血清巨噬细胞移动抑制因子水平与SLE活动性的关系

目的:观察SLE患者血清巨噬细胞移动抑制因子(macrophage migration inhibitory factor,MIF)水平的变化,并探讨其与SLE疾病活动性、血清免疫学指标的相关关系.方法:用酶联免疫吸附法测定34例活动期和21例静止期SLE患者的血清MIF浓度,并以18名正常人作对照,观察SLE患者血清MIF的改变及其与疾病活动性、血清免疫学指标的相关关系.结果:SLE患者血清MIF水平较正常人显著升高(P＜0.01),活动期比静止期显著升高(P＜0.01).血清MIF水平与SLE疾病活动指数(SLE dis-ease activity index,SLEDAI)、双链DNA(double stranded DNA,ds-DNA)抗体、IgG水平呈显著正相关(r=0.763,P＜0.01,r=0.64,P＜0.01,r=0.48,P＜0.01);与血清补体C3、G4呈负相关(r=-0.57,P＜0.01;r=-0.39,P＜0.05);与抗核抗体无相关(r=0.16,P＞0.05).结论:血清MIF浓度可作为SLE疾病活动的重要指标之一.     

脓毒症小鼠心和肾组织中巨噬细胞移动抑制因子的表达

目的 探讨巨噬细胞移动抑制因子(MIF)在脓毒症小鼠心脏和肾组织中的表达规律.方法采用盲肠结扎穿孔术(CLP)建立脓毒症BALB/c小鼠模型.30只小鼠随机分为5组,分别为假手术组,CLP后12、24、36、48 h组,其中假手术组小鼠在假手术后24 h取标本检测作为对照组,其余四组小鼠分别在CLP术后的12 h、24 h、36 h和48 h取标本待检.采用逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法(Western Blotting)检测脓毒症小鼠心脏和肾组织中NIF的mRNA和蛋白表达.采用单因素方差分析(one-way AN0vA)方法进行计量资料的统计分析.结果 与对照组比较,MIF在脓毒症小鼠心脏组织中的表达增加,在CLP术后12 h开始升高(P<0.05),36 h达峰值(P<0.01),48h仍维持较高水平(P<0.05);肾组织中MIF mRNA的表达在CIP术后12 h开始增加(P<0.05),24h达峰值(P<0.01),48 h后才开始减少,MIF蛋白则只在CLP术后24 h和36 h增加明显(P<0.05).结论脓毒症发生后的12 h～48 h,MIF在脓毒症小鼠心脏和肾组织中的表达有不同程度增加,表达时相基本一致,提示N1F可作为晚期细胞因子参与小鼠脓毒症的发病.     

巨噬细胞移动抑制因子在急性胰腺炎中的表达与CT分级的对比研究

目的 研究急性胰腺炎(AP)患者血浆巨噬细胞移动抑制因子(MIF)含量的表达及相应的CT表现,并分析其临床意义.方法 按照Bahhazar分级将58例急性胰腺炎CT图像改变分为A、B、C、D和E共5个级别,各级别分别与相应的MIF含量相比较分析.结果 A、B级(水肿型)时血浆MIF含量较对照组明显升高,差异有统计学意义(P<0.05);C、D、E级(出血坏死型)时MIF水平较对照组和急性水肿型胰腺炎组升高,差异有统计学意义(P均<0.05).且Balthazar CT分级评分与M1F水平呈正相关(r=0.637,P<0.05).结论 MIF在急性胰腺炎的发生、发展中起着重要作用,动态检测AP患者血浆中MIF含量有助于预测患者病情及指导临床诊断和治疗.     

2型糖尿病肾病患者巨噬细胞移动抑制因子及尿微量白蛋白的表达及其意义

目的:通过检测2型糖尿病肾病患者尿微量白蛋白 (mA1b)及巨噬细胞移动抑制因子(MIF),了解MIF及mA1b在2型糖尿病肾病患者中的变化.方法:将138例患者按WHO诊断标准分型,分为2型糖尿病肾病合并冠心病患者及2型糖尿病肾病但无明确冠心病依据的患者,采用ELISA法和免疫比浊法观察比较两组2型糖尿病肾病患者MIF及mA1b含量.结果:2型糖尿病肾病合并冠心病组患者MIF水平(32.61 ± 5.1)μg/L及mA1b水平(63.00 ± 15.2)mg/L高于无明确冠心病的患者MIF(14.32 ± 3.20)μg/L及mA1b(21.00 ± 10.00)mg/L,差异有统计学意义(均P ＜ 0.05),两组患者MIF及mA1b水平又均显著高于对照组MIF(6.37 ± 1.2)μg/L及mA1b(13.75 ± 5.75)mg/L.结论:检测糖尿病肾病患者 MIF 及mA1b,可作为诊断糖尿病肾病患者早期肾损害的参考指标.     

成人斯蒂尔病诊断与治疗

成人斯蒂尔病（AOSD）是一种自身免疫性风湿病，临床上以发热、关节痛、皮疹、白细胞增高为主要特征，实验室检查主要显示非特异性的炎症反应。非甾体抗炎药联合激素治疗AOSD取得了较好的疗效。本文就AOSD的诊断和治疗进行阐述。     

巨噬细胞移动抑制因子、血管生成素-2、血管内皮生长因子在子宫内膜异位症中的意义

目的观察巨噬细胞移动抑制因子(MMIF)、血管生成素-2(Ang-2)、血管内皮生长因子(VEGF)在子宫内膜异位症(EMs)检测中的临床意义。方法选取2011年1月至2014年6月经病理确诊的EMs患者98例,为异位内膜组。按照美国生殖协会分期标准(R-AFS)分期分为Ⅰ期26例、Ⅱ期29例、Ⅲ期22例和Ⅳ期21例;按照痛经评分0~1分57例和2~3分42例。选择同期确诊的良性肿瘤患者30例为在位内膜组。同时选择同期体检的健康妇女30例,为健康对照组。观察各组血清MMIF、VEGF和Ang-2水平,以及MMIF、VEGF和Ang-2水平与EMs分期和痛经评分的关系。结果异位内膜组和在位内膜组的MMIF、VEGF和Ang-2水平明显高于正常对照组(P0.01),而异位内膜组的MMIF、VEGF和Ang-2水平明显高于在位内膜组(P0.01)。EMs患者的MMIF、VEGF和Ang-2水平随着r-AFS分期级别和痛经评分的升高而升高(P0.05或P0.01)。结论 MMIF、VEGF和Ang-2参与了EMs的发生和发展,有望成为EMs诊断和靶向治疗提供新的思路。     

原发性肝细胞癌患者血清巨噬细胞移动抑制因子水平与血管内皮生长因子和临床病理的关系

化呈正相关(r=0.412,P<0.01).结论 血清MIF升高与VEGF升高相关,MIF和VEGF在HCC发展进程中可能促进肿瘤的生长和转移.     

巨噬细胞移动抑制因子在2型糖尿病合并冠心病中的作用研究

目的探讨巨噬细胞移动抑制因子(MIF)水平与2型糖尿病(T2DM)合并冠心病(CHD)的关系及其临床意义。方法选取T2DM合并CHD(T2DM+CHD组)患者46例、单纯T2DM(T2DM组)患者45例、单纯CHD(CHD组)患者44例、门诊体检者(对照组)45例,检测各组血清MIF水平、空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)浓度、糖化血红蛋白(HbA1c)和空腹血清胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)、体重指数(BMI),并作相关分析。结果 T2DM+CHD组血清MIF水平均明显高于T2DM组、CHD组和对照组,差异均有统计学意义(q分别=2.58、2.33、2.87,P均<0.05)。T2DM+CHD组和T2DM组MIF水平均与TG、HbA1c呈正相关(r分别=0.35、0.26、0.29、0.31,P均<0.05);T2DM与MIF、HbA1c密切相关(OR分别=2.11、1.09,P均<0.05),T2DM合并CHD与MIF、TG密切相关(OR分别=3.95、2.29,P均<0.05)。结论血清MIF与T2DM合并CHD的发病有一定联系。     

类风湿关节炎滑膜中巨噬细胞移动抑制因子的表达及意义

目的探索巨噬细胞移动抑制因子（MIF）在类风湿性关节炎中的作用。方法建立类风湿关节炎小鼠模型,分为生理盐水对照组、空载体对照组和MIF—siRNA转染组,各15只,分别予以处理;通过RT—PCR检测关节膜组织中MIF的表达情况;关节膜组织中的MIF、磷脂酶A2（PLA2）、环氧化酶2（COX2）、血管内皮生长因子（VEGF）等表达通过WesternBlot检测。结果MIF—siRNA能有效地降低关节膜组织中的MIF的表达,关节膜内的MIF、PLA2、COX2、VEGF均表达下降。结论MIF—siRNA在类风湿性关节炎模型中能关闭细胞的MIF基因,有效阻断MIFmRNA和蛋白的表达,随之而来的是PLA2、COX2、VEGF的表达下调。     

特应性皮炎患者外周血单个核细胞、血清及泪液中MIF检测的临床意义

目的 探讨MIF在AD患者PBMC、血清及泪液中的表达水平及其在AD诊断中的临床意义.方法 AD患者按SCORAD指数分3个亚组,轻度AD组11例、中度AD组23例、重度AD组9例;并用实时定量RT-PCR检测43例AD患者和31名健康对照者(健康对照组)PBMC中MIFmRNA的表达水平,用ELISA法检测血清和泪液中MIF含量.结果 AD组PBMC中MIF mRNA的表达水平为7.46(3.38～8.90),明显高于健康对照组[1.67(1.24～2.45),Z=-6.141,P<0.05];轻、中、重度AD组MIF mRNA的表达水平分别为2.35(2.12～2.49)、7.83(6.54～8.90)和8.76(8.22～9.73),中、重度AD组均显著高于健康对照组(Z值分别为-6.237、-4.520,P均<0.05).AD组血清中MIF的含量为36.32(11.89～43.80)μg/L,明显高于健康对照组[7.89(6.13～9.54)μg/L,Z=-6.180,P<0.05];轻、中、重度AD组血清中MIF的含量分别为8.98(7.90～10.51)μg/L、36.50(29.78～43.23)μg/L、45.70(41.27～48.84)μg/L,中、重度AD组均显著高于健康对照组(Z值分别为-6.238、-4.521,P均<0.05).AD组泪液中MIF的含量为12.66(2.01～20.12)μg/L,较健康对照组[0.85(0.77～1.06)μg/L]明显升高(Z=-4.118,P<0.05);轻、中、重度AD组泪液中MIF的含量分别为1.10(0.83～1.35)μg/L、12.66(9.76～15.87)μg/L、24.65(19.29～30.94)μg/L,中、重度AD组均显著高于健康对照组(Z值分别为-4.062、-3.372,P均<0.05).中、重度AD组PBMC中MIF mRNA表达水平及血清、泪液中MIF的含量与疾病严重程度SCORAD指数均呈明显正相关(r值分别为0.395、0.404、0.515,P均<0.05).结论 不同AD病程患者PBMC、血清和泪液中MIF表达增高,MIF可作为判断AD病情活动和评价AD疾病严重程度的有效检验指标.     

巨噬细胞移动抑制因子在脓毒症小鼠中的作用及其干预研究

目的 观察巨噬细胞移动抑制因子(MIF)在脓毒症小鼠血清和肺组织中的表达及MIF拮抗剂ISO-1对脓毒症小鼠存活率的影响.方法 用盲肠结扎穿孔术(CLP)建立脓毒症BALB/c小鼠模型.40只小鼠随机分为假手术组及CLP后12、24、36、48 h组,各取8只小鼠心脏血,采用酶联免疫吸附法(ELISA)检测血清MIF水平,采用逆转录-聚合酶链反应(RT-PCR)、蛋白质免迹印迹法(Western blotting)检测肺组织中MIF的mRNA和蛋白表达.另选择40只小鼠制备脓毒症模型,观察用ISO-1干预后脓毒症小鼠10 d的存活率.结果 与假手术组比较,脓毒症小鼠血清MIF水平逐渐升高,36 h达峰值,48 h有所下降,但仍高于假手术组(P均<0.01);肺组织MIF mRNA和蛋白表达自12 h起即明显增加,之后逐渐增加至48 h达峰值(P<0.05或P<0.01).使用MIF拮抗剂ISO-1的脓毒症组小鼠10 d存活率为60%(12/20),较脓毒症对照组25%(5/20)明显升高(P<0.05).结论 MIF可能作为晚期炎症细胞因子参与脓毒症小鼠的发病过程,使用MIF拮抗剂ISO-1能提高脓毒症小鼠的存活率,提示MIF可作为脓毒症治疗的靶向.     

RNA干扰巨噬细胞移动抑制因子对宫颈癌Caski细胞上皮-间质转化的影响

目的通过RNA干扰技术研究巨噬细胞移动抑制因子(MIF)对宫颈癌Caski细胞上皮-间质转化(EMT)的影响作用。方法通过构建重组真核表达载体p Genesil-1-MIF si RNA,转染宫颈癌Caski细胞(Caski-p Genesil-MIF si RNA组),同时设空载体转染组(Caski-p Genesil-1组)和空白对照组(Caski组),采用荧光定量聚合酶链反应(PCR)和蛋白质印迹法(Western blot)检测Caski细胞中MIF m RNA相对表达量的变化,并检测转染前后Caski细胞中EMT相关指标E-cadherin和Vimentin的表达变化。结果 p Genesil-1-MIF si RNA转染Caski细胞后MIF m RNA的表达量减少,低于对照组,差异有统计学意义(P<0.05);RNA干扰抑制MIF基因表达后,与对照组相比,p Genesil-1-MIF si RNA组Caski细胞上皮标记物E-cadherin m RNA及蛋白表达水平上调(P<0.05),间叶标记物Vimentin m RNA及蛋白表达水平显著下调(P<0.05)。结论抑制MIF基因表达可抑制宫颈癌Caski细胞发生EMT的能力。     

老年冠心病患者胱抑素 C、巨噬细胞移动抑制因子及基质金属蛋白酶-1在血清中的表达分析

目的：探讨老年冠心病患者血清胱抑素 C、巨噬细胞移动抑制因子(MIF)、基质金属蛋白酶-1(MMP-1)在不同病变程度中的表达差异。方法选取心血管内科2012年7月至2014年8月收治的老年冠心病患者120例,根据冠状动脉造影结果并结合心电图、心肌酶谱等检查将其分为对照组(30例)、稳定型心绞痛组(SAP 组,34例)、不稳定型心绞痛组(UA 组,28例)、急性心肌梗死组(AMI 组,28例)。比较4组患者血清胱抑素 C、MIF、MMP-1及高敏 C 反应蛋白(hs-CRP)水平,并进行4项指标间的相关性分析。结果4组患者血清胱抑素 C、MIF、MMP-1及 hs-CRP 水平比较差异均有统计学意义(P <0.05);血清胱抑素C、MIF、MMP-1水平均随病情进展逐渐增加,且组间两两比较差异均有统计学意义(P <0.05);AMI 组患者血清 hs-CRP 水平与其余3组比较差异均有统计学意义(P <0.05);对照组、SPA 组和 UA 组患者血清 hs-CRP 水平两两比较差异均无统计学意义(P >0.05)。胱抑素 C、MIF、MMP-1三者间呈明显正相关。结论冠心病患者血清胱抑素 C、MIF 和 MMP-1水平,随着病情的加重有逐渐升高的趋势,可作为病情评估的重要指标。     

Comparative levels of macrophage migration inhibitory factor, procalcitonin, osteoprotegerin, interleukin-8, hs-C reactive protein, d-dimer in febrile neutropenia, newly diagnosed cancer patients, and infectious fever

Background

The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and d-dimer during fever above 38.3 °C due to various causes.

Material and methods

Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and d-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection.

Results

IL-8 and d-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs-CRP values.

Conclusion

High serum IL-8 and d-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer.     

类风湿性关节炎关节液中巨噬细胞移动抑制因子与血管内皮生长因子及磷脂酶A2关系研究

目的探讨类风湿性关节炎患者（rheumatoid arthritis,RA）关节液中巨噬细胞移动抑制因子（macrophage migration inhibitory factor,MIF）与血管内皮生长因子（vascular endothelial growth factor,VEGF）、磷脂酶A2（phospholipase A2,PLA2）的关系。方法 RA患者30例为RA组,体检健康者30例为对照组,2组采用ELISA法检测患者关节液中MIF、VEGF及PLA2水平,采用RT-PCR检测关节液中MIF、VEGF及PLA2基因表达情况。结果 RA组MIF、VEGF和PLA2水平明显高于对照组（P〈0.05）;RA组MIF、VEGF、PLA2表达水平在晨僵时间、关节肿胀个数及有无手X线异常改变上差异有统计学意义（P〈0.05）,在有无皮下结节、类风湿因子及血沉水平比较差异无统计学意义（P〉0.05）;RA组MIF高表达者关节液VEGF、PLA2基因表达较MIF低表达者明显增高（P〈0.05）。结论 RA患者关节液中MIF水平明显增高,并与VEGF、PLA2表达密切相关。     

蛋白激酶Cβ抑制剂LY333531对阿霉素肾病小鼠肾脏的保护作用

目的:探讨蛋白激酶Cβ抑制剂LY333531对阿霉素肾病小鼠肾脏的保护作用。方法:24只雄性、8周龄BALB/c小鼠随机分为肾病组、治疗组和对照组(n=8),肾病组和治疗组一次性尾静脉注射阿霉素(10mg/kg),对照组注射等量生理盐水;阿霉素注射后第5天,治疗组予LY33353110mg/(kg·d)灌胃,肾病组和对照组予等量溶媒灌胃。阿霉素注射后2周处死小鼠。处死前留取尿标本检测尿蛋白和肌酐。观察肾脏病理、巨噬细胞浸润、巨噬细胞移动抑制因子(MIF)和单核细胞趋化蛋白-1(MCP-1)的表达。结果:与对照组相比,肾病组尿蛋白肌酐比值升高,肾脏巨噬细胞浸润、MCP-1和MIF表达增加(P<0.01);与肾病组相比,治疗组尿蛋白/肌酐比值下降,肾脏巨噬细胞浸润、MCP-1和MIF表达减少(P<0.01)。结论:LY333531对阿霉素肾病小鼠肾脏具有保护作用,其机制可能与下调阿霉素肾病小鼠肾脏MCP-1和MIF表达,抑制巨噬细胞浸润有关。     

Atypical adult-onset Still’s disease with an initial and sole manifestation of liver injury: A case report and review of literature

BACKGROUNDAdult-onset Still''s disease (AOSD) typically presents with a high spiking fever, polyarthritis, transient maculopapular rash, neutrophilic leukocytosis, and hepatosplenomegaly. It has a wide spectrum of clinical symptoms ranging from mild to severe, with extensive involvement of almost every organ. Although liver involvement in the form of increased hepatic enzymes and bilirubin is common, no AOSD case with liver involvement as the initial manifestation of AOSD has been reported. CASE SUMMARYA 35-year-old woman presented to the hepatology department with progressively worsening jaundice for one week. Liver chemistry tests revealed a significantly increased liver enzymes and bilirubin level. Given that the clinical examination was unremarkable, liver biopsy was considered because the patient had a history of AOSD 6 years ago. Liver histopathology revealed that most hepatic lobules were still recognizable. Fusional necrosis was observed around most central veins. A few bridging necrotic zones were also found. Infiltration of multiple plasma cells were observed in the necrotic zone, and the reticular scaffold was still expanded. Additionally, no obvious fibrosis was observed in the portal area. Mild mixed inflammatory cell infiltration was noted in the interstitium of the portal area. Further examination was unremarkable except for a remarkably high level of ferritin. Collectively, a presumptive diagnosis of liver injury secondary to AOSD was made. The hepatic involvement responded well to glucocorticoid treatment.CONCLUSIONThis case highlights that hepatic involvement as an initial and sole manifestation could be a pattern of relapsed AOSD. The diagnosis of AOSD should be considered in the case of nonresolving liver injury after the exclusion of common etiologies for liver diseases. A liver biopsy can be useful for the differential diagnosis of liver injury associated with AOSD.     

Macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis: clinical implications and pathogenic significance

BACKGROUND: Inflammatory cytokines produced by activated macrophages are implicated in the pathogenesis of ulcerative colitis (UC). With the theory that macrophage migration inhibitory factor (MIF) may have a role in the accumulation of macrophages, we studied MIF in UC. MATERIALS AND METHODS: A total of 27 patients with UC, 14 patients with Crohn's diseases (CD), 11 patients with other forms of colitis and 26 normal controls were enrolled in the study. The levels of MIF in the sera and culture supernatant were measured by an enzyme-linked immunosorbent assay. MIF, macrophages and T cells were localized at the colonic mucosa by immunohistochemistry. RESULTS: The levels of MIF in the sera were significantly higher in UC than in normal controls (P < 0.05), in serum C-reactive protein (CRP) -positive cases with UC than in CRP-negative cases with UC (P < 0.05), and in patients with severe colitis with UC than in mild colitis with UC (P < 0.05). There was a positive relationship between serum MIF levels with the CRP levels and activities of colitis. However, the levels of MIF in patients with CD and other forms of colitis were not significantly different from their levels in normal controls and UC. Infiltrating cells at the colonic mucosa in UC and CD expressed MIF. CONCLUSIONS: These data suggest a role of MIF in the pathogenesis of UC. MIF may be used as a marker of disease activity in UC and control of MIF production may have therapeutic implications.     

胃癌患者血清巨噬细胞移动抑制因子水平的临床意义

目的：检测胃癌患者血清巨噬细胞移动抑制因子（MIF）的浓度水平,并评估其在胃癌诊断中的应用价值。方法用ELISA方法检测2007年2月至2010年4月在我院手术胃癌患者106例,其中男71例,女35例,平均年龄56.2岁（22～78岁）。所有病例均经病理学确认为原发性胃癌）、48例胃炎患者（接受胃镜检查诊断为慢性胃炎）及50例健康（健康体检者,排除一切肿瘤以及炎症性相关疾病）对照者血清MIF水平,同时测定癌胚抗原CEA。通过多因素Logistic回归分析,利用受试者工作特征（ROC）曲线分析MIF、CEA以及联合诊断对胃癌的诊断价值。结果胃癌患者血清中MIF平均浓度为4586 pg/ml,均高于单纯胃炎患者（1602.4 pg/ml）和健康对照（1105.6 pg/ml）,差异均有显著统计学意义（P均＜0.05）。胃癌患者血清MIF的水平与患者性别、年龄、病理类型不相关。但胃癌患者血清MIF水平随着肿瘤分期的升高而升高,差异有显著统计学意义（P＜0.05）。伴有淋巴结转移胃癌患者MIF水平显著高于未转移者（P＜0.05）。根据ROC曲线分析,MIF检测胃癌的临界值为3018 pg/ml时诊断效能最大,敏感度为79.4%,特异度为85.1%。MIF与CEA联合检测诊断价值高于单独诊断（P＜0.05）。结论胃癌患者血清中存在高水平的MIF,MIF可能为胃癌潜在的肿瘤标志物,MIF联合CEA可提高胃癌的诊断率,值得临床应用。