狼疮方对狼疮样小鼠肾脏RANTES表达的影响

目的 :观察慢性移植物抗宿主病 (GAHD)狼疮样肾炎小鼠模型肾组织中趋化因子RANTES的表达并探讨中药狼疮方对其的影响。方法 :以强的松为阳性对照 ,观察狼疮方对模型小鼠肾脏RANTES表达的影响 ,并进一步分析其对肾脏病理和功能损害的影响。结果 :狼疮方具有与强的松相似的防止和减轻狼疮样肾炎小鼠肾功能恶化、肾组织病理改变的作用(P <0 0 0 1)。这作用与减轻狼疮小鼠肾组织中RANTES表达显著相关。结论 :狼疮方明显下调狼疮肾炎肾脏RANTES表达 ,这与其减轻病理改变相一致     

狼疮肾炎小鼠肾脏的比较蛋白质组学研究

目的探讨狼疮肾炎(LN)小鼠肾脏和正常小鼠肾脏蛋白质组的差异。方法应用双向凝胶电泳技术(two-dimensional gel electrophoresis,2-DE)分离肾组织总蛋白质,凝胶用银染显色,扫描仪获取凝胶图像并对其进行软件分析。结果同组实验重复3次,其中正常对照组3张图找到蛋白质点平均573±52个,匹配率为83%;LN组找到蛋白质点平均658±43个,匹配率为87%。经软件分析,LN组和对照组比较表达增加大于2倍的点有119个;降低大于0.5倍的点有140个。结论LN小鼠肾脏蛋白质表达发生了显著变化,这可能和LN的发生发展有着密切关系。     

柴胡皂甙d对狼疮肾炎小鼠肾组织病变改善作用的研究

目的观察柴胡皂甙d(saikosaponin-d,SSd)对NZBWF1狼疮肾炎小鼠尿蛋白含量及肾组织病变改善作用的影响。方法将雌性NZBWF1小鼠随机分为3组:①Ⅰ组(SSd治疗1组),SSd剂量0.2mg.100g-1.d-1;②Ⅱ组(SSd治疗2组),SSd剂量0.4mg.100g-1.d-1;③Ⅲ组(空白对照组);共治疗6周。用考马斯亮蓝法检测小鼠尿蛋白含量,用光镜、电镜和免疫荧光检查小鼠肾组织学变化。结果实验2周、4周以及6周末,SSd治疗1组和SSd治疗2组尿蛋白含量明显低于空白对照组(P<0.05);SSd治疗2组尿蛋白含量显著低于SSd治疗1组(P<0.05)。实验6周末观察,与空白对照组比较,SSd治疗组小鼠肾小球内皮细胞和系膜细胞增生,透明变性、渗出以及足突融合现象得到改善,肾小管受损百分比降低,内皮下、上皮下以及系膜区电子致密物沉积等病理改变都有不同程度的改善。免疫荧光检查结果显示SSd治疗组IgG、IgA以及IgM在肾小球系膜区和肾小球毛细血管壁的沉积比空白对照组明显减少。结论SSd对NZBWF1自发狼疮肾炎小鼠有治疗作用,能够减少尿蛋白含量,和改善狼疮肾炎小鼠肾组织病变。     

MIP-1α在狼疮肾炎患者肾组织的表达及意义

目的 :检测狼疮肾炎 (LN)患者肾组织巨噬细胞炎症蛋白 1α(macraphageinflammatoryprotein 1αMIP 1α)mRNA表达情况并探讨其与临床病理间的关系。方法 :原位杂交方法检测肾组织MIP 1αmRNA表达。结果 :正常肾组织未见MIP 1αmR NA表达 ,LN肾组织MIP 1αmRNA表达于肾小球内、皮质小管上皮细胞及间质 ,IV型LNMIP 1α表达尤明显。LN肾小球、肾小管及间质MIP 1α表达与LN病理活动指数正相关 ,与 2 4h尿蛋白无显著相关 ,与LN病理慢性指数、Scr无显著相关。结论 :MIP 1αmRNA在LN肾组织表达增强 ,尤以IV型为著 ,其表达与肾小球及间质小管活动性炎症损害相关。     

早期狼疮肾炎患者血中sCD40L水平的变化及其意义

系统性红斑狼疮(systemic lupus erythematosus，SLE)是最常见的一种风湿性疾病，狼疮肾炎(1upus nephritis，LN)为其最常见的脏器损伤，也是导致SLE患者死亡的重要原因之一。因此，探讨其发病机制已成为风湿性疾病研究的重要课题。近年来，人们对共同刺激信号CD40—CD40L在SLE发病中的作用十分重视。本研究旨在探讨早期LN患者血中可溶性CD40配体(sCD40L)水平的变化及其在该病发病中的作用。     

IL-12对狼疮肾炎PBMC中信号传递分子STAT_3、STAT_4的作用

目的 :为了探讨IL 12对狼疮肾炎PBMC发挥生物学作用的细胞内信号传递机制。方法 :采用MTT、免疫沉淀、免疫印迹等方法 ,检测IL 12对PBMC增殖及STAT3、STAT4的作用 ,并比较在狼疮肾炎活动期、静止期的差别。结果 :发现与正常人对照及静止期相比 ,IL 12对活动期PBMC不需要IL 2的预诱导 ,可促进PBMC增殖并在短时间内激活STAT3、STAT4,而IL 2对STAT4无作用。结论 :表明IL 12对PBMC的作用可通过STAT3、STAT4途径发挥 ,活动期PBMC存在异常活化 ,这可能是IL 12促进狼疮肾炎PBMC参与发病的细胞内机制之一     

中药狼疮方对狼疮样BXSB小鼠肺组织CD134/CD134L和RANTES表达的影响

目的探讨中药狼疮方对狼疮样BXSB小鼠肺组织CD134／CD134L和RANTES表达的影响。方法采用BXSB小鼠模型,随机分为3组：狼疮方治疗组、强的松治疗组、未治疗组,每组6只,疗程10周。另设与BXSB小鼠同基因的正常C57BL／6小鼠6只为正常对照组。分别取小鼠肺组织,应用逆转录-荧光定量-聚合酶链反应（RT-FQ-PCR）技术定量测定小鼠肺组织CD134、CD134L和趋化因子RANTES的mRNA表达水平。结果①未治疗组小鼠肺组织CD134、CD134L mRNA和RANTKS mRNA的表达水平都显著高于正常对照组（P〈0．01,P〈0．05）;经强的松或中药狼疮方治疗后,BXSB小鼠肺组织CD134、CD134L及RANTES的mRNA表达都受到明显抑制,显著低于未治疗组（P〈0．01,P〈0．05）;且接近正常水平,与正常对照组无显著性差异（P〉0．05）。②BXSB小鼠肺组织RANTES的mRNA表达水平与CD134L的mRNA表达水平呈显著的正相关关系（r=0．793,P〈0．05）,而与CD134的mRNA表达水平无显著的相关关系（r=0．412,P〉0．05）。结论中药狼疮方具有与强的松类似的免疫抑制作用,可显著抑制狼疮样小鼠肺组织CD134／CD134L共刺激信号表达;并下调肺组织RANTKS mRNA表达水平,具有一定的肺脏保护作用。     

单核细胞骨调素的表达水平与狼疮肾炎

目的：研究骨调素（OPN）在狼疮性肾损害中的作用。方法：采用酶联免疫吸附试验（Ⅱ届A）检测了90例系统性红斑狼疮（SLE）患者、15例非SLE肾损害患者及30例对照血浆OPN的水平，应用半定量RT-PCR方法，测定以上各组外周血单个核细胞（PBMCs）OPN的表达。结果：狼疮处于疾病活动时PBMCs OPN mRNA表达上调，尤其是狼疮肾炎活动组患者PBMCs OPN mRNA表达增加最为显著（P〈0．01），PBMCs OPN mRNA表达不仅与总狼疮疾病活动指数评分呈正相关（r=0．532，P〈0．001），而且与狼疮疾病活动指数肾评分呈正相关（r=0．584，P〈0．001），而非狼疮肾脏疾病组仅低水平表达，与正常对照组水平相近似（P〉0．05）。狼疮活动组血清OPN水平较非活动组及正常对照组均明显升高（P〈0．01），但活动性狼疮肾炎组与无肾损伤组之间血清OPN水平的差异无显著性（P〉0．05）。结论：狼疮处于疾病活动时PBMCs OPN mRNA表达上调，并与狼疮肾炎的疾病活动情况密切相关。     

狼疮肾炎患者血中巨噬细胞衍生趋化因子和IL-18水平的变化及意义

目的:探讨不同病理类型的狼疮肾炎(LN)患者血中巨噬细胞衍生趋化因子(MDC)和白介素18(IL-18)的变化及意义。方法:应用ELISA法对不同病理类型LN患者血中MDC和IL-18进行测定。结果:(1)Ⅱ、Ⅲ型LN患者血中MDC的水平明显增高。MDC的水平与LN患者血中补体的变化呈负相关,与抗ds-DNA抗体的变化呈正相关,与系统性红斑狼疮的疾病活动评分(SLEDAI)呈正相关。(2)IL-18的水平在Ⅱ、Ⅲ、Ⅳ型LN患者血中均明显增高,且与补体下降呈负相关,与抗ds-DNA抗体水平、SLEDAI评分及LN患者的肾功异常呈正相关。③MDC的水平在Ⅱ、Ⅲ型LN组与IL-18水平的变化呈正相关,在Ⅳ型LN组无明显相关变化。结论:MDC和IL-18在LN的发生发展中均有重要作用,MDC对病变过程中的病理损伤的程度及Th1/Th2细胞失衡的变化的探讨具有重要意义。IL-18在LN的发生发展、治疗及预后的监控上具有重要作用。     

138例狼疮性肾炎肾穿刺材料分析

报告138例肾穿刺活检狼疮性肾炎(LN)的病理变化,并讨论其病理诊断、分型及临床病理联系。138例中系膜增生型23例,局灶增生型14例,弥漫增生型72例,膜型25例,硬化型4例,以下病变提示LN:①肾小球病变多样性,②肾小管萎缩、间质炎症和(或)局部有免疫复合物形成,③电镜下见内皮下、基膜内、上皮下、系膜区广泛电子致密物沉积。苏木素小体具诊断意义,其阳性率为18.8%。肾组织局部HBsAg阳性率达57.8%.文章讨论了HBV感染和SLE发病的关系。     

Fate of full‐house immunofluorescence staining in renal allograft: A case report

Here, we report the case of a patient with renal allograft with full‐house immunofluorescence staining in the zero‐hour biopsy. Full‐house immunofluorescence staining is a well‐known characteristic of lupus nephritis. Previous studies have reported patients with full‐house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full‐house nephropathy. We identified only one case out of 2203 zero‐hour biopsies over 13 years. Zero‐hour biopsy presented no glomerular changes but showed full‐house immunofluorescence staining. Electron microscopy revealed a nonorganized electron‐dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)‐associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1–3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis.     

Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare

Objective: To explore a new predictor of renal flares after successful inductive treatment for diffuse proliferative glomerulonephritis(DPGN) in patients with lupus nephritis. Methods: A cohort of patents with SLE DPGN who were treated initially with prednisone and cyclophosphamide were studied. Those who responded to inductive treatment were followed up for the occurrence of renal flares. Urinary levels of RANTES, MCP-1 and M-CSF were measured by ELISA. Other clinical and laboratory data were collected. The predictors and outcome of renal flare were analyzed. Results: Seventy-three qualified patients with SLE DPGN were investigated. After a mean follow-up of 24.5 ± 6.4 months, 22 patients experienced renal flares. The median time to relapse was 14.1 ± 4.1 months. The patients experiencing renal flare showed higher urinary RANTES, MCP-1 and M-CSF. However, independent predictors of renal flares were increased urinary RANTES and M-CSF. Eight patents developed doubling of the serum creatinine (CRX2) level. The occurrence of renal flares was the only predictor of CRX2. Conclusions: Persistently increased urinary levels of RANTES and M-CSF after initial remission are predictors of renal flare in patients with SLE DPGN. Our results indicate monitoring urinary pro-inflammatory factors may direct us in managing those patients. Received 6 September 2006; returned for revision 30 November 2006; returned for final revision 23 February 2007; accepted by G. Wallace 19 March 2007     

Renal involvement in systemic lupus erythematosus: glomerular pathology,classification, and future directions

Systemic lupus erythematosus is a common cause of glomerulonephritis. Despite improvements in the management of lupus nephritis, about 10–30% of patients develop end-stage kidney disease within 15 years. The renal biopsy provides crucial information to the clinician, as the choice of treatment is guided by the histopathologic findings. The light microscopic appearances and clinical features of patients with systemic lupus erythematosus can vary considerably, reflecting the many patterns of histopathologic injury seen in this glomerulonephritis. This review illustrates the glomerular pathology and pathogenesis of lupus glomerulonephritis, and will focus on the most recent classification, the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Classification of Lupus Nephritis.     

Ultrastructure of the Kidney in Acute Interstitial Nephritis

Fifteen percutaneous renal biopsies from patients with acute renal failure due to acute interstitial nephritis (AIN), in almost all cases due to drugs, were studied by electron microscopy. Differential counting of interstitial cells showed an average of 69% lymphocytes (small and large) and 11 % macrophages. Plasma cells and eosinophils were comparatively rare. The infiltrate resembled that of acute rejection, suggesting a cellular hypersensitivity reaction. Proximal and distal tubules were severely affected focally. Migration of lymphocytes through the tubular basement membrane of otherwise well-preserved tubules was considered to be the first phase. Other tubules showed extreme thinning of the tubular basement membrane, with still intact cellular walls. Rupture of the tubular basement membrane and necrotic disintegration of tubular epithelial cells are probably late phenomena. The non-necrotic tubules displayed severe reduction of proximal brush border and proximal as well as distal tubular basolateral infoldings. Focal tubular disintegration leading to tubular block and/or backleak as well as decrease of proximal tubular sodium resorption leading to a decreased glomerular filtration (a mechanism probably also acting in ischemic acute renal failure) may all be factors responsible for the acute renal failure in AIN.     

Insulin‐like growth factor binding protein‐2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis

Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Invasive renal biopsy remains the gold standard for the diagnosis and management of LN. The objective of this study is to validate serum insulin‐like growth factor binding protein‐2 (IGFBP‐2) as a novel biomarker for clinical disease and renal pathology in LN. Eighty‐five biopsy‐proven lupus nephritis patients, 18 chronic kidney disease (CKD) patients and 20 healthy controls were recruited for enzyme‐linked immunosorbent assay (ELISA) testing of serum IGFBP‐2 levels. Compared to CKD patients of origins other than lupus or healthy controls, serum IGFBP‐2 levels were elevated significantly in LN patients. Serum IGFBP‐2 was able to discriminate LN patients from the other two groups of patients [area under the curve (AUC) = 0·65, 95% confidence interval (CI) = 0·52–0·78; P = 0·043 for LN versus CKD; 0·97, 95% CI = 0·93–1·00; P < 0·0001 for LN versus healthy controls]. Serum IGFBP‐2 was a potential indicator of both global disease activity and renal disease activity in LN patients, correlated with serum creatinine levels (r = 0·658, P < 0·001, n = 85) and urine protein‐to‐creatinine levels (r = 0·397, P < 0·001, n = 85). More importantly, in 19 concurrent patient samples, serum IGFBP‐2 correlated with the chronicity index of renal pathology (r = 0·576, P = 0·01, n = 19) but not renal pathological classification. In conclusion, serum IGFBP‐2 is a promising biomarker for lupus nephritis, reflective of disease activity and chronicity changes in renal pathology.     

The Clinicopathologic Significance of Endothelial Tubuloreticular Inclusions in Glomerular Diseases

Abstract

Background: The presence of tubuloreticular inclusions (TRIs) in endothelial cells (ECs) always evokes suspicion of an association with underlying viral infections or autoimmune diseases. However, other underlying diseases can be associated with TRI expression. Since identification of the underlying disease is of primary consideration for management of glomerulonephritis (GN), it is important to clarify the clinical significance of TRI expression.

Methods: The authors studied 104 renal biopsy cases having TRI. They investigated their clinicopathological profiles and focused on potential connections with underlying diseases.

Results: Among 104 renal biopsy cases, 62 cases (59.6%) were associated with lupus nephritis (LN) and 20 cases (19.2%) were associated with a viral infection (hepatitis B virus (13), hepatits C virus (4), and human immunodeficiency virus (3)). Other underlying disease groups included membranous GN (MGN) (7), IgA nephropathy (7), Henoch-Schoenlein purpura (HSP) nephritis (2), and others (6). The incidence of TRIs in both LN and viral infections was significantly higher than for other diseases (p?<?0.0001). Among 7 MGN cases, 2 cases were diabetes, 1 case was associated with lung cancer, another case with antineutrophilic cytoplasmic antibody (ANCA), and the others showed no evidence of systemic disease. On immunofluorescence (IF) study, 2 MGN cases, 2 IgA nephropathy cases, and 1 HSP nephritis case showed C1q deposition, with no evidence of SLE.

Conclusions: TRIs were identified in MGN and other glomerular diseases, including IgA nephropathy and HSP nephritis. However, a diagnosis of LN should be considered because TRIs associated with a full-house IF pattern are usually found in LN.     

Association of miRNA-145 expression in vascular smooth muscle cells with vascular damages in patients with lupus nephritis

miRNAs have been found to contribute to the regulation of multiple cellular processes, including cell apoptosis, differentiation and proliferation. The patients with lupus nephritis (LN) exhibit thickened renal vascular membrane and highly proliferative vascular smooth muscle cells (VSMCs). Of various miRNAs discovered, miR-145 is essential to mediate the proliferation of VSMCs and the formation of atherosclerotic plaques. In this study, we studied the pathological and vascular damage of renal LN, and the correlation between miR-145 expression in VSMCs and the vascular damages. Serum, urine, and renal biopsies were obtained from 41 patients with active LN. The serum and urinary VEGF levels were examined to confirm the renal damage of each patient. Biopsies were stained to observe the glomerular segmental lesions, sclerosis, and to evaluate the vascular damages. The expression of miR-145 was also examined to determine the correlation between its expression and the vascular damages. The expression of miR-145 was mainly detected in the renal VSMCs and the epithelial cells of glomerular proximal convoluted tubule. Nevertheless, the expression of miR-145 reduced as the tunicae media vasorum ratios increased, indicating the development of LN inhibits the expression of miR-145. Furthermore, our studies revealed no significant correlation among renal interstitial vascular damage, glomerular damage and severity classification of LN. Therefore, we suggest the damage of renal interstitial vascular should be considered as one of the factors to evaluate the severity of the LN.     

狼疮性肾炎患者血浆中P选择素检测的临床意义

采用双抗体夹心法ＥＬＩＳＡ检测３５例狼疮性肾炎（ＬＮ）患者血浆可溶性粘附分子Ｐ选择素含量，结果发现ＬＮ＇患者血浆Ｐ选择素水平较正常对照增高，其中ＬＮ肾病综合征型和肾功能不全型的上述水平又显高于无症状型和肾炎型。对部分患者进行动态观察，发现经治疗病情改善者血浆Ｐ选择素水平降低。本文证实ＬＮ患者体内不同程度存在内皮细胞、血小板激活状态。检测血浆Ｐ选择素可能对判断或监测ＬＮ患者血栓形成状态、病情进展及活动转归等具有重要意义。     

狼疮性肾炎组织形态学半定量分析及其临床意义

对26例狼疮性肾炎(LN)肾穿刺活检标本组织形态学进行半定量分析,结果表明:LN组织学类型、肾功能状况与活动性指数(AI)、慢性指数(CI)有明显关联。进一步将半定量指数分为三级,发现AI 0～6分的病人很少发生肾功能衰竭(1/13),>10分的病人均发生肾功能衰竭(5/5),7～10分者1/4病人发生肾功能衰竭(2/8)。CI分级不如AI分级敏感。认为LN组织形态学半定量分析,对判断预后、指导治疗可能具有重要意义。