uPA和PAI-1在肺纤维化中的作用

慢性炎症和纤维化疾病都以炎性细胞和介质的聚集为特征 ,并且细胞外基质及纤溶酶系统均有明显的改变。目前发现 ,纤溶酶原激活系统的改变是肺纤维化发展中一个非常关键的环节。研究表明各种肺纤维化患者的支气管灌洗液 (BAL)中纤溶酶原活性受到的损害往往是由于尿激酶型纤溶酶原激活物 (uPA)缺失 ,以及纤溶酶原激活因子抑制物 1(PAI 1)表达增加所致。     

黄腐酸钠对糖尿病大鼠视网膜病变的作用

目的 :探讨黄腐酸钠对糖尿病大鼠视网膜病变 (DR)的治疗作用及其机制。方法 :对佐菌素诱导的糖尿病大鼠早期给予 0 .5 %黄腐酸钠 3 0mg/kg皮下注射 ,1次 /日 ,共 6个月。利用光镜和透射电镜观察其视网膜组织的形态改变 ,同时检测血浆纤溶酶原激活剂 (t PA)、纤溶酶原激活剂抑制物 (PAI 1)活性及循环血中粒细胞表面抗原CD11a、CD11b。结果 :(1)黄腐酸钠治疗组视网膜组织光镜下及超微结构变化较病变组大鼠有明显改善 ,毛细血管基底膜的增厚明显减轻 (P <0 .0 1)。 (2 )治疗组t PA、PAI 1活性的改变较病变组得以纠正 (P <0 .0 1)而接近于正常对照组水平 (P <0 .0 5 )。基底膜厚度与血浆t PA活性呈显著负相关。 (3 )治疗组CD11a、CD11b的表达受到抑制 (P <0 .0 5 )。结论 :黄腐酸钠对DR的进展有一定的抑制作用。此作用可能与维持血浆t PA、PAI 1平衡而改善纤溶活性 ,减少白细胞粘附有关。     

大鼠脑缺血后脑组织tPA和PAI-1蛋白的表达

为了探讨鼠脑缺血后脑内组织型纤溶酶原激活物 ( t PA)及其主要抑制物 - 1型 ( PAI- 1)蛋白的表达。制备了大鼠全脑和局灶性脑缺血模型 ,用免疫组化法检测 t PA和 PAI- 1蛋白的表达。结果发现 ,在全脑、局灶性脑缺血不同时间和正常鼠脑膜、脉络膜、室管膜、血管内皮等部位均有 t PA、PAI- 1免疫阳性信号 ,但小脑、海马区未见该信号。局灶性脑缺血 6 h,缺血侧中心部位的胶质细胞和梗死灶周边的缺血半影区的神经元也显示 t PA强阳性信号 ,但该细胞不表达 PA I- 1蛋白 ;缺血 18h鼠缺血侧未见t PA、PAI- 1阳性信号。本研究提示 ,脑缺血后鼠脑组织和正常脑组织均有 t PA、PA I- 1蛋白表达 ,但全脑缺血后和正常对照鼠t PA蛋白表达无明显变化 ,而局灶性脑缺血 6 h鼠缺血侧比正常侧 t PA蛋白表达增高 ,脑缺血后鼠脑组织和正常鼠 PA I- 1蛋白表达无显著变化     

siRNA-Tie1下调紧密连接相关蛋白claudin-5、occludin和ZO-1增加血肿瘤屏障通透性

目的研究Tie1 AS和Tie1表达变化对血肿瘤屏障通透性的影响和相关机制。方法建立体外血脑屏障和血肿瘤屏障模型,Real-time PCR检测h CMEC/D3细胞中Tie1 AS和Tie1的表达水平。转染p IRES2-EGFPTie1 AS表达载体上调体外血肿瘤屏障模型h CMEC/D3细胞中Tie1 AS的表达,Western blot检测Tie1的表达变化。将si RNA-Tie1转染人h CMEC/D3细胞并建立体外血肿瘤屏障模型,跨内皮电阻测量系统分析血肿瘤屏障通透性变化;Western blot和免疫荧光法检测h CMEC/D3细胞中紧密连接相关蛋白claudin-5、occludin和ZO-1的表达和分布变化。结果和正常脑微血管内皮细胞相比,体外血肿瘤屏障模型h CMEC/D3细胞中Tie1的表达显著增加,而Tie1 AS的表达显著降低。上调体外血肿瘤屏障模型内皮细胞中Tie1 AS的表达水平,能够显著降低Tie1的表达。下调体外血肿瘤屏障模型内皮细胞中Tie1的表达后屏障通透性显著下降,伴有claudin-5、occludin和ZO-1的表达下调以及在细胞膜上呈不连续分布。结论体外血肿瘤屏障模型内皮细胞中低表达的Tie1 AS能够负性调控Tie1的表达,进而通过调节紧密连接相关蛋白的表达和分布影响屏障的通透性。     

真人养脏汤对溃疡性结肠炎大鼠肠道黏膜屏障功能的保护作用

目的:观察真人养脏汤(ZRYZ)对三硝基苯磺酸(TNBS)诱导的溃疡性结肠炎(UC)大鼠肠道黏膜屏障功能的保护作用以及紧密连接相关蛋白闭锁小带蛋白1(zonula occludens-1,ZO-1)和闭锁蛋白(occludin)的表达变化,探讨其可能作用机制。方法:将Wistar雄性大鼠随机分为正常组、模型组、柳氮磺吡啶(SASP)阳性对照组、ZRYZ高剂量组和ZRYZ低剂量组。除正常组外,其它各组用TNBS/50%乙醇混合溶液局部灌肠法复制溃疡性结肠炎大鼠模型。造模成功后阳性对照组给予SASP混悬液灌胃;ZRYZ高剂量组和ZRYZ低剂量组分别按生药30.4 g/kg和15.2 g/kg剂量灌胃;正常组与模型组等量生理盐水灌胃,共21 d。给药结束后,考察大鼠疾病活动指数(DAI)变化,进行大体损伤评分,测定肠道黏膜通透性(以尿中乳果糖/甘露醇的比值表示,即L/M值),测定结肠组织髓过氧化物酶(MPO)活性,计数结肠组织杯状细胞数量,测定血清二胺氧化酶(DAO)及D-乳酸(D-LA)水平,检测ZO-1和occludin的表达。结果:与正常组相比,模型组DAI、大体损伤评分、L/M值、结肠组织MPO活性以及血清D-LA和DAO水平明显升高(P0.05),结肠组织杯状细胞数量以及ZO-1和occludin表达明显降低(P0.05);与模型组相比,ZRYZ高剂量组和ZRYZ低剂量组DAI、大体损伤评分、L/M值、结肠组织MPO活性以及血清DAO和D-LA水平明显降低(P0.05),结肠组织杯状细胞数量以及ZO-1和occludin表达明显升高(P0.05)。结论:真人养脏汤可通过降低肠道黏膜通透性,保护溃疡性结肠炎大鼠肠道上皮细胞黏膜屏障功能,其机制可能与升高ZO-1和occludin表达有关。     

慢性肾脏疾病血清和尿液纤溶活性物质的改变及临床意义

目的探讨慢性肾脏疾病血清和尿液纤溶活性物质的改变及其临床意义。方法选择38例慢性肾小球肾炎(CGN),28例肾病综合征(NS),36例非透析治疗的慢性肾功能不全(CRF)和20例正常对照作为研究对象,应用ELISA法检测血清和尿液中组织型纤溶酶原激活剂(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)的浓度,同时分析尿中t-PA和PAI-1的水平与血t-PA、PAI-1、血肌酐和24h尿蛋白总量之间相关性。结果慢性肾脏疾病出现血清t-PA、PAI-1升高,尿液t-PA、PAI-1降低,其中尿液t-PA、PAI-1的改变独立于血清,不受血肌酐和24h尿蛋白定量的影响。结论慢性肾脏疾病患者存在纤溶活性物质的异常,其中尿液纤溶活性物质的改变可反应肾脏内皮细胞损伤。     

α硫辛酸对后肢缺血再灌注损伤大鼠血神经屏障的保护作用研究

目的:研究α硫辛酸(ALA)对大鼠后肢缺血再灌注(I/R)损伤后血神经屏障的保护作用。方法:54只成年雄性SD大鼠分为3组,分别为假手术组(sham)、缺血再灌注模型组(I/R)和ALA处理组(ALA),通过手术结扎大鼠左侧髂总动脉4 h制备后肢I/R注模型,ALA处理组大鼠于术前7 d连续给予ALA。伊文思蓝(EB)渗透实验检测血神经屏障的通透性,分别于再灌注后24 h检测各组大鼠坐骨神经组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,以及丙二醛(MDA)的含量,应用Western Blot检测坐骨神经组织中紧密连接蛋白occludin和claudin-5表达变化。结果:与sham组相比,I/R组大鼠坐骨神经EB漏出增多(P 0. 05),SOD和GSH-Px活性降低(P 0. 05),MDA水平升高(P 0. 05),occludin和claudin-5蛋白表达下降(P 0. 05); ALA预处理的大鼠EB漏出减少(P 0. 05),GSH-Px和SOD活性增加(P 0. 05),MDA水平降低(P 0. 05),occludin和claudin-5蛋白表达增加(P 0. 05)。结论:ALA通过抑制机体的氧化应激水平对I/R损伤大鼠的血神经屏障起到保护作用。     

多囊卵巢综合征患者血PAI-1和uPA含量的变化

目的观察多囊卵巢综合征(PCOS)患者外周血纤溶酶原激活抑制物1(PAI-1)和尿激酶型纤溶酶原激活物(uPA)的水平。方法实验分PCOS组和对照组,PCOS组又分为肥胖组和正常体重组,用酶联免疫吸附法(ELISA)测定PCOS组与对照组患者血浆PAI-1及血清uPA水平,并测定体重指数(BMI)、腰臀比(WHR)、空腹血糖(FPG)、空腹胰岛素及胰岛素释放试验(IRT),以稳态模型公式评估胰岛素抵抗(IR),并计算胰岛素曲线下面积(AUC)。结果PCOS组与对照组相比,黄体生成素/卵泡刺激素(LH/FSH)、睾酮(T)、空腹血糖、稳态(HOMA)指数、AUC及PAI-1含量均显著升高(P<0.05)。其中,PCOS肥胖组与正常体重组相比,HOMA指数、AUC及PAI-1含量也显著升高(P<0.05)。在相关性分析中,PAI-1与HOMA指数、PAI-1与AUC、PAI-1与BMI、HOMA-IR与BMI均有显著相关性(P<0.0001)。结论胰岛素抵抗和肥胖是影响PCOS患者PAI-1水平升高的一个很重要因素,抗PAI-1的研究可能为多囊卵巢综合征的治疗提供一个新的方法。     

PAI-1在多囊卵巢综合征大鼠脂肪组织中的表达及意义

目的 探讨纤溶酶原激活物抑制因子-l(PAI-1)在多囊卵巢及正常大鼠脂肪组织中的表达及在多囊卵巢综合征(PCOS)发病中的作用.方法 应用脱氢表雄酮(DHEA)皮下注射23 d龄SD雌性大鼠20天,建立PcOS大鼠模型,应用免疫组织化学技术对PAI-1在大鼠脂肪组织的表达强度变化进行研究.结果 PCOS大鼠模型建立成功;PAI-1在PCOS组脂肪组织基质细胞上的表达明显增强.结论 PAI-1在多囊卵巢大鼠发病中起着重要作用.     

镉对大鼠血睾屏障的损伤及黄芪甲苷的保护作用

目的观察黄芪甲苷和SB203580对镉致大鼠血睾屏障破坏及相关蛋白表达改变的保护效应,探讨黄芪甲苷的保护机制。方法 21只成年雄性SD大鼠随机分为7组:单纯镉组[0.1%氯化镉腹腔内注射,1mg/(kg·d)],镉+黄芪甲苷组[镉剂量同上,同时注射黄芪甲苷,10mg/(kg·d)],镉+SB203580组[镉剂量同上,同时注射SB203580,100μg/(kg·d)],以上各组又分为连续处理5d和10d两个时间组,对照组腹腔内注射等量生理盐水。各实验和对照组动物均为3只。取睾丸做光学显微镜、电子显微镜观察以及免疫组织化学染色和Western blotting检测。结果 HE染色观察对照组支持细胞核染色较浅且不规则,镉组支持细胞内有空泡形成,镉+黄芪甲苷组与镉+SB203580组未见明显形态异常。免疫组织化学染色观察对照组闭锁小带-1蛋白(ZO-1)、紧密连接蛋白-11(claudin-11)阳性产物在生精上皮靠近基底部表达。镉组ZO-1、claudin-11阳性产物表达均显著降低(P0.05),镉+黄芪甲苷组与镉+SB203580组阳性产物表达低于对照组但明显高于镉组(P0.05)。超微结构观察对照组血睾屏障紧密连接形态完整,呈连续的电子密度较深致密线,镉组血睾屏障紧密连接及支持细胞均见不同程度破坏,镉+黄芪甲苷组与镉+SB203580组破坏程度较相应处理时间镉组为轻。Western blotting结果显示,镉组磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)水平明显增强(P0.05),镉+黄芪甲苷组与镉+SB203580组pp38MAPK水平虽高于对照组,但较镉组明显减弱(P0.05)。结论镉致大鼠血睾屏障ZO-1、claudin-11表达降低,紧密连接超微结构损伤,黄芪甲苷具有保护作用,其保护机制与抑制p38MAPK磷酸化有关。     

全反式维甲酸对大鼠脑缺血再灌注后血脑屏障通透性和ZO-1表达的影响

目的探讨全反式维甲酸(ATRA)对大鼠脑缺血再灌注后血脑屏障通透性和紧密连接蛋白ZO-1的影响。方法选取180只健康雄性大鼠,随机分为假手术组(Sham,60只),缺血再灌注组(I/R,60只)和全反式维甲酸干预组(ATRA,60只),每组又细分为1d、3d和7d三个亚组。采用Zea Longa法制作局灶性脑缺血再灌注模型,伊文思蓝渗透性实验检测血脑屏障通透性变化,免疫组织化学方法法和Western blot方法检测各组大鼠脑组织ZO-1蛋白的表达,Real-time PCR方法检测各组大鼠脑组织ZO-1mRNA的表达。结果缺血再灌注后,EB含量在1d时含量最高,3d时开始逐渐下降,而与相同时间点的I/R组相比,ATRA组EB含量显著降低(P0.01)。与Sham组相比,I/R组大鼠脑组织ZO-1蛋白及mRNA的表达水平均显著降低(P0.01),而与相同时间点的I/R组相比,ATRA组大鼠脑组织ZO-1蛋白及mRNA的表达水平均显著升高。结论全反式维甲酸降低大鼠脑缺血再灌注血脑屏障通透性可能与上调脑缺血再灌注后脑组织中ZO-1的表达相关。     

Intercellular localization of occludins and ZO-1 as a solute transport barrier of the mesothelial monolayer

A hyperpermeable state has been observed in patients on long-term peritoneal dialysis. To understand the causes of the structural or functional changes and the progression of the fibrotic process, it is important to determine which region of the peritoneum exhibits these changes. The objectives of this study were to determine the solute permeability associated with cell–cell adhesion of human peritoneal mesothelial cells (HPMCs), to study the relationship between solute permeability and localizations of tight junction-associated proteins (TJPs: occludins and ZO-1), and to assess the effect of exogenous H₂O₂ supplementation. HPMCs were cultured on a Transwell until the transmesothelial electrical resistance (TER) reached a plateau. Solute permeation tests were conducted using fluorescein isothiocyanate – labeled dextran (molecular weight: 4, 10, 70, and 150 kDa) to calculate the solute permeability coefficient (SPC). Localization of TJPs was observed by a confocal laser scanning microscope after immunofluorescent staining. TER levels increased steadily, beginning at 97.5 ± 0.7 ohms·cm² and leveling off at 128 ± 3.6 ohms·cm² (n = 4). This was accompanied by the confluence of cells and the appearance of localized TJPs. SPC levels of the HPMC monolayer on the Transwell were reduced compared to those of the Transwell itself, indicating that the HPMC monolayer provided resistance against solute permeation. Exogenous H₂O₂ supplementation revealed an increased permeability accompanied with delocalization of TJPs, particularly occludins. The delocalization of occludins and ZO-1 at the intercellular space led to a decrease in intercellular binding capacity and thus triggered an increase in the solute permeability.     

严重烫伤后脑内ZO-1mRNA表达变化与血脑屏障功能的关系

目的:探讨脑内ZO-1mRNA的表达水平在严重烫伤过程中的动态变化及其与血脑屏障功能的关系。方法:建立30%TBSAⅢ度烫伤模型,Sprague-Dawley大鼠随机分为正常对照组、烫伤组,其中烫伤组又分为烫伤后1、3、6、12、24h等5组,应用半定量逆转录-聚合酶链式反应(RT-PCR)检测ZO-1mRNA基因的表达水平,用化学法测定血脑屏障对伊文氏蓝的通透性,并分析二者的变化趋势。结果:严重烫伤后脑内ZO-1mRNA的表达迅速降低,其中以烫伤后3h降低最为显著。严重烫伤后脑组织内伊文氏蓝含量增高,其中以6h最为明显,大脑、小脑分别为(20±0.58)μg/g、(31.33±1.47)μg/g。结论:严重烫伤后的大脑内ZO-1mRNA的表达下降(P<0.01),伊文氏蓝的含量升高,ZO-1mRNA表达水平降低可能标志着血脑屏障的破坏。     

醒脑静注射液对全脑缺血再灌注大鼠血脑屏障ZO-1表达的影响

目的:探讨醒脑静(XNJ)注射液对大鼠全脑缺血再灌注后血脑屏障通透性及紧密连接蛋白1(ZO-1)表达的影响。方法:采用改良Pulsinelli四血管闭塞法建立大鼠全脑缺血再灌注模型。将雄性Wistar大鼠随机分为4组,即假手术组、全脑缺血再灌注模型组、溶剂对照组和XNJ组。每组均在缺血再灌注后24 h、48 h和72 h处理。用干湿重法测定脑组织中水含量,分光光度计法检测脑组织伊文思蓝(EB)含量,Western blot检测大脑皮层的ZO-1蛋白含量。结果:缺血再灌注后24 h,模型组、溶剂对照组和XNJ组的脑组织含水量均显著高于假手术组(P0.05),但在缺血再灌注后48 h和72 h,模型组和溶剂对照组脑组织含水量显著高于XNJ组和假手术组(P0.05)。缺血再灌注后24 h,模型组、溶剂对照组和XNJ组大鼠脑组织内EB含量均高于假手术组(P0.05),缺血再灌注后48 h和72 h,假手术组和XNJ组的EB含量显著低于模型组和溶剂对照组(P0.05)。缺血再灌注后24h,模型组、溶剂对照组和XNJ组大鼠脑皮层中的ZO-1蛋白表达水平显著低于假手术组(P0.05),同样缺血再灌注后48 h和72 h,假手术组和XNJ组皮层中ZO-1蛋白含量显著高于模型组和溶剂对照组(P0.05)。结论:在缺血再灌注后的48 h和72 h,醒脑静注射液对血脑屏障具有保护作用,可能与醒脑静注射液上调ZO-1蛋白的表达有关。     

Immunolocalization of tight junction proteins, occludin and ZO-1, and glucose transporter GLUT1 in the cells of the blood-nerve barrier

Facilitated-diffusion glucose transporter GLUT1 is abundant in the blood-nerve barrier. To observe the relationship between glucose transfer across the barrier and the molecular architecture of the barrier, we examined the localization of GLUT1 and tight junction proteins, occludin and zonula occludens-1 (ZO-1), by immunofluorescence microscopy and immunogold electron microscopy in the rat sciatic nerve. GLUT1 was enriched at the whole aspects of the plasma membranes of the cells of the barrier: perineurial cells, and endothelial cells of the blood vessels in the endoneurium. These GLUT1-positive cells were also positive for occludin and ZO-1, both of which were localized at tight junctions. ZO-1 additionally was present in the GLUT1-negative cells not serving as the blood-nerve barrier. These observations suggest that occludin in the tight junctions and GLUT1 at the plasma membranes in the cells of the barrier may constitute a mechanism for the selective transfer of glucose across the barrier while preventing the non-specific flow of blood constituents.     

Combinatorial effects of miR-20a and miR-29b on neuronal apoptosis induced by spinal cord injury

Neuronal apoptosis is one of the prominent features involved in spinal cord injury (SCI). MicroRNAs (miRNAs) are small non-coding RNAs that functions in a variety of cellular processes including apoptosis. MiRNAs have been implicated as effectors of SCI. However, role of miRNAs in SCI-associated neuronal apoptosis remains to be investigated. A number of bioinformatics approaches have suggested Mcl-1 and BH3-only family genes as potential downstream targets regulated by miR-20a and miR-29b, respectively. To determine whether miR-20a and miR-29b play a role in neuronal apoptosis of SCI by regulating those genes, we transfected Neuro-2A neuroblastoma cells with mimic and inhibitor for the two miRNAs. The miR-20a mimic decreased Mcl-1 expression and the miR-29b mimic reduced the expression of Bad, Bim, Noxa and Puma. The repressor role of miR-20a and miR-29b is confirmed by the transfection of Neuro-2A cells with their inhibitor. Moreover, miR-20a mimic or miR-29b inhibitor attenuated Neuro-2A cell viability and co-transfection of both further diminished the viability of these cells. The in vitro effects of miR-20a and miR-29b on neuronal apoptosis were corroborated by the in vivo studies. Injection of miR-20a mimic or miR-29b inhibitor into the lesion of the injured spinal cord rescued the neuronal death and co-injection of both completely abolished SCI-induced apoptosis. In conclusion, altered expression of miR-20a and miR-29b may cooperatively contribute to the neuronal cell death of SCI through down-regulating anti-apoptotic myeloid cell leukemia sequence-1 (Mcl-1) and up-regulating pro-apoptotic BH3-only proteins.     

血清miR-145、miR-29联合miR-217检测在膀胱癌的表达差异及价值分析

目的探讨血清微小RNA-145(microRNA-145,miR-145)、miR-29与miR-217检测在膀胱癌中的临床价值。方法选取2016年2月至2018年5月在我院经穿刺或术中病理切片确诊的膀胱癌患者80例,同期收取80例膀胱炎患者和80例健康体检者。应用实时荧光定量PCR(quantitative real-timePCR,RT-PCR)仪对血清miR-145、miR-29与miR-217的相对表达量进行检测。结果膀胱癌患者血清miR-145、miR-29和miR-217表达水平(检测结果经负对数转换后呈正态分布)显著低于膀胱炎患者和健康对照者(P<0.05),而膀胱炎患者和健康对照者间血清miR-145、miR-29和miR-217水平差异均无统计学意义(P>0.05)。血清miR-145、miR-29与miR-217表达水平与膀胱癌淋巴结转移及TNM分级呈线性关联(P<0.05)。ROC曲线分析显示,血清miR-145、miR-29和miR-217在区分膀胱癌与膀胱炎患者和健康对照的灵敏度/特异性分别为81.3%/82.9%、82.7%/89.7%和77.2%/83.3%;而联合三者后在区分膀胱癌与膀胱炎患者和健康对照的灵敏度显著提高,达到91.7%。二元Logistic回归分析显示,在校正了年龄、性别、BMI、吸烟、饮酒后,血清低miR-145、低miR-29和低miR-217是膀胱癌的独立危险因素。结论血清低miR-145、低miR-29和低miR-217水平对膀胱癌的诊断以及在评估膀胱癌患者发生肿瘤远处转移中均具有重要的临床意义。     

Impact of cyclosporin on podocyte ZO-1 expression in puromycin aminonucleoside nephrosis rats

Puromycin aminonucleoside (PAN)-induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. To investigate whether proteinuria in the PAN model is associated with an alteration of zonula occludens-1 (ZO-1) expression within the glomeruli, and whether cyclosporin A (CsA) has an effect on proteinuria and ZO-1 expression in this model, eighteen Sprague Dawley (SD) rats were assigned into three groups. Twelve rats received a single intraperitoneal injection of PAN (15 mg/100 g). The other six rats received an equal volume of saline (normal control group; control). CsA solution was administered intraperitoneally once a day for 20 days after the PAN injection (n=6, PAN+CsA). The remaining six rats received PAN, but they didn't receive CsA (n=6, PAN). Compared to control rats (35.1+/-5.4 mg/day), the 24-hour urinary protein excretion on day 18 was significantly higher in the PAN rats (1021.9+/-128.9 mg/day, p<0.01), and the CsA treatment partly reversed the increase in proteinuria in the PAN rats (556.4+/-102.3 mg/day, p<0.05). Glomerular ZO-1 protein expressions were significantly increased in the PAN rats as compared to the control group on day 20 (176%, p<0.01). CsA treatment for 20 days in the PAN rats inhibited the increase in ZO-1 protein expression by 71.1% (p<0.05). CsA treatment significantly diminished the glomerular ZO-1 expression in the PAN rats as assessed by immunohistochemistry. CsA treatment significantly reduced proteinuria and the diminished glomerular ZO-1 expression in a PAN nephrosis rat model. These findings suggest the potential role of the slit diaphragm associated proteins in the development of the nephrotic syndrome, and CsA decreased the proteinuria probably by a direct action on the expression of these proteins in podocytes. Further investigations are needed to clarify the role of slit diaphragm associated proteins in the development of PAN nephrosis.