CD34在IgA肾病肾小管间质病变中的表达及意义

目的:研究白细胞分化抗原CD34在IgA肾病肾小管间质病变中的表达变化,探讨其在IgA肾病进展过程中的作用.方法:应用免疫组织化学双标记技术检测不同小管间质病变程度的IgA肾病患者肾组织内CD34和α-平滑肌激动蛋白(α-SMA)的表达.肾小管间质病变分级采用Katafuchi积分.详细收集每例患者肾活检时的24 h尿蛋白定量(TUPr)及内生肌酐清除率(Ccr),并与免疫病理结果进行相关分析.结果:无小管间质病变组未见CD34的表达,α-SMA仅表达于间质的动脉壁;轻度小管间质病变组CD34和α-SMA表达散在,主要见于小管间质受损部位;中、重度病变组较轻度病变组CD34和α-SMA的表达显著增加(P＜0.05);小管间质内CD34的表达与α-SMA的表达及TUPr、Ccr具有显著相关性(P＜0.05).结论:随小管间质病变进展而出现的CD34表达增多可能在IgA肾病中发挥重要作用.     

Wnt/β-catenin在IgA肾病中的表达及意义

目的:探讨Wnt/β-catenin及其下游靶基因在IgA肾病中的表达,分析其与患者的临床病理参数的相关性。方法:根据肾小管间质病变程度分组,采用RT-PCR、Western blot和En Vision-免疫组化技术检测各组IgA肾病患者以及正常对照组患者肾活检组织中Wnt/β-catenin及其下游靶基因snail、基质金属蛋白酶-7(MMP-7)、α-平滑肌动蛋白(α-SMA)的表达,各组之间进行比较。结果:IgA肾病患者肾活检组织中β-catenin、snail、MMP-7、α-SMA mRNA和蛋白表达水平较正常对照组升高(P0.05)。β-catenin、snail在伴有轻度肾小管间质病变的IgA肾病患者肾活检组织中表达水平高于无肾小管间质病变的IgA肾病患者(P0.05),其后随着肾小管间质病变程度的加重逐渐下降。MMP-7、α-SMA在IgA肾病患者肾活检组织中的表达水平与肾小管间质病变的严重程度相一致。结论:Wnt/β-catenin及其下游靶基因在IgA肾病中表达异常,可能参与IgA肾病的发生发展。     

血、尿NGAL与IgA肾病临床与病理的相关性研究

目的:探讨血、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平与IgA肾病(IgAN)患者临床与病理表现的关系。方法:选择初次诊治经肾活检病理检查确诊为IgAN且未经激素或免疫抑制剂治疗的患者40例,同时选择10例健康体检者作为对照。收集临床和病理资料,应用酶联免疫吸附法(ELISA)检测血、尿NGAL水平,并分别用IgAN牛津分型和Katafuchi半定量标准对病理进行评分。分析血、尿NGAL与IgAN患者临床及病理指标的相关性。结果:血、尿NGAL反映IgAN肾功能情况较血肌酐(Scr)、血尿素氮(BUN)更敏感,与高血压、Scr、BUN、牛津分型的系膜增殖积分(M)、间质纤维化或小管萎缩(T)以及Katafuchi分型的系膜增殖、局灶节段病变、球性硬化、炎细胞浸润、间质纤维化、肾小管萎缩、血管壁增厚、小动脉玻变等多个指标相关性分析差异均有统计学意义(P<0.05,部分P<0.01),尤其与肾小管间质损伤各项指标(炎细胞浸润、间质纤维化、肾小管萎缩)显著相关(r均>0.6,P<0.01)。ROC曲线表明血、尿NGAL在IgAN中反映小管间质病变程度方面明显优于Scr和肾小球滤过率(eGFR),血NGAL在反映小管间质病变程度方面比尿NGAL敏感度和特异度更高。结论:血、尿NGAL水平与IgA肾病临床及病理多个指标相关,更能反映肾小管间质损伤程度,可以作为评估IgA肾病小管间质病变的早期无创性指标。     

老年及老年前期IgA肾病的临床病理特征

目的:探讨老年及老年前期IgA肾病的临床病理特征.方法:587例IgA肾病依据年龄分为儿童组、中青年组和老年及老年前期组.对比不同年龄IgA肾病的临床病理资料.结果:35例老年及老年前期IgA肾病以肾病综合征为主,占48.6%,其次为孤立性肉眼血尿(17.1%),以LeeⅣ及Ⅴ级为主,占48.6%,肾小球节段和/或球性硬化的发生率高达77.0%,间质纤维化91.4%,免疫病理以IgAMG型及IgAG型为主,伴高血压者肾小管间质病变指数较高.高血压、肾衰竭发生率较儿童及中青年组患者高,而血尿的发生率较低.高脂血症较中青年组多见.与儿童相比,其FsGs比例较高,病理半定量分析显示其肾小球硬化指数较高,间质纤维化发生率及程度较高,间质炎细胞浸润较明显,肾小管-间质指数较高,但与中青年组相比则无统计学差异.结论:老年及老年前期IgA肾病具有一定的临床病理特征,慢性病变多见,肾小管间质病变重,高血压、高脂血症及生理性退变等可能为其主要介导因素.     

MCP-1在IgA肾病肾组织中的表达与临床病理关系

目的 研究MCP-1在人类IgA肾病肾组织中的表达,进一步了解MCP-1与IgA肾病临床病理关系,并探讨其在IgA肾病进展中的可能作用机制.方法 根据IgA肾病病理半定量评分系统中8个病理指标评分标准,给予IgA肾病组按照病变程度赋予分值,采用SP免疫组织化学方法检测正常对照组和Iga肾病组肾组织中MCP-1的表达,探讨MCP-1与IgA肾病临床病理关系.结果 (1)在正常肾组织中,MCP-1表达较弱,正常对照组与IgA肾病组肾组织中MCP-1表达量均有统计学差异(P＜0.05);(2)IgA肾病肾组织中MCP-1表达量与IgA肾病组织学半定量评分法8个病理指标中破坏肾小球毛细血管袢活动性指数(dGAI)、系膜细胞增生指数(MsHI)、系膜基质增多指数(MsMI)、肾小球慢性病变指数(GCI)、肾间质炎症细胞浸润指数(infI)、肾小管萎缩和肾间质纤维化指数(TCI)等6个指标正相关(P＜0.05),而与内皮细胞增生指数(endol)、小动脉慢性病变指数(VCI)无明显相关性(P＞0.05);IgA肾病肾组织中MCP-1表达量与患者的蛋白尿水平正相关、肌酐清除率水平负相关(P＜0.05),而与患者血尿水平无明显相关性(P＞0.05).结论 在IgA肾病组肾组织中,MCP-1表达量与反映肾小球硬化、肾小管间质纤维化和细胞外基质积聚的病理指标呈正相关,提示其在IgA肾病病情进展中起重要作用.在IgA肾病组肾组织中,MCP-1表达量与蛋白尿呈正相关、肌酐清除率呈负相关,提示其与IgA肾病肾功下降、预后不良有关.     

儿童IgA肾病肾小管间质损害与其他临床病理指标的关系探讨

目的:探讨在儿童IgA肾病中肾小管间质损害与其他临床及病理指标的关系。方法:回顾性分析2014年01月~2017年09月在我院肾活检确诊的119例原发性IgA肾病患者的资料,对比不同程度及类型的肾小管间质损害与其他临床及病理指标之间的关系。结果:肾间质损害总体程度与年龄、性别、体块指数、肉眼血尿发生率、内皮细胞增生程度、肾小球硬化分值、纤维型新月体的发生没有关系。随着肾间质损害的加重,肾小球系膜细胞及基质增殖程度、细胞型及混合型新月体的发生率、尿蛋白的排出量逐渐增高同时肾小球滤过率逐渐下降。间质炎性细胞浸润与内皮细胞增生及细胞型新月体的发生关系密切,而存在肾小管萎缩和肾间质纤维化的患者更容易出现肾小球硬化。结论:IgA肾病患儿的肾小管间质损害与肾小球病变程度相平行,其与肾小球系膜细胞及基质增生程度、新月体形成、与蛋白尿及肾小球滤过率的改变密切相关。不同的小管间质病理类型与其他病理指标的关系各有区别但与各项临床指标的关系没有差别。     

IgA肾病肾小管周围毛细血管的变化及临床意义

目的：探讨IgA肾病患者肾小管周围毛细血管与血管内皮细胞生长因子（VEGF）及其受体VEGF-R2（Flk-1）的表达变化及临床意义.方法：对24例不同病理改变的IgA肾病肾组织进行序列切片.采用免疫组织化学SP法检测肾小管间质中VⅢ因子、VEGF和Flk-1的表达.对各指标之间与临床病理改变之间进行相关分析.结果：IgA肾病患者肾组织中,肾小管间质中微血管密度在中度病变的病人表达最多,在重度者表达最少（P〈0.05）.VEGF主要表达于肾小管上皮细胞,Flk-1主要表达于肾间质中肾小管周围毛细血管内皮细胞.两者与肾小管周围毛细血管密度呈正相关（P〈0.05）.在中、重度组肾小管间质肾小管周围毛细血管的微血管密度与患者尿NAG酶的含量呈负相关（r=-0.57,P〈0.05）,与间质纤维化呈负相关性（r=-0.82,P〈0.01）.结论：IgA肾病肾小管周围毛细血管密度变化与肾小管间质的病变密切相关.血管内皮细胞生长因子可能是导致肾小管周围毛细血管密度变化的主要原因.     

单纯性肾小球性血尿90例临床和病理分析

目的分析成人单纯性肾小球性血尿临床和病理特点，探讨血尿类型与病理严重程度的关系，寻找能较好反映单纯血尿患者肾脏病变程度的指标。方法选取90例单纯性肾小球性血尿患者为研究对象，分析不同病理类型的临床和病理特点；比较不同血尿类型以及不同肾小管间质损害程度患者的临床和病理学指标。结果90例患者中IgA肾病32例、局灶增生性肾小球肾炎27例，为最主要的病理类型。镜下血尿组各指标中除球性硬化、血管玻璃样变及IgA沉积外，其余各临床与病理指标均与肉眼血尿组无明显统计学差异。随着单纯血尿患者肾小管间质损害程度的加重，各病理参数积分均显著增加。结论成人单纯性血尿最主要的原因是IgA肾病，病理类型以局灶增生性肾小球肾炎最多见。不能单纯以血尿类型来判断肾脏病理严重程度。肾小管间质损害可以反映单纯性血尿患者的病变程度。     

尿Ⅳ型胶原浓度与IgA肾病肾组织损害的关系

目的:观察IgA肾病(IgAN)患者尿Ⅳ型胶原(Col-Ⅳ)浓度及其与肾组织Col-Ⅳ表达和肾脏病理之间的关系,以期寻找一种能反映IgAN肾损害的非创伤性临床检测指标.方法:ELISA法测定IgAN患者血、尿Col-Ⅳ浓度;免疫组化法检测肾组织Col-Ⅳ表达;应用计算机病理图像分析系统对肾小球基质基底膜面密度、小球细胞个数及肾小管间质病变程度进行半定量分析,观察尿Col-Ⅳ浓度与IgAN患者肾组织Col-Ⅳ表达及肾病理损伤的关系.结果:IgAN患者尿Col-Ⅳ浓度、肾组织Col-Ⅳ表达较健康人明显增高,尤其是增生硬化和间质纤维化显著者更为明显;尿Col-Ⅳ浓度与肾组织Col-Ⅳ表达、肾小球基质基底膜面密度、小管间质损害显著正相关,且在轻度细胞外基质积聚和小管间质损害时,尿Col-Ⅳ浓度即增高;与小球内细胞个数呈负相关,而与肾小球系膜区、毛细血管襻区免疫球蛋白IgA、IgG、IgM和C3沉积的量和沉积范围无关,与血Col-Ⅳ水平无显著相关.结论:IgAN患者尿Col-Ⅳ浓度明显增高,尿Col-Ⅳ水平可作为监测IgAN患者早期肾硬化的一项指标.     

正常血压IgA肾病患者动脉病变的意义

目的:传统观点认为动脉硬化与高血压有关。然而,部分IgA肾病患者,尽管血压正常,但仍有动脉硬化的改变。本研究的目的就是比较血压正常、伴有和不伴有动脉病变的IgA肾病患者的临床病理特点,探讨正常血压IgA肾病患者肾内动脉病变的影响因素及意义。方法:所有患者均经肾活检诊断为原发性IgA肾病,无高血压病史,肾活检前血压<140/90mmHg。动脉病变的定义为活检肾组织光镜下见动脉壁增厚和(或)动脉玻璃样变。符合标准的105例患者,根据动脉病变的有无分为两组,有动脉病变组52例、无动脉病变组53例,分别比较两组的临床病理特点。肾脏动脉病变的半定量分级标准:0:无损害;1:<25%;2:≥25%,<50%;3:≥50%。统计学方法:分别比较两组的临床病理特点,将差异有统计学意义的单因素指标作为多因素分析的入选指标,采用逐步回归方法分析动脉病变的影响因素,以P<0.05作为差异有统计学意义。结果:与无动脉病变组比较,动脉病变组肾活检时的年龄、血肌酐、血尿酸、尿蛋白定量、尿NAG酶、肾小球硬化、肾小管萎缩以及肾间质纤维化的程度显著增高,尿渗透压显著下降。多因素分析的结果表明,肾活检时的血肌酐、尿渗透压、肾小管萎缩及肾间质纤维化是正常血压IgA肾病动脉病变的独立影响因素。动脉病变的程度与血肌酐、肾小管萎缩及肾间质纤维化呈正相关;与尿渗透压呈负相关。结论:血压正常IgA肾病患者的肾内动脉病变,主要与年龄、血肌酐、血尿酸增高等因素有关,常伴有肾小管间质损害。     

RGC-32在儿童IgA肾病肾组织中的表达及意义

目的 研究RGC-32（response gene to complement 32）在IgA肾病(IgAN) 儿童及正常肾组织中的表达及其意义。 方法 用免疫组织化学方法观察IgAN儿童及正常肾组织中RGC-32蛋白的表达与分布,并与α平滑肌肌动蛋白(α-SMA)、转化生长因子β1（TGF-β1）的表达、IgAN肾组织病理损伤程度及临床相关指标进行统计学分析。 结果 RGC-32蛋白在IgAN及正常肾组织的肾小管均明显表达,而在肾小球、肾小管间质及肾血管未见表达。RGC-32 在正常肾组织、IgAN轻度、中度及重度损伤组中的阳性表达指数分别为（18.29±6.22）%、（23.90±9.65）%、（31.23±9.86）%和（34.52±10.63）%。RGC-32在IgAN儿童肾组织的阳性表达指数与肾小球评分、肾小管间质评分均呈正相关（r = 0.385,0.347,P < 0.05）;与α-SMA、TGF-β1表达亦呈正相关（r = 0.594,0.521,P < 0.01）;而与Scr、尿NAG/Cr、尿Alb/Cr、尿 IgG/Cr、尿α1微球蛋白/Cr均无相关（r = 0.117,-0.115,-0.138,-0.176,-0.028,P均>0.05)。 结论 首次发现RGC-32蛋白在IgAN儿童和正常肾组织中表达于肾小管,而在肾小球、肾小管间质及肾血管未见表达。RGC-32可能参与了IgAN患儿的肾小管间质损伤,尤其是TGF-β1诱导的肾小管上皮细胞-间充质转分化（EMT）过程。     

Relationship between intermedin and renal interstitial capillary loss in IgA nephropathy patients

Objective To explore the relationship between intermedin (IMD) and renal interstitial capillary loss in IgA nephropathy (IgAN) patients. Methods Renal biopsy specimens collected from primary IgAN patients in our hospital (n=80) were compared with normal renal tissues. Expressions of IMD, CD31 and VE-cadherin were examined by immunohistochemical method, and plasma concentrations of IMD and TGF-β1 in 37 cases from the 80 cases were compared. The relationship between IMD and renal interstitial capillary loss in IgAN patients was analyzed. Results IMD and VE-cadherin in renal tubule interstitium expressions increased compared to the control group at the early stage of IgAN (P＜0.05). CD31 expression remained unchanged at the early stage of pathological lesions of IgAN (P＞0.05), but decreased at the early stage of clinical stage of IgAN compared to the control (P＜0.05). Expressions of IMD, CD31 and VE-cadherin were reducing as the disease progressed, and the correlations of CD31 and VE-cadherin (r=0.517, P＜0.01), IMD and CD31 (r=0.655, P＜0.01) or IMD and VE-cadherin (r=0.576, P＜0.01) were positive. Plasma concentrations of IMD and TGF-β1 were higher than those of the control group at the early stage of IgAN (P＜0.05), and the changes of IMD and TGF-β1were correlated positively (r=0.582, P＜0.01). Conclusion Compared with the control group, expression of IMD in kidney tubules increases at the early stage of IgAN, and change of IMD correlates closely with the renal interstitial capillary loss. Plasma concentrations of IMD and TGF-β1 increase compared with the control group at the early stage of IgAN, and the changes of IMD and TGF-β1 are related closely.     

Renal interstitial tenascin immunostaining and immune cell infiltration in IgA nephropathy

SUMMARY: Interstitial expression of tenascin and interstitial leucocyte infiltration were examined by an indirect immunoperoxidase method using monoclonal antibodies against tenascin, CD45 (all leucocytes), CD45RO (T cells) and CD68 (monocytes/macrophages) on renal biopsy specimens from 25 patients with mesangial proliferative IgA-positive glomerulonephritis (IgAN). Ten biopsy kidney specimens, which were removed because of renal trauma, were used as the control group. In patients with IgAN, the mean interstitial expression of tenascin was significantly higher than in the control group. Strong tenascin staining was detected in areas with interstitial damage. In patients with IgAN there were positive correlations between the interstitial expression of tenascin and the relative interstitial cortical volume, as well as serum creatinine. In the IgAN patents, a significant increase in the total number of interstitial CD45-immunopositive cells, CD45RO-positive and CD68-positive cells was seen compared with the control group. In patients with IgAN, immunostaining of tenascin did not correlate with the number of T-cells, monocytes/macrophages or all leucocytes in the renal interstitium. These results suggest that in patients with IgAN the interstitial accumulation of tenascin did not depend on the type or the density of interstitial inflammatory infiltrates.     

In situ hybridization studies of stromelysin and tissue inhibitor of metalloproteinase 1 in IgA nephropathy

Summary: Accumulation of the extracellular matrix (ECM) in IgA nephropathy (IgAN) is thought to cause deterioration of glomerular function. Stromelysin and tissue inhibitor of matrix proteinase 1 (TIMP1) may play an important role in the turnover of the glomerular ECM. However, the expression of these enzymes in human renal tissues remains undefined. In the present study, non-radioactive in situ mRNA hybridization, which permitted the analysis at a cellular level, was performed to localize stromelysin and TIMP1 in renal tissue of IgAN. We also determined the percentage of cells positive for stromelysin or TIMP1 mRNA among intraglomerular cells. A total of 16 patients with IgAN were examined, including eight patients with severe histopathological changes and eight with mild changes. Three patients without glomerular disease were also studied. Stromelysin and TIMP1 mRNA were weakly expressed in the mesangium of normal kidneys and IgAN renal tissues with mild damage. However, the expression of both mRNA was significantly increased in the area of mesangial proliferation, in glomerular epithelial cells and in Bowman's capsule of advanced lesions. Several cells in the area of mesangial proliferation were double positive for stromelysin and TIMP1 mRNA, while certain cells positive for stromelysin mRNA did not express TIMP1 mRNA. In the interstitium, epithelial cells of certain tubules and some mononuclear cells were positively stained for these mRNA, especially in advanced lesions. Our results indicated that stromelysin and TIMP1 genes were expressed in glomerular resident cells, tubular epithelial cells and infiltrated mononuclear cells in IgAN, and their expression was enhanced in advanced tissue damage. the demonstration of a co-expression and discordant expression of the genes indicates that each gene expression may be regulated in a cell type-specific manner and that it could also be altered by cellular environmental factors.     

Evaluation of Renal Clinicopathological Changes in IgA Nephropathy by Urinary Podocytes Excretion and Podocalyxin Expression

Objective: To explore the association of urinary podocyte excretion and renal expression of podocyte-specific marker podocalyxin (PCX) with clinicopathological changes in immunoglobulin A nephropathy (IgAN). Methods: Morning urine samples from IgAN patients and healthy controls were collected. The expression of glomerular PCX was quantified in 50 IgAN patients diagnosed by renal biopsy. IgAN was classified based on the Lee’s Grading system and scored according to the Katafuchi semiquantitative criteria. Morphological evaluation of podocyte was determined by electron microscopy. Results: The amount of urinary podocytes in the IgAN patients was significantly higher than that in the healthy controls (p < 0.01). Pairwise comparison among Lee’s grades of IgAN showed that the median of urinary podocytes in Lee’s I–II group was lower than that in Lee’s III, IV, and V groups (p < 0.05); group III lower than group V (p < 0.05). The positive rate of urinary podocytes was the highest in Lee’s IV and V groups (100%), and lowest in Lee’s I–II group (55%). Multiple comparison among groups of Lee’s grades of IgAN showed that the glomerular PCX expression in Lee’s I–II group was higher than that in Lee’s III, IV, and V groups (p < 0.05); groups III and IV higher than group V (p < 0.05). The amount of urinary podocytes in IgAN patients was negatively correlated with PCX expression (r = ?0.702, p < 0.01), but positively correlated with 24-h urinary protein (r = 0.465, p < 0.01) and glomerular (r = 0.233, p < 0.01) and renal tubular pathological scores (r = 0.307, p < 0.05). The glomerular PCX expression was negatively correlated with 24-h urinary protein (r = ?0.367, p < 0.05) and glomerular (r = ?0.560, p < 0.05) and tubular pathological scores (r = ?0.377, p < 0.05). Electron microscopy showed significant changes in podocytes of IgAN, especially in the foot process. Conclusion: The amount of urinary podocyte can reflect the loss of podocytes in renal tissue, which may be a marker of IgAN progression.     

Impact of microvascular injury on IgA nephropathy associated with malignant hypertension: a preliminary study

ObjectiveTo observe the vascular lesions of renal small arteries and arterioles as well as clinco - pathological characteristics among patients with IgA nephropathy associated with malignant hypertension (IgAN-MHT). To explore the clinical significance of peritubular capillary (PTC) loss and renal tubulointerstitial macrophage infiltration in the same population. MethodsThirty - four (1.9%) IgAN-MHT patients were diagnosed among the 1765 cases of primary IgA nephropathy in Peking Union Medical College Hospital from January 2003 to March 2012. Their clinical records were reviewed and the lesions of glomeruli, tubules, interstitium and renal vessels were semi-quantitatively re-evaluated. PTC and renal tubulointerstitial macrophages were demonstrated by immunohistochemical staining. ResultsThe IgAN-MHT patients were mainly young males with very high blood pressure. They had variant renal function impairment and urinary protein excretion. Acute and chronic vascular changes coexisted in the renal small arteries and arterioles, but all the vascular lesions failed to correlate with renal function. The renal tubulointerstitial macrophage infiltration was prominent and correlated well with renal function. PTC loss was also prominent and the PTC proportion was correlated with renal function. ConclusionsIn IgAN - MHT patients, the renal vascular changes do not correlate with renal function, but PTC loss and renal tubulointerstitial macrophage infiltration are both prominent and may reflect renal function impairment.     

TNF-α-mediated podocyte injury via the apoptotic death receptor pathway in a mouse model of IgA nephropathy

BackgroundIgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and it is characterized by mesangial IgA deposits. Proteinuria is a common clinical feature of IgAN, which has a critical connection to podocyte injury and has been used as a clinical prognostic factor for IgAN. Evidence has shown that TNF-α released from mesangial cells may lead to podocyte apoptosis.MethodsForty male BALB/c mouse were randomly divided into the control group and IgAN group. A mice model of IgAN was developed by oral administration of bovine serum albumin (BSA) combined with Staphylococcus Enterotoxin B (SEB) tail vein injection. Urinary protein concentrations, renal function, renal morphological, IgA deposition, apoptosis situation, and the mRNA and protein expression of nephrin, podocin, TNF-α, TNFR1, caspase-8 and caspase-3, were detected after 12 weeks.ResultsBSA and SEB can successfully establish an IgAN mouse model, and the main pathological changes are the IgA immune complex deposition in the mesangial area. The gene and protein expression levels of nephrin and podocin were found to be downregulated, and death receptor pathway-related indicators were upregulated, and they were involved in TNF-α-activated podocyte injury and apoptosis in IgAN mice.ConclusionTNF-α may play an important role in the pathogenesis of podocyte apoptosis in IgAN, and its effects may be mediated through the apoptotic death receptor pathway.     

制大黄-川芎药对对造影剂肾病大鼠肾小管上皮细胞凋亡的影响

目的：探讨制大黄-川芎药对对造影剂肾病（CIN）大鼠肾小管上皮细胞凋亡的影响及机制。方法：将32只雄性SD大鼠分为正常组（A组）、模型组（B组）、药对高剂量组（C组）、药对低剂量组（D组）。C、D组于造模前7天每日灌胃药对水煎液,灌胃量分别为成人标准体重（60kg）常规用量50、20倍。造模后24h处死动物,测定血清肌酐、尿素氮,HE染色观察肾脏病理改变,TUNEL染色检测肾小管上皮细胞凋亡,western印迹检测肾组织Caspase-3表达。结果：建模后24h与A组相比,B组血清肌酐、尿素氮均明显升高（P〈0.01）;病理形态学检测提示模型大鼠发生明显肾间质水肿、肾小管上皮细胞胞浆空泡样变、肾小管上皮细胞凋亡（P〈0.01）,Caspase-3蛋白表达显著增多（P〈0.01）。与B组相比,C、D组血清肌酐、尿素氮明显回落（P分别〈0.01or〈0.05）,肾脏病理改变显著为轻,肾小管上皮细胞凋亡指数显著减少（P〈0.01）,Caspase-3蛋白表达明显降低（P〈0.01）。结论：caspase3依赖的肾小管上皮细胞凋亡参与了大鼠造影剂肾病的发生,制大黄-川芎药对能通过抑制caspase3抑制肾小管上皮细胞凋亡,并进而保护CIN大鼠肾功能。     

GMP-17-positive T-lymphocytes in renal tubules predict progression in early stages of IgA nephropathy

Treatment of patients with IgA nephropathy (IgAN) depends on a reliable assessment of disease progression based on measurements of glomerular filtration rate (GFR), proteinuria, hypertension, and tubulointerstitial changes. We sought to determine whether progression could be predicted from analysis of glomerular and tubulointerstitial inflammation in biopsies taken at an early stage of IgAN. We retrospectively analyzed biopsies from 50 patients, relating the subsequent clinical course to infiltration with B- and T-lymphocytes, granule membrane protein of 17 kDa (GMP-17) positive cytotoxic T cells, macrophages, fibroblasts, and tubulointerstitial expression of human leukocyte antigen-D related (HLA-DR). At biopsy, 19 patients had decreased GFR while 13 of 31 patients with normal GFR and progressive IgAN differed significantly from 18 non-progressors in the level of proteinuria and in the severity of scores for mesangial proliferation, tubular atrophy, interstitial fibrosis, and interstitial infiltrates. On multivariate regression analysis these differences disappeared; however, associations with GMP-17-positive cytotoxic T-lymphocytes in intact renal tubules and of B-lymphocytes in the interstitium remained significant. Our study may have identified a marker of disease progression in early stages of IgAN.     

Clinical significance of costimulatory molecules CD80/CD86 expression in IgA nephropathy

BACKGROUND: IgA nephropathy (IgAN) is the most common form of human glomerulonephritis. Tubulointerstitial inflammation with infiltration of mononuclear cells plays an important role in the progression of IgAN. Activation of T cells requires costimulatory signals through binding of CD28 receptor with cognate ligands (CD80/CD86) located on antigen-presenting cells (APC). To assess the clinical significance of this regulatory pathway participation in the pathogenesis of IgAN, a comprehensive immunohistologic evaluation was conducted on renal tissue of IgAN in different phases of progressive injury. METHODS: Thirty-three cases of IgAN and ten cases of non-IgA mesangial proliferative glomerulonephritis (PGN) with minor tissue damage as controls were investigated. Monoclonal antibodies were used to assess the expression of CD80, CD86, CD68, CD14, CD45RO, human leukocyte antigen-DR (HLA-DR), and intercellular adhesion molecule-1 (ICAM-1) in renal tissues. Clinical and expression data were compared at the time of renal biopsy. RESULTS: CD80+ and CD86+ cells were observed more in IgAN patients with progressive renal injury than in mild cases and controls. CD80 was limited to tubular epithelial cells and was complemented by HLA-DR expression. CD86 was expressed in the glomerulus, periglomerular area, and peritubular interstitium. Activated T cells (CD45RO+), monocytes (CD14+), macrophages (CD68+), and CD86 showed similar distributions. Positive correlations were found between CD86+ cells and CD45RO, CD14, and CD68 positive cells and between CD80+ tubuli and peritubular interstitial CD45RO+ cells. The number of interstitial CD86 positive cells and the percentage of CD80+ tubuli were correlated with renal function. Most CD86+ cells were monocyte/macrophages. CONCLUSION: This study suggested that CD80 and CD86 activate T cells in IgAN, CD80/CD86 expressions correlated with renal function at the time of renal biopsy, and monocyte/macrophages and tubular epithelial cells act as APC.