BALB/c adult mice were divided into four groups. Three days prior to oral treatments, tumors were transplanted. First group were treated with distilled water and other three groups were received, respectively, 75, 150, and 225?mg/kg/day of OLE for three weeks. For assessment of anti-angiogenesis and pro-apoptotic effect of OLE on tumor tissue, tumor volume, cell mitosis and apoptosis, and also vascular endothelial growth factor (VEGF) and endostatin levels were assessed. OLE treatment with 150 and 225?mg/kg/day lead to significant reduction in tumor volume and cell mitosis compared with the control group, while the same doses significantly increase tumor cell apoptosis. OLE treatment with 150?mg/kg/day increase endostatin levels, while the same dose did not significantly decrease VEGF levels. The VEGF level is significantly reduced by the treatment with OLE 225?mg/kg/day for three?weeks. Although, further studies are needed to clarify anti-angiogenesis and anti-apoptotic mechanism of OLE, consumption of OLE polyphenols after tumor transplantation reduced spontaneous mouse mammary tumor growth.     

丙烯腈对小鼠生精细胞Bcl-2、Bax蛋白表达的影响

目的探讨丙烯腈(AN)暴露对小鼠睾丸生精细胞Bcl-2、Bax蛋白表达水平的影响。方法将250只成年健康SPF级昆明种雄性小鼠,按体重随机分为阴性对照组、3个AN染毒组和阳性对照组,阴性对照组用生理盐水,各染毒组分别以1.25、2.50、5.00mg/kg AN腹腔注射(注射剂量为0.01ml/g BW),每天1次,连续5天,阳性对照组注射环磷酰胺40mg/kg一次。分别于首日染毒后的第7、14、21、28和35天采用颈椎脱臼法处死小鼠,采用免疫组织化学法(SABC)检测生精细胞Bcl-2和Bax蛋白的表达。结果 5个观察时间点AN 2.50mg/kg组和21天AN 1.25mg/kg组Bcl-2平均光密度值均显著低于阴性对照组(P<0.05);除21天AN 1.25mg/kg组外,所有观察时间点AN各染毒组Bax平均光密度值均显著高于阴性对照组(P<0.05)。Bcl-2在中剂量组和阳性对照组各观察时间点降低幅度均较大;Bax在各剂量组的不同时间点均以14天时升高幅度最大。结论 AN可诱导生精细胞Bcl-2蛋白表达减弱,以AN 2.50mg/kg组最为显著;同时可诱导生精细胞Bax蛋白表达增强,以14天时变化幅度较明显。     

Effects of gossypol on the estrous cycle and ovarian weight in the rat

The effect of subcutaneously injected gossypol on the estrous cycle and ovarian weights in rats was examined. Daily injections of 5 or 10 mg gossypol/kg/day for 20 days significantly reduced the ovarian weights by 32% and 29%, respectively. Injections of 0.1 and 1.0 mg gossypol/kg/day had no significant effect on ovarian weight. Similarly, ovarian weights were significantly reduced by 37% when hemi-ovariectomized animals were injected with 10 mg gossypol/kg/day for 15 days whereas those of control animals increased in weight by 15%. Animals receiving 5 or 10 mg gossypol/kg/day essentially remained in diestrus by the 15th or the 10th day of injections, respectively. No significant change was found in the liver, adrenal gland or body weight of gossypol-treated rats.     

三甲基氯化锡引起低血钾症的肾脏机制探讨

目的探讨三甲基氯化锡(trim ethyltin ch loride,TMT)引起低血钾症的肾脏机制。方法将SD大鼠随机分成3组,每组10只,分别经腹腔注射TMT 0、10.0、21.5 m g/kg,测定0.5 h、1 d、3 d、6 d和11 d血浆的钾。将大鼠随机分成2组,每组10只,分别经腹腔注射TMT 0、10.0 m g/kg,测定1 d、6 d和11 d的24 h尿量和尿钾浓度。将大鼠随机分成6组,每组10只,分别经腹腔注射TMT 0、10.0 m g/kg,测定1 d、6 d和11 d的肾小管上皮细胞膜钠钾ATP酶的活力。结果大鼠腹腔注射TMT 10.0、21.5 m g/kg后0.5 h,血钾显著下降(P<0.05),6 d和11 d血钾仍低于正常水平(P<0.05);给予TMT 10.0 m g/kg后1 d、6 d和11 d,尿量先增后减、尿排总钾均显著增加(P<0.05);1 d、6 d和11 d肾小管上皮细胞膜钠钾ATP酶活力均显著低于对照组(P<0.01)。结论TMT引起低血钾症的主要原因是肾脏排钾持续增多,其机制与TMT引起肾小管细胞膜钠钾ATP酶活力下降,进而引起K 的重吸收下降有关。