目的:观察泼尼松对阿霉素肾病大鼠粘着斑激酶(Focal Adhesion Kinase,FAK)、核因子-κB受体活化因子(Receptor Activator of Nuclear Factor Kappa B,RANK)、核因子-κB受体活化因子配体(Receptor Activator of Nuclear Factor Kappa B Ligand,RANKL)、p38丝裂原活化蛋白激酶(p38 Mitogen-activated Protein Kinase,p38MAPK)、核转录因子-κB(Nuclear Factor-κB,NF-κB)表达的影响.方法:利用随机数字表法把SD大鼠分为正常组(尾静脉一次性注射等量生理盐水)、模型组(注射盐酸阿霉素6.5 mg/kg造模)、治疗组(成功造模后以泼尼松每天10 mg/kg灌胃),在实验不同的时间点测定24 h尿蛋白定量,观察肾组织电镜结果,用电泳迁移率变动分析(Electrophoretic Mobility Shift Assay,EMSA)检测NF-κB含量,用实时荧光定量聚合酶链式反应(Quantitative Real-time Fluorescence Polymerase Chain Reaction,qRT-PCR)检测FAK、p38MAPK、RANK、RANKL、Nephrin表达水平的变化,用Western blot检测肾组织FAK、RANK、RANKL、Nephrin蛋白以及p38MAPK蛋白和磷酸化蛋白.结果:①与正常组相比,模型组尿蛋白水平升高(P<0.01);用药后的治疗组尿蛋白水平下降(P<0.01);②模型组电镜下可见足细胞足突广泛融合、肿胀或增宽,治疗组明显减轻;③模型组PCR结果示FAK、p38MAPK、RANKL、RANK mRNA表达较正常组升高(P<0.01),治疗组FAK、p38MAPK、RANKL、RANK mRNA表达较模型组降低(P<0.01);④与正常组相比,模型组RANK、RANKL蛋白以及FAK、p38MAPK总蛋白和磷酸化表达升高(P<0.01),Nephrin蛋白表达减少(P<0.01);与模型组相比,治疗组RANK、RANKL蛋白以及FAK、p38MAPK总蛋白和磷酸化表达降低(P<0.05),Nephrin蛋白表达升高(P<0.05);⑤EMSA检测结果显示,与正常组相比,模型组NF-κB表达增多(P<0.01);与模型组相比,治疗组NF-κB表达水平降低(P<0.01).结论:阿霉素肾病肾组织中有RANK/RANKL的表达,经激素治疗,FAK-p38MAPK/RANKL-RANK-p38MAPK的通路被抑制,使NF-κB入核减少,炎症反应被控制,蛋白尿减少.

研究发现益肾降浊冲剂对延缓慢性肾衰竭肾功能的进展、降低蛋白尿及改善临床症状等方面有良好疗效[1],该方中黄芪、太子参、茯苓、白术健脾益气,能够增强机体免疫机能,促进机体对铁的吸收、促进骨髓造血进而改善贫血[2].慢性肾脏病(CKD)患者随着肾功能衰竭进展,铁调素表达增加,外周血清铁含量下降.铁缺乏可增强弗林(furin)蛋白酶活性,使全段纤维细胞生长因子(IFGF23)裂解为C末端成纤维细胞生长因子(CFGF23)增多,抑制IFGF23的降磷作用[3].

目的 从"浊毒理论"探讨加味四君子汤对肾病综合征的治疗.方法 40只SPF级大鼠以随机数字表法分为正常组8只、造模组32只.造模组大鼠造模成功后再次随机分为模型组8只、激素组8只、中药组8只、联合组8只.正常组和模型组大鼠以生理盐水灌胃,剂量为20 ml/(kg·d),激素组大鼠以泼尼松灌胃,剂量为10 mg/(kg·d);中药组大鼠以中药灌胃,剂量为20 ml/(kg·d);联合组以中药和泼尼松联合灌胃,剂量分别为20 ml/(kg·d)和10mg/(kg·d).在灌胃第14天、第28天取血备用.用双缩脲比色法测定各组大鼠24 h尿总蛋白定量;电子显微镜下观察各组大鼠肾脏的病理改变.结果 与模型组比较,灌胃第14天、第28天激素组、中药组、联合组24 h尿蛋白均降低(P<0.05).灌胃28 d与灌胃14 d比较,模型组24 h尿蛋白升高,激素组、中药组、联合组均降低(P<0.05).模型组大鼠肾脏组织电镜下表现为足突增宽、足突部分融合或弥漫性融合,足细胞肿胀;而激素组、中药组、联合组电镜下肾小球的病变明显减轻,只见足突部分融合.结论 加味四君子汤可有效减少蛋白尿,减轻肾小球病变.

目的:探讨加味四君子汤对泼尼松干预的阿霉素肾病大鼠胫骨细胞中核因子(Nuclear Factor,NF)-κB通路的影响.方法:通过尾静脉注射盐酸阿霉素造模,将40只阿霉素肾病大鼠模型按照分层随机法分为5组:正常组(N组)、模型组(M组,予阿霉素溶液注射尾静脉)、激素组(A组,予泼尼松)、中药组(B组,予中药)、中药加激素组(C组,予中药加泼尼松),连续灌胃14d.尿液标本在注射阿霉素造模后的第7、14天后采集.光镜下观察胫骨组织学形态.采用实时荧光定量聚合酶链式反应(Polymerase Chain Reaction,PCR)、蛋白质印迹(Western Blotting)法检测核因子-κB受体活化因子配体(Receptor Activator of NF-κB Ligand,RANKL),核因子-κB受体活化因子(Receptor Activator of NF-κB,RANK)和p38丝裂原活化蛋白激酶(p38 Mitogen-activated Protein Kinase,p38 MAPK)的mRNA和蛋白在胫骨细胞中的表达情况.用凝胶电泳迁移分析法(Electrophoreticmobility Shift Assays,EMSA)检测NF-κB浓度.结果:与N组相比,M组第7、14天尿蛋白升高;各治疗组与M组相比尿蛋白均下降(P<0.01).光镜下A组骨小梁排列相对紊乱,B、C组骨组织形态得到改善.与N组相比,M组RANKL、RANK、p38 MAPK的mRNA及蛋白水平均升高,NF-κB表达增多.与M组相比,A组均升高,B、C组均降低;与A组相比,B、C两组均降低(P<0.01).结论:加味四君子汤在减轻尿蛋白的同时,可以通过抑制骨组织RANK-RANKL-p38 MAPK-NF-κB通路抑制破骨细胞分化.

目的 探讨耳穴贴压法对血液透析患者营养不良的临床疗效.方法 选择维持性血液透析患者120例,采用随机数字表法分为对照组和治疗组各60例.对照组给予常规治疗及血液透析,治疗组在常规治疗及血液透析基础上进行耳穴贴压疗法.治疗2个月后,采用综合性营养评估法(GNA)评价两组患者的营养状况.结果 治疗后,治疗组的营养不良发生率降低,且无重度营养不良发生,但与对照组比较差异无统计学意义(P>0.05);治疗组血清白蛋白显著提高,消化道症状评分及GNA评分明显下降,与对照组比较差异均有统计学意义(均P<0.05).结论 耳穴贴压疗法辅助治疗能改善维持性血液透析患者的营养不良状态,提高患者生活质量,值得临床应用.

目的 探讨加味四君子汤在抑制阿霉素肾病大鼠RANK/RANKL信号通路及减少蛋白尿的作用机制.方法 将40只SPF级雄性大鼠,按随机数字表法分为正常组8只和造模组32只,造模组大鼠经尾静脉一次性注射盐酸阿霉素6.5 mg kg,7 d后判定造模成功后随机分为模型组、激素组、中药组、联合组各8只.正常组和模型组大鼠每日以生理盐水20 mL/(kg·d)灌胃,激素组以泼尼松10 mg/(kg·d)灌胃,中药组以加味四君子汤20 mL/(kg·d)灌胃,联合组以加味四君子汤20 mL/(kg·d)和泼尼松10 mg/(kg·d)灌胃,每日1次,连续灌胃28 d.在灌胃第7天、第14天、第28天采用双缩脲比色法测定24 h尿蛋白定量;在灌胃结束处死大鼠,取出肾皮质组织,于电镜下观察肾组织病理形态学改变;取出肾组织,采用实时荧光定量检测FAK、P38、RANK、RANKL、Nephrin mRNA表达水平,Western blot检测FAK、P38、p-FAK、p-P38、RANK、RANKL、Nephrin蛋白相对表达水平,EMSA法检测NF-κB.结果 ①24 h尿蛋白定量:模型组比正常组明显升高(P<0.01);各用药组比模型组均降低(P<0.05);灌胃第28天与灌胃第14天比较,模型组升高,各用药组均降低(P<0.05).② 病理形态学:模型组肾组织足细胞肿胀,足突增宽,部分或弥漫性融合;各用药组肾小球病变较模型组明显减轻,仅见足突部分融合.③ 灌胃第14天、第28天,与正常组比较,模型组FAK、p-FAK、P38、p-P38、RANK、RANKL mRNA和蛋白相对表达水平显著升高,Nephrin mRNA和蛋白相对表达水平降低(P均<0.01);与模型组比较,各用药组FAK、p-FAK、P38、p-P38、RANK、RANKL mRNA和蛋白相对表达水平均降低,Nephrin mRNA和蛋白相对表达水平均升高(P均<0.05).④ 灌胃第14天、第28天,与激素组比较,中药组NF-κB增多(P<0.05),联合组减少(P<0.01).结论 肾组织有RANK、RANKL存在,阿霉素可诱导其激活从而导致肾损害.加味四君子汤可抑制阿霉素肾病肾组织FAK、p-FAK、P38、p-P38、RANK、RANKL的表达,但对控制NF-κB入核弱于激素,降蛋白尿作用弱于激素.

慢性肾脏病(CKD)是多种原因导致的慢性肾功能衰退性疾病,随着肾小球损伤的不断加重,病情的发展逐步走向终末期肾脏病(ESRD),这个过程中会逐渐出现各种不同程度的并发症,包括血管钙化、钙磷代谢紊乱、贫血等,这些并发症会严重影响患者的生活质量和生存时间.成纤维生长因子(FGF23)在慢性肾脏病中的研究是近几年来的热点,会随着CKD肾小球滤过率的降低而逐渐升高,且其在钙磷代谢、骨代谢、贫血等方面发挥重要调节作用,甚至可反映早期肾功能变化情况.因此本文就FGF23及其相关作用与CKD并发症的联系作一综述.

目的:研究Klotho在慢性肾脏病(Chronic Kidney Disease,CKD)患者血清中的变化,探讨其作为CKD早期肾损伤生物标记的意义.方法:回顾收集2013年9月-2014年12月于福建省人民医院就诊的CKD非透析患者130例.分析CKD不同分期患者血清Klotho水平,研究其与全段甲状旁腺激素(iPTH)、成纤维细胞生长因子(FGF23)以及血钙、血磷的相关性.结果:CKD2-5期与CKD1期患者相比,血清Klotho水平降低,且随着CKD的进展,血清Klotho水平逐渐降低(P<0.05);CKD2-5期与CKD1期患者相比,血清FGF23水平升高(P<0.05);且随着CKD的进展,血清FGF23水平逐渐升高(P<0.05);与CKD1期比,CKD3-5期血钙均降低(P<0.05),但各组间血钙水平差异无统计学意义(P>0.05);与CKD1期比,CKD4-5期血磷及钙磷乘积均升高(P<0.05);与CKD3期比,CKD4-5期血磷及钙磷乘积均升高(P<0.05),但两组间血磷及钙磷乘积水平差异无统计学意义(P>0.05);相关分析显示:Klotho与年龄(r=-0.575,P<0.001)、血磷(r=-0.406,P<0.001)、钙磷乘积(r=-0.367,P<0.001)、血清肌酐(r=-0.567,P<0.001)、FGF23(r=-0.616,P<0.001)、iPTH(r=-0.551,P<0.001)呈负相关,与血钙(r=0.242,P=0.005)、表皮生长因子受体(eGFR)(r=0.779,P<0.001)呈正相关;多元逐步线性回归分析显示,eGFR、年龄是血清Klotho水平的主要影响因素.结论:CKD疾病早期患者血清Klotho就开始变化,参与CKD患者iPTH、FGF23以及血钙、血磷水平的调节,因此,Klotho可作为CKD早期肾损伤生物标记物,早期干预血清Klotho的平衡,可能对纠正矿物质代谢紊乱具有一定的意义.

目的:探讨加味补阳还五汤(MDIY)对七氟烷麻醉处理后的早期糖尿病肾病(DN)大鼠肾足细胞的影响.方法:将早期DN大鼠随机分为4组(每组n=16):MDIY组(A组),罗格列酮组(B组),MDIY+罗格列酮组(C组)和模型对照组(D组),另设正常大鼠(E组)为空白对照组.连续治疗7周,每天收集大鼠死亡数和葡萄糖(GLU)、肌酐(CR)、尿素氮(BUN)和尿微量白蛋白(UAL).七氟烷麻醉处理后采集标本,通过苏木精和伊红染色(H&E)收集肾脏和肾病理变化检查.应用实RT-PCR和western blotting检测评估肾足突细胞各m-RNA的表达水平,包括nephrin、podocin、α-SMA和desmin的表达.结果:在治疗周期中,A组、B组和C组的GLU和UAL水平均低于D组(P＜0.01),且7周后3组的GLU、CR和BUN水平也都远低于D组(P＜0.05).其中,C组的上述生化指标远低于A组和B组(P＜0.05).相比于正常SD大鼠,通过H&E染色,观察各组的肾小球疾病、慢性肾小管间质损伤和肾小球足细胞损伤的发病率.然而,只有C组显示更能优化改善上述损伤的发病率.在A组、B组和C组与D组比较,α-SMA和desmin的表达减少,而nephrin和podocin的表达明显增加(P＜0.05);C组不仅nephrin和podocin mRNA 表达(P＜0.05),而且在蛋白表达方面均观察有协同效应.结论:MDIY对早期DN引起的肾功能损害是一种保护作用,可以大大提高与罗格列酮相结合的治疗效果,其机制是通过增加nephrin、podocin的表达和减少α-SMA、desmin的表达,从而推测MDIY具有显著的协同治疗DN作用.七氟烷预处理能改善糖尿病肾病足细胞结构和功能,对围术期外科快速康复有利.

目的 探讨益肾降浊冲剂对脾肾气虚夹湿浊型慢性肾脏病(CKD) 3～5期患者治疗前后血清IFGF23、CFGF23及血磷的变化及对临床治疗的指导意义. 方法 随机选择76例2015年9月-2017年12月在我院肾内科住院及门诊治疗的CKD 3～5期患者,均为脾肾气虚夹湿浊证,其中CKD 3期37例,CKD 4期30例,CKD 5期9例.另选取同期在本院体检的健康志愿者30例作为对照组.治疗组在常规西医治疗基础上加服益肾降浊冲剂,疗程4周,对照组无需治疗.应用双抗体夹心酶联免疫吸附(ELISA)方法检测血清IFGF23、CFGF23,BECKMAN-C800全自动生化分析仪测定血磷(P)、尿素氮(BUN)、血肌酐(Scr),根据简化MDRD公式计算内生肌酐清除率(Ccr). 结果 ①与对照组比较,治疗组治疗前后IFGF23、CFGF23均明显升高(P均＜0.05);CKD3～5期同期治疗前后比较,IFGF23、CFGF23水平无明显变化(P＞0.05);IFGF23、CFGF23均随着肾功能下降而逐渐升高(P＜0.05).②CKD 3～5期治疗后Scr、BUN、P水平较治疗前下降(P＜0.05),Ccr较治疗前升高(P＜0.05). 结论 益肾降浊冲剂短期内不能改善CKD 3～5期患者血清IFGF23及CFGF23水平,但可以改善其肾功能,降低P水平.

目的 基于Pyk2通路探讨加味四君子汤对阿霉素肾病大鼠的作用. 方法 将实验用SD大鼠30只采用随机数字表法分为正常组、模型组及中药组,诱导阿霉素肾病大鼠模型.中药组在阿霉素注射后第7天予中药灌胃,正常组和模型组予等量生理盐水灌胃.实验的第7、21、35天分别检测各组24 h尿蛋白定量及电镜下观察大鼠肾组织;检测各组肾组织中Nephrin、Nephrin mRNA、Pyk2 mRNA、Pyk2、Pyk2磷酸化蛋白水平(pPyk2)及pPyk2/Pyk2比值. 结果 ①24 h尿蛋白定量:模型组较正常组明显升高(P＜0.01),中药组较模型组降低(P＜0.05).②Nephrin及Nephrin mRNA水平:第21、35天,模型组较正常组均明显减少(P＜0.01),中药组较模型组增高(P＜0.05).③Pyk2 mRNA水平:第21、35天,模型组和中药组比正常组均升高(P＜0.05),但第35天,中药组比模型组明显减少(P＜0.01).④pPyk2、pPyk2/Pyk2比值:第21、35天,模型组较正常组均有上升(P＜0.05和＜0.01),而中药组比模型组均有降低(P＜0.01). 结论 阿霉素可通过损伤足细胞,抑制Nephrin蛋白,激活Pyk2蛋白磷酸化引起肾病综合症的发生;加味四君子汤可抑制阿霉素肾病大鼠肾组织中Pyk2激活,上调Nephrin蛋白水平,改善肾组织足突病变,减少尿蛋白,进而保护肾小球的滤过屏障作用.

我们通过观察尿毒症患者血液透析前后湿浊证和脾肾气虚的变化,研究透析对改善脾肾气虚夹湿浊证尿毒症患者的湿浊与脾肾气虚中医证候积分的影响,探讨血透后尿毒症患者的中医证候转归. 1 临床资料 1.1 诊断标准 1.1.1 中医诊断标准参照《中药新药临床研究指导原则》中脾肾气虚证、湿浊证诊断标准[1].脾肾气虚证:主症:畏寒肢冷,倦怠乏力,少气懒言,食少纳呆,腰酸膝软;次症:脘腹胀满,腰背部冷痛,大便不实,小便清长,舌质淡胖有齿印,脉沉弱.湿浊证:主症:恶心,呕吐,肢体困重乏力,食少纳呆;次症:脘腹胀满,口中黏腻不适,舌苔厚腻.诊断需具备主症2项或主症1项、次症2项即可.辨证时至少有2名中级职称以上的中医师认定.

血清铁调素通过下调血清铁水平,对维持体内铁稳态起到重要的调节作用,益肾降浊冲剂为福建中医药大学附属人民医院制剂,长期应用于临床,疗效甚佳.本研究通过观察血清矿物质、铁调素水平的变化,探讨益肾降浊冲剂对慢性肾脏病(chronic kidney disease,CKD) 3～5期患者改善矿物质代谢紊乱、纠正肾性贫血的作用.

益肾降浊冲剂为我院制剂,长期应用于临床,本研究通过测定慢性肾脏病(chronic kidney disease,CKD)3～5期患者使用益肾降浊冲剂前后血钙、血磷、成纤维细胞生长因子23 (fibroblast growth factor 23,FGF23)水平的变化,对于指导益肾降浊冲剂对CKD3～5期患者的治疗有重要意义.

Objective:To explore the influence of Niaoduqing(NDQ) Particle on the calcium,phosphorus and fibroblast growth factor 23(FGF23) in patients with CKD stage 3-5.Method:According to the standard of NKF-K/DOQI proposed,fifty-four CKD patients were randomly divided into the treatment group(Niaoduqing Particle) and the control group,at the same time,20 cases were selected as the normal group.FGF23,iPTH,BUN,Scr,Ca,P levels and Ucr were determined,then GFR was calculated based on MDRD equation.Result:Compared with normal group,with the decline of GFR,the level of P, FGF23,BUN,Scr in the serum of the patients with CKD stage 3-5 were significantly increased,the level of Ca was significantly decreased,the differences were statistically significant(P<0.01).CKD stage 3-4:compared with the pretherapy,serum P, FGF23,Scr level were decreased(P<0.01 orP<0.05),GFR was increased(P<0.01) in the treatment group,there was no significant difference in BUN(P>0.05).In the control group,FGF23 level was decreased(P<0.05),Scr decreased and GFR increased,but there were no statistically significant differences(P>0.05).Ca of the two groups were increased,but there had no statistical significances(P>0.05).Compared with the control group,the P and FGF23 level of the treatment group were decreased significantly(P<0.05 orP<0.01).CKD stage 5:compared with the pretherapy,GFR and Ca of the treatment group were significantly increased(P<0.01 orP<0.05),FGF23 of the two groups were decreased(P<0.05 orP<0.01),BUN,Scr, P decreased,but there were no statistically significant differences(P>0.05).GFR of the control group was decreased,but there had no statistical significances(P>0.05).Conclusion:Niaoduqing Particle can improve the levels of calcium,phosphorus and FGF23 of the patients,and it may play an important role to delay the progression of CKD-MBD by improving the calcium and phosphorus metabolism,reducing the expression of PTH,FGF23 and other factors.

Objective: To observed the effects of Modified Sijunzitang combined bone marrow mesenchymal stem cells(BMSCs) on the bone metabolism of adriamycin-induced nephritic rats. Methods: Generate adriamycin-induced nephriticrats(n=60), and randomly divide them into six groups as group A:the normal group, group B: the model group, group C: the hormone group, group D: nephritic rats with stem cells transplant, group E: nephritic rats with stem cells transplant+ hormone treatment, group F: nephritic rats with stem cells transplant+TCM treatment.The urine samples were collected on the on the day 7, 21 and 35 respectively after adriamycin injection,and urine protein levels were measured by automatic biochemistry analyzer.The serum protein levels of osteoprotegerin(OPG), nuclear factor-κB receptor activating factor ligand(RANKL) were detected by ELISA. Using real-time quantitative PCR to measure the expression of OPG, RANKL and FAK in tibia tissue.Using Western blot to measure the protein expression of FAK in tibia tissue. Results: compared to the group A, on the day7, urinary protein level of group B to E all showed significant increase; compared to group B, day 21 and 35 day, the urinary protein of the C,D,E and F decreased. in the group C, the serum of OPG, OPG m RNA and FAK m RNA with its protein decreased, the serum of RANKL、RANKL m RNA increased Compared to the B group; in both group D and F, the serum of OPG、OPG m RNA and FAK m RNA with its protein increased, the serum of RANKL, RANKL m RNA level were reduced as compared to the C group; Compared with the D group, E group showed decreased level of the OPG serum、m RNA with FAK m RNA, protein, and increased level of the RANKL serum and m RNA. Conclusion:FAKOPG/RANKL pathway may play an important role in the formation of prednisone-induced osteoporosis, whereas Modified Sijunzitang combined BMSCs could slow the prednisone-induced bone osteoporosis formation through reverse this trend to some extent, which can provide synergistic effects.

目的:探讨加味四君子汤对阿霉素肾病大鼠的治疗作用及对FAK/p38途径的影响.方法:建立阿霉素肾病综合征大鼠模型,以随机数字表随机分为正常组、模型组、激素组、中药组(加味四君子汤)、中药+激素组,每组10只.测大鼠24h尿蛋白;电镜下进行肾脏超微病理观察,实时荧光定量PCR检测肾组织FAK、p38mRNA表达,Western Blot检测肾皮质FAK、p38蛋白及磷酸化.结果:①第21天,激素组、中药组、中药+激素组尿蛋白均较模型组降低(P＜0.05,P＜0.01).第35天,与模型组比较,3组尿蛋白均显著性降低(P＜0.01).第35天与第21天相比,模型组显著性升高、激素组和中药+激素组显著性降低(P＜0.05).②模型组足细胞肿胀,足突增宽、部分或弥漫性融合;各治疗组肾小球病变明显减轻,仅见部分足突融合.③与模型组比较,各药物干预组FAK mRNA、p38 mRNA表达显著性减少(P＜0.01).④模型组FAK总蛋白及FAK、p38磷酸化蛋白显著性增高(P＜0.01),与模型组比,各药物干预组FAK总蛋白及FAK、p38磷酸化蛋白显著性降低(P＜0.05).结论:阿霉素可通过FAK/p38途径导致阿霉素肾病的形成;肾组织FAK磷酸化,可诱导下游p38通路激活,介导肾脏损伤;加味四君子汤、激素能抑制FAK/p38通路,降低阿霉素肾病大鼠蛋白尿.

OBJECTIVE:To investigate the effects of prednisone on the expressions of FAK and Pyk2 in the kidneys of rats with adriamycin-induced nephritis.METHODS:Thirty SD rats were randomized into normal control group, adriamycin-induced nephritic model group, and prednisone treatment group (n=10). Prednisone was administered at 10 mg/kg once daily in nephritic rats starting since the 7th day after adriamycin injection. Twenty-four-hour proteinuria was measured in the rats at different time points, and renal tissue histology was examined using transmission electron microscope. The expression levels of Pyk2, FAK and nephrin mRNA in the renal tissue were detected tested by RT-PCR, and the protein expressions of FAK, Pyk2, phosphorylated Pyk2 and phosphorylated FAK-Tyr397 were detected by Western blotting; immunohistochemistry was used for detecting nephrin protein expression in the kidney.RESULTS:Compared with the normal control group, the rats with adriamycin-induced nephritis showed significantly increased proteinuria (P<0.01), which was obviously lowered by prednisone treatment (P<0.01). Transmission electron microscopy revealed extensive fusion of the foot processes of the podocytes in the model group. Prednisone treatment promoted nephrin expression in the kidney (P<0.05). Compared with the control group, the model and prednisone treated groups showed significantly lowered nephrin mRNA expression (P<0.01) but increased FAK mRNA expression (P<0.01), but prednisone-treated group had a higher nephrin mRNA expression than the model group (P<0.05). The model group exhibited significantly increased expressions of FAK total and phosphorylated proteins, P-FAK/FAK, and P-Pyk2/Pyk2 (P<0.01), which were all lowered in the treatment group (P<0.01). Correlation analysis suggested that the expressions of FAK mRNA, FAK, pFAK, Pyk2 mRNA and pPyk2/Pyk2 were positively correlated with proteinuria (r=0.819, 0.750, 0.838, 0.762, 0.934, respectively, P<0.01).CONCLUSIONS:Adriamycin increases phosphorylated FAK and Pyk2 expressions to mediate kidney injury in rats. Prednisone inhibits Pyk2 and FAK activation, decreases proteinuria, and alleviates podocyte lesions to protect the glomerular filtration barrier.

Objective To investigate the change of IL-17 pre-hemodialysis and post-hemodialysis,and relationship between IL-17and hemodialysis,to find the differentiation direction of CD4+T cells post-hemodialysis.Methods Twenty five CRF patients undergoing hemodialysis treatment more than 1/2 year were chosen in observation group,and 30healthy volunteers were chosen in control group.IL-17,BUN,phosphorus(P)changes were observe in pre-hemodialysis and post-hemodialysis.Results BUN,P,and IL-17 levels of observation group in pre-hemodialysis were significantly higher than those of control group(P0.05),IL-17levels of observation group in pre-hemodialysis were significantly higher than those of observation group in post-hemodialysis(P0.05).BUN,and P levels in pre-hemodialysis were significantly lower than those of observation group in post-hemodialysis(P0.01).Conclusion It suggests that IL-17 may involve in the abnormality of immunity and the pathology of microinflammation in MHD patients after hemodialysis.Uremic symptoms leads to high expression of IL-17.It may suggests that the main differentiation direction of CD4+T cells in post-hemodialysis is IL-17.

Objective To investigate the repair effects of bone marrow mesenchymal stem cells (BMSCs) on adriamycin-induced nephritic rats and effects on FAK. Methods The rats models were induced by adriamycin to cause nephritic syndrome. Then, the rats were divided into four groups. The first group was the model without any treatment. The second group were treated with BMSCs. The third group were treated with prednisone. And the forth group were treated with BMSCs and prednisone. The quantitation of proteinuria was tested respectively. Histology of kidney was tested by transmission electron microscope. The expression levels of Nephrin, podocin and Desmin mRNA were tested by RT-PCR. The Nephrin protein levels were tested by immunohistochemistry. The expression level of FAK and phosphorylated FAK-Tyr397 were detected by western blot. Results (1) Compared with normal group, rats in model group developed massive Proteinuria with foot process fusion, while in BMSCs group were significantly ameliorated. (2)Nephrin mRNA expression in model group were lower than normal after adriamycin injection (P<0.05), while Desmin and FAK mRNA expression in model group were higher than normal group (P<0.05);Nephrin mRNA expression in treatment groups were lower than model group 5 weeks after adriamycin injection (P<0.05), while Desmin and FAK mRNA expression in treatment groups were lower than model group (P<0.05). (3)Nephrin protein expression in model group and the treatment groups were lower than normal group (P<0.05);Nephrin expression in treatment groups were higher than model group three weeks after adriamycin injection (P<0.05). (4)FAK total protein and phosphorylated proteins in model group higher&nbsp;than normal group (P<0.01). The protein level of treatment groups lower than model group (P<0.05). Conclusion Prednisone and BMSCs play a protective effect in ardriamycin-induced nephrotic rats via the inhibition of FAK and by altering the expression and distribution of Nephrin and moderating the expression of Desmin. BMSCs play a protective effect in ardriamycin-induced nephrotic rats.