中性粒细胞明胶酶相关脂质运载蛋白在狼疮肾炎小鼠模型中的表达及其意义

目的：探讨中性粒细胞明胶酶相关脂质运载蛋白（NGAL）在 LN 中的表达及其意义。方法36只12周龄的雌性 MRL/lpr 小鼠随机分为实验组和干预组,并以相同周龄的18只雌性昆明小鼠作为对照组。干预组小鼠腹腔注射抗小鼠 IL-17抗体20μg,每2周1次,至实验观察点结束。各组分别于第1次给药后的24 h、14 d 及28 d 处死6只小鼠。 ELISA 法检测小鼠血清 NGAL、IL-17、MMP-9、基质金属蛋白酶组织抑制剂（TIMP）-1的水平,免疫组织化学法检测肾组织 NGAL、IL-17、MMP-9及 TIMP-1的表达水平。组间均数的比较采用单因素方差分析或非参数秩和检验。两因素之间的关系采用 Pearson 相关分析。结果①实验组 MRL/lpr 小鼠血清 NGAL 水平在各时间点均高于对照组和干预组[16周龄（30.31±1.22） ng/ml、（11.36±0.14） ng/ml、（20.09±0.35） ng/ml,F=986.524,P<0.01],血清 IL-17、MMP-9、TIMP-1水平在各时间点也均显著高于对照组和干预组（P 均<0.05）。② NGAL 在实验组小鼠肾小管上皮细胞中的表达明显增强,在各时间点均高于对照组和干预组[16周龄（11.27±0.58）与（0.45±0.19）、（9.22±0.67）,F=15.158, P=0.001],IL-17、MMP-9、TIMP-1在各时间点的表达也均高于对照组和干预组（P 均<0.05）。③在实验组（16周龄）,MRL/lpr 小鼠血清 NGAL 水平和肾脏 NGAL 表达量与 IL-17、MMP-9、MMP-9/TIMP-1水平均呈正相关[血清（r=0.899、0.789、0.925,P<0.01）,肾脏（r=0.929、0.899、0.723,P<0.01）]。结论 NGAL 在MRL/lpr 狼疮小鼠的血清水平与肾组织中的表达均显著增加,并通过与 IL-17、MMP-9等炎性因子的相互作用而参与 LN 的炎症免疫反应。     

MRL/lpr小鼠肾组织CCR4受体表达检测

目的研究CCR4受体在红斑狼疮小鼠肾组织中的表达与作用。方法用逆转录—聚合酶链反应技术（RT-PCR）和蛋白印迹的方法检测在出现狼疮肾炎的MRL/lpr小鼠肾组织中CCR4 mRNA和蛋白水平的表达。结果MRL/lpr小鼠肾组织CCR4 mRNA表达明显升高（P〈0.05）;MRL/lpr小鼠肾组织中可检测出CCR4蛋白条带,而BALB/c小鼠肾脏组织中未能测得。结论CCR4在红斑狼疮小鼠肾脏组织中表达增高,并可能参与介导了小鼠狼疮性肾炎的发病。     

2型糖尿病患者尿液MMP-9及MMP-9／NGAL活性检测及其临床意义

目的探讨2型糖尿病（T2DM）患者尿液中基质金属蛋白酶9（MMP-9）及MMP-9／中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的活性与T2DM的关系。方法应用明胶酶谱法对35例健康人和142例T2DM患者的尿液进行检测。结果（1）急性并发症组尿液中MMP-9及MMP-9／NGAL的活性及其检出率明显高于对照组及单纯糖尿病组（P〈0．01）;（2）慢性并发症组尿液MMP-9及MMP-9／NGAL的活性及其检出率也明显高于对照组（P〈0．01）,肾损害亚组MMP-9活性明显高于无肾损害亚组（P〈0．05）,且其活性随病程呈抛物线型变化趋势。结论通过对MMP-9及MMP-9／NGAL活性的检测,可预测炎症、应激的发生,MMP-9及MMP-9／NGAL可作为糖尿病肾损害的早期诊断指标。     

白杨素对MRL/lpr狼疮小鼠的保护作用及机制研究

目的：基于临床疗效确切的“多靶点”疗法(MT)及其前期疗效机制研究,探究白杨素(CHR)对狼疮性肾炎(LN)的疗效及其对白细胞介素6(IL-6)/信号传导蛋白和转录激活物3(STAT3)信号通路的影响。方法：将12只10周龄MRL/lpr狼疮小鼠随机分为疾病组及CHR治疗组,正常对照组采用C57BL/6小鼠,每组6只。CHR治疗组给予CHR 160 mg/(kg·d)灌胃,MRL/lpr组和NC组给予等量羧甲基纤维素钠(CMC-Na)灌胃,持续给药8周后处死小鼠,称量脾脏重量,评估脾脏指数;酶联免疫吸附测定(ELISA)实验检测尿蛋白/肌酐水平,过碘酸-雪夫(PAS)染色评估肾组织病理损伤程度;实时荧光定量PCR(RT-qPCR)和ELISA检测IL-6的表达和分泌水平,蛋白免疫印迹(Western Blot)和免疫组化染色(IHC)评估肾组织中STAT3蛋白的磷酸化水平。结果：CHR治疗可下调MRL/lpr狼疮小鼠脾重及脾脏指数、抑制尿蛋白/肌酐水平并缓解肾脏病理损伤。此外CHR能够显著抑制IL-6分泌、表达水平及肾组织p-STAT3蛋白表达。结论：CHR对MRL/lpr狼疮小鼠具有...     

狼疮清颗粒对AHN模型大鼠肾功能和MRL/lpr小鼠肾组织NF-κBp65蛋白表达的影响

目的观察狼疮清颗粒对主动型Heymann肾炎(AHN)模型大鼠肾功能的作用及其对MRL/lpr小鼠肾组织NF-κBp65蛋白表达的影响。方法大鼠肾皮质加弗氏完全佐剂腹腔注射建立AHN大鼠模型,应用狼疮清颗粒、泼尼松、狼疮清颗粒联合泼尼松,对AHN模型大鼠进行干预治疗4 w,检测其24 h尿蛋白、尿素氮(BUN)、肌酐(Cr)及肾脏病理学变化,同时对MRL/lpr小鼠干预治疗4 w,Western印迹检测肾组织NF-κBp65蛋白表达。结果与模型组相比,各治疗组均降低AHN模型大鼠尿蛋白、BUN、Cr的水平,不同程度的改善AHN模型大鼠肾组织病理变化;显著降低MRL/lpr小鼠NF-κBp65蛋白的表达,其中以狼疮清颗粒联合泼尼松组(中西医结合治疗组)最为明显。结论狼疮清颗粒对狼疮性肾炎具有一定的治疗作用,其机制可能与抑制肾组织NF-κBp65蛋白表达有关。     

人TIMP-1转基因小鼠随增龄肾组织内血管生成的变化及意义

目的　探讨人基质金属蛋白酶组织抑制物-1（tissue inhibitor of metalloproteinase-1,TIMP-1）对肾脏器官衰老过程血管生成的影响。方法　对3、12、24月龄人TIMP-1转基因小鼠和野生型小鼠肾组织石蜡切片行PASM染色,观察肾组织内微血管密度变化;Western免疫印迹检测TIMP-1、TIMP-2、基质金属蛋白酶（matrix metalloproteinase,MMP）-2、MMP-9、血管内皮细胞生长因子（VEGF）、Ⅲ型和Ⅳ型胶原蛋白质表达;明胶酶谱和反向酶谱分别检测明胶酶和TIMP-1的活性。结果　24月龄时与野生型小鼠相比,转基因小鼠肾小球和肾小管周围的微血管密度降低（P〈0.05）;TIMP-1、Ⅲ型和Ⅳ型胶原蛋白质表达增多（P〈0.05）,而MMP-2、MMP-9和VEGF的表达降低（P〈0.05）;明胶酶谱和反向酶谱结果显示,明胶酶的活性下调（P〈0.05）,而TIMP-1的活性则上调（P〈0.05）。结论　TIMP-1可能通过影响血管生成而促进肾脏器官衰老。 基金 国家重点基础研究发展规划（973项目,2007CB507403）;; 国家自然科学基金创新群体科学基金（30121005）     

肾癌组织中MMP-2、MMP-9及VCAM-1的表达变化及意义

目的探讨肾癌及癌旁肾组织中基质金属蛋白酶-2,9(MMP-2、MMP-9)及血管细胞黏附分子1(VCAM-1)的表达差异。方法采用免疫组化法检测MMP-2、MMP-9及VCAM-1在肾癌及癌旁肾组织中的表达,应用明胶酶图法检测MMP-2及MMP-9在肾癌及癌旁肾组织中明胶酶的活性。结果肾癌组织中MMP-2、MMP-9及VCAM-1的表达阳性率较癌旁肾组织显著升高(P<0.01),肾癌组织中MMP-2及MMP-9的明胶酶活性较癌旁肾组织也呈增高趋势(P<0.01)。结论 MMP-2、MMP-9及VCAM-1在肾癌组织中表达升高,可能促进肾癌的发病及进展。     

MRL/lpr小鼠胸腺异位基因的表达

目的 探讨MRL/lpr狼疮小鼠胸腺多种异位基因表达水平的变化,及其与自身耐受和器官损害的关系.方法 尿蛋白试纸条检测小鼠尿蛋白,间接免疫荧光法检测抗核抗体.RT-PCR检测模型组(MRL/lpr狼疮小鼠)和对照组(BAB/C小鼠)mTECs 4种异位基因(唾液蛋白2、甲状腺球蛋白、组织蛋白酶L和C-反应蛋白)mRNA水平,病理学检测唾液腺的组织学变化.结果 模型组小鼠4种异位基因表达水平均较对照组小鼠降低,差异有统计学意义.模型组出现唾液腺炎的病理损害.结论 MRL/lpr狼疮小鼠异位基因表达降低导致中枢耐受异常是MRL/lpr小鼠发病的原因之一,可能与某些器官损害的发生有关.     

MRL/lpr狼疮鼠中结缔组织生长因子与γ-谷氨酰半胱氨酸合成酶的表达及相关性研究

目的 探讨MRL/lpr狼疮鼠模型中重要的抗氧化因子γ-谷氨酰半胱氨酸合成酶(γ-GCS)在肾纤维化发生过程所起的作用.方法 应用半定量反转录聚合酶链反应(RT-PCR)和免疫组织化学技术,观察MRL/lpr狼疮鼠及正常对照组小鼠肾组织中结缔组织生长因子(CTGF)和γ-GCS的表达,并进一步分析γ-GCS表达量与CTGF之间存在的内在联系.结果 MRL/lpr小鼠模型肾脏CTGF mRNA转录及蛋白表达均较正常小鼠显著增加(CTGF mRNA:1.052±0.004和0.402±0.009,P<0.01;CTGF蛋白:3.364±0.460和1.206±0.271,P<0.01);而γ-GCS mRNA表达较健康对照组显著减少(0.952±0.011和1.145±0.066,P<0.01);Pearson回归分析显示MRL/lpr狼疮小鼠肾组织中CTGF mRNA表达量与γ-GCS mRNA表达量量负相关(r=-0.902,P<0.01).结论 MRL/lpr小鼠肾脏中存在γ-GCS表达异常降低,机体抗氧化能力减低,而且与CTGF的表达呈负相关,可能因此而参与了肾脏纤维化的进程.     

广谱基质金属蛋白酶抑制剂对高血压肾纤维化的影响

目的 研究多西环素(DOX)对卒中易感型自发性高血压大鼠(SHR-SP)肾脏基质金属蛋白酶(MMPs)及金属蛋白酶组织型抑制剂(TIMPs)活性的影响,探讨DOX对高血压肾纤维化病理转归的作用机制.方法 选用7周龄雄性SHR-SP随机分为药物干预组和对照组,定期观察大鼠体重、测量无创鼠尾压、尿量、尿肌酐、尿蛋白变化.观察终止时进行血流动力学分析;测定血清肌酐、尿素氮浓度;采用组织病理、明胶酶谱和逆明胶酶谱等方法观察各组大鼠肾脏组织学改变和MMP-2、MMP-9、TIMP-1、TIMP-2等活性变化.结果 收缩压、脉压、血清肌酐浓度在DOX组与对照组之间无统计学差异,但DOX组有升高趋势;从19周龄起,DOX组大鼠尿蛋白浓度与尿肌酐浓度比值即高于对照组[(8.3±6.4 vs 3.3±2.0)mg/μmol,P＜0.05];病理染色显示肾小管损伤平均指数和胶原容积分数均高于对照组(损伤平均指数:3.14±0.47 vs 2.69±0.38,P＜0.05;胶原容积分数:10.5%±2.7% vs 6.6%±1.9%,P＜0.01);与血压正常大鼠相比,高血压大鼠肾脏MMP-2、MMP-9、TIMP-1和TIMP-2的活性升高;药物干预后MMP-2、MMP-9活性降低(MMP-2:2.62±0.75 vs 3.39±0.92;MMP-9:2.89±1.13 vs 4.01±0.91,P＜0.05),而TIMP-1、TIMP-2活性则显著升高(TIMP-1:2.89±1.76 vs 1.54±0.86,P＜0.05;TIMP-2:1.69±0.47 vs 1.06±0.47,P＜0.01).结论 广谱基质金属蛋白酶抑制剂DOX可以抑制SHR-SP肾脏中MMP-2、MMP-9活性,加重高血压造成的肾脏损害.在肾脏损害发生后,抑制MMPs活性可能会加重高血压肾脏纤维化的进展.     

Anti-macrophage-derived chemokine antibody relieves murine lupus nephritis

We observed the distribution of monocyte’s changes in damage to renal tissue and the expression of macrophage-derived chemokine (MDC) in MRL/lpr mice. The 8-week-old MRL/lpr mice were randomly assigned to receive either MDC antibodies (n = 6) or placebo (n = 6) at a once-every-other-day dose of 300 μl from week 4. We then quantified the differences in 24-h urine protein and serum creatinine concentrations, performed a histological evaluation of renal tissue and assessed the expression of MDC protein and mRNA between the two groups 4 weeks after treatment was initiated. Antibody-treated mice demonstrated significantly lower urine protein and serum creatinine concentrations and had fewer renal lesions compared with control mice. The expression of MDC protein and mRNA in renal tissues was significantly lower in the antibody-treated mice than in control mice, suggesting that the elevated expression of MDC, which led to monocyte infiltration in the kidney, may play an important role in the development of lupus nephritis. Furthermore, the anti-MDC antibodies may act to alleviate the renal lesions of murine lupus nephritis by inhibiting the infiltration of monocytes in the renal tissue of the lupus mice.     

Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL/lpr mice

OBJECTIVE: To determine the role of Fc receptors (FcR), which play crucial roles in antibody and immune complex-mediated inflammation and autoimmunity, including glomerulonephritis (GN), in the development of autoimmune GN and vasculitis in MRL/lpr mice, one of the most widely used lupus-prone mouse models. METHODS: FcRgamma(-/-) MRL/lpr mice were generated by backcrossing for 8 generations. The development of GN and vasculitis of various sized vessels was analyzed histopathologically in the kidney, lung, and skin. Autoantibody and immune complex levels were determined biochemically at 16-24 weeks of age and compared with the findings in FcRgamma(+) MRL/lpr mice. The lifespan of the mice was also recorded. RESULTS: Diffuse proliferative GN, with deposition of IgG and C3, developed in both FcRgamma(-/-) and FcRgamma(+) MRL/lpr mice. There was no difference in the survival rate and degree of proteinuria between FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. Regardless of the level of FcR expression, there were no significant differences in the levels of serum IgG, anti-DNA antibody, or circulating immune complexes between the two types of mice. Necrotizing vasculitis in medium-sized arteries of the kidneys and lungs as well as small-vessel vasculitis in the skin was observed in both in FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. In contrast, the Arthus reaction was induced in FcRgamma(+) MRL/lpr mice, but not in FcRgamma(-/-) MRL/lpr mice. CONCLUSION: Unlike (NZB x NZW)F(1), the other strain of lupus-prone mice that develops GN in an FcR-dependent manner, the development of autoimmune GN and vasculitis in MRL/lpr mice was FcR-independent, implying heterogeneity of the contribution of FcR to the development of autoimmune disease.     

Experimental studies on the pathogenesis and development of interstitial pneumonia and pulmonary fibrosis

In order to elucidate the mechanism of pulmonary fibrosis development, analysis of bronchoalveolar lavage fluid (BALF), alveolar macrophage function and histological examination were performed in bleomycin (BLM) treated mice and MRL/lpr mice. In the BLM-treated group, swelling of type II alveolar cells, increase of phospholipids and total cell counts in BALF were observed at the early stage following BLM administration. Lysosomal enzyme activities, total protein volume, superoxide production and IL-1 production of alveolar macrophages peaked at the second week after completing BLM administration. In MRL/lpr mice, lymphocytes infiltration in the interstitium, perivascular and peribronchial granuloma formation were observed at 24 weeks old. Analysis of BALF revealed the increase of total cell counts, lymphocyte counts, and fibronectin volume. No significant difference was observed in total protein and phospholipid volume between MRL/lpr mice and MRL/n mice (control mice).     

A novel treatment for lupus nephritis: lignan precursor derived from flax

BACKGROUND: Flaxseed has renoprotective effects in animal and human lupus nephritis. We have recently extracted the lignan precursor (secoisolariresinol diglucoside) (SDG) to determine if this more palatable derivative of flaxseed would exert renoprotection similar to the whole flaxseed in the aggressive MRL/lpr lupus mouse model. METHODS: 131 MRL/lpr mice were randomly assigned to saline gavage, 600, 1,200 and 4,800 microg lignan gavage groups. At 7 weeks, 6 animals underwent platelet aggregating factor (PAF) lethal challenge and 40 were studied with urine collection to determine the levels of secoisolariresinol, enterodiol and enterolactone in the gavaged animals. A baseline study of 10 saline gavaged animals took place at 6 weeks. 25 animals in the saline gavage, 600 and 1200 microg lignan groups were studied at 14 and 22 weeks for GFR, spleen lymphocyte S-phase and organ weight studies. RESULTS: Metabolic studies indicated that secoisolariresinol is the major metabolite absorbed and the lowest lignan dose provides a lengthening in survival for the PAF lethal challenge. Body weight, fluid and water intake studies demonstrated that the lignan was well tolerated. Changes in proteinuria, GFR and renal size showed a time- and dose-dependent protection for the lignan precursor. Cervical lymph node size and spleen lymphocyte cells in the S-phase demonstrated modest dose-dependent reductions in the lignan gavaged groups. CONCLUSION: SDG was converted in the gut to secoisolariresinol, which was absorbed and well tolerated by the MRL/lpr mice. Renoprotection was evidenced, in a dose-dependent fashion, by a significant delay in the onset of proteinuria with preservation in GFR and renal size. This study suggests that SDG may have a therapeutic role in lupus nephritis.     

Prevention and reversal of nephritis in MRL/lpr mice with a single injection of C-reactive protein

OBJECTIVE: C-reactive protein (CRP) is an acute-phase serum protein with binding reactivity to nuclear autoantigens and immunomodulatory function. The MRL/lpr mouse is an important model of human systemic lupus erythematosus (SLE). These mice develop high-titer anti-DNA antibodies and immune complex-mediated nephritis and exhibit progressive lymphadenopathy. The mortality rate among these mice is 50% by age 18-20 weeks; the most frequent cause of death is glomerulonephritis. The present study was undertaken to determine whether treatment of mice with CRP would affect the course of lupus nephritis. METHODS: MRL/lpr mice were treated with a single 200-mug injection of CRP at either age 6 weeks (before disease onset) or age 13 or 15 weeks (when proteinuria had reached high levels). Proteinuria was measured weekly, and levels of anti-double-stranded DNA autoantibodies and blood urea nitrogen were determined monthly. Glomerular immune complex deposition and renal pathology were assessed in mice ages 15 weeks and 17 weeks. RESULTS: Early CRP treatment markedly delayed the onset of proteinuria and lymphadenopathy, increased survival, and reduced levels of autoantibodies to DNA. Treatment of mice with active disease reversed proteinuria and prolonged survival. Renal disease was decreased in CRP-treated mice, with a marked suppression of glomerular pathology, tubular degeneration, and interstitial inflammation, which correlated with the decrease in proteinuria and azotemia. CONCLUSION: These findings demonstrate that systemic suppression of autoimmunity is initiated by a single injection of CRP. Long-term maintenance of CRP-mediated protection was reversed by injection of an anti-CD25 monoclonal antibody but not by macrophage depletion, suggesting that disease suppression is maintained by CD25-bearing T cells.     

Abrogation of skin disease in LUPUS-prone MRL/FASlpr mice by means of a novel tylophorine analog

OBJECTIVE: To test the therapeutic effect of DCB-3503, a synthetic compound derived from a natural product that inhibits NF-kappaB, on end-organ disease in the MRL-Fas(lpr) murine model of systemic lupus erythematosus (SLE). METHODS: Eight-week-old female MRL/Fas(lpr) mice were treated intraperitoneally with a low (2 mg/kg) or high (6 mg/kg) dose of DCB-3503 for 10 weeks. Control groups were administered vehicle treatment alone (negative control) or 25 mg/kg cyclophosphamide (positive control). Mice were bled before (8 weeks) and during (13 weeks) treatment, and when they were killed (20 weeks), and serum samples were analyzed for total IgM and IgG levels and autoantibody titers. When the mice were killed, spleen and lymph nodes (axillary, brachial, and cervical) were examined by flow cytometric analysis. The presence of skin and renal disease was determined by histopathologic analysis. RESULTS: DCB-3503 reduced anti-double-stranded DNA and antichromatin autoantibodies and nearly abrogated inflammatory skin disease in MRL/Fas(lpr) mice; however, it had little effect on histologic kidney disease. Treated mice did not have hematologic or hepatic toxicity. These data indicate that end-organ disease in MRL/Fas(lpr) mice responds differentially to NF-kappaB inhibitor. CONCLUSION: DCB-3503 causes significant abrogation of skin disease in MRL/Fas(lpr) mice and may potentially be beneficial in the treatment of inflammatory skin disease in SLE.     

Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice

OBJECTIVE: To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice. METHODS: NH(2)-terminal-truncated monocyte chemoattractant protein 1 (MCP-1)/CCL2 or thymus and activation-regulated chemokine (TARC)/CCL17 analogs were inserted into the pCXN2 expression vector and transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1, established from an MRL/gld mouse. RESULTS: MCP-1 antagonist- or TARC antagonist-transfected MRL/N-1 cells were injected subcutaneously into MRL/lpr mice ages 7 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease). After 8 weeks, mice bearing the MCP-1 antagonist showed markedly diminished infiltration of macrophages and T cells, glomerular hypercellularity, glomerulosclerosis, crescent formation, and vasculitis compared with control mice. This seemed to be due to decreased production of interferon-gamma and interleukin-2 in the kidney. In contrast, there was no significant difference in renal damage between mice bearing TARC antagonist and control mice. CONCLUSION: We established a new system using MRL/N-1 cells that allows long-term observation of the effects of chemokine antagonists on lupus nephritis in MRL/lpr mice. We also showed that the MCP-1 antagonist ameliorated the initiation and progression of lupus nephritis and of renal vasculitis, which might provide a new approach to the treatment of the disease.     

Increased expression of insulin-like growth factors in progressive glomerulonephritis of the MRL/lpr mouse

Glomerulonephritis is an important complication of systemic lupus erythematosus (SLE). The tissue distribution and exact role of the insulin-like growth factors (IGFs) in the development of lupus nephritis in the MRL/lpr mouse model have not been established. The present study was undertaken to evaluate the changes over time in mRNA and peptide expression of IGF-I and IGFBP-2 in the MRL/lpr mouse. Using in situ hybridization and immunocytochemistry techniques, the expression of IGF-I and IGFBP-2 in MRL/lpr mouse was examined and compared to their congenic normal MRL-++ mouse counterparts from nine to 24 weeks of age. In the MRL-++ and MRL/lpr mouse kidneys, IGF-I and IGFBP-2 mRNA expression was limited to the cortical and medullary collecting ducts, while their immunoreactivity (IR) was localized to the cortical and medullary collecting ducts, loop of Henle, glomeruli and proximal tubules. Over time, and with progression of disease, the MRL/lpr mice displayed a significant increase in IGF-I IR and a modest increase in IGFBP-2 IR within the outer cortical glomeruli, which was associated with a significant increase in glomerulosclerosis and glomerular cell proliferation and with a significant decrease in renal function. In conclusion, this overexpression of IGF-I and IGFBP-2 within the glomeruli of the MRL/lpr mouse kidney supports their potential role in the alterations in renal function and morphology that accompany lupus nephritis.     

JAK/STAT1信号转导途径在MRL/lpr狼疮鼠不同器官中的活化研究

目的探讨Janus蛋白酪氨酸激酶(JAK)/信号转导和转录激活子1(STAT1)信号转导途径在MRL/lpr狼疮鼠肾脏、肺脏、脑等不同器官中的活化和作用。方法实验组是12周龄以上已经发病的MRL/lpr雌性小鼠．对照组是未发病的同龄MRL/lpr雌性小鼠。采用免疫组织化学方法研究肾脏中磷酸化STAT1的组织分布情况。采用Western blot方法研究STAT1磷酸化蛋白表达,采用SYBR greenⅠre- M-time定量聚合酶链反应(PCR)研究SOCS-1 mRNA的表达；并与肺脏、脑相对比。结果MRL/lpr狼疮鼠STAT1磷酸化蛋白在各器官均明显活化。肾脏和肺脏的STAT1磷酸化蛋白活化较脑组织明显；肾脏、肺脏和脑组织的SOCS-1基因的表达均升高．但肾脏的SOCS-1基因表达升高程度低于肺脏和脑组织。结论JAK/STAT1信号转导途径的异常可能参与和促进了系统性红斑狼疮(SLE)各器官病理损害的发生；狼疮肾炎的病理损害还可能与SOCS-1的负反馈调节作用降低有关。