尿巨噬细胞趋化蛋白-1和巨噬细胞集落刺激因子对狼疮肾炎复发的诊断作用

目的探讨在成功的泼尼松和环磷酰胺诱导治疗后,引起弥漫增生型(Ⅳ型)狼疮肾炎复发的预测指标。方法收集弥漫增生型狼疮肾炎病例,将泼尼松和环磷酰胺诱导治疗成功的病例纳入研究对象。记录临床和实验室资料,于治疗开始后6个月时检测患者尿巨噬细胞趋化蛋白(MCP)-1和巨噬细胞集落刺激因子(M-CSF)。追踪治疗后的复发情况。结果共收集到64例诱导治疗成功的病例,经平均(27±3)个月随访,18例(28%)患者发生至少一次肾性复发,其复发的平均时间为(14±4)个月。复发组患者尿MCP-1和M-CSF水平明显高于缓解维持组。尿MCP-1和M-CSF升高,及血C3降低和抗dsDNA抗体阳性均是Ⅳ型狼疮肾炎复发的独立预测因子。有7例患者出现血肌酐倍增(CRX2),肾性复发是CRX2的惟一预测因子。结论尿MCP-1和M-CSF持续升高是Ⅳ型狼疮肾炎复发的独立预测因子。该研究提示监测诱导缓解患者肾组织炎症指标可有利于指导狼疮肾炎的治疗。     

PNS外周血单核细胞趋化因子与RANTES mRNA的表达及意义

目的 探讨原发性肾病综合征(PNS)患者外周血单核细胞趋化因子(MCP-1)与受激活调节的正常T细胞表达和分泌因子(RANTES)mRNA的表达及临床价值。方法 PNS患者54例，分别于治疗前及治疗后3个月采用逆转录聚合酶链反应(RT—PCR)方法检测外周血MCP-1及RANTES mRNA的表达水平。结果 PNS患者外周血MCP-1、RANTES mRNA的表达显著高于正常对照组。治疗后显著降低；其中膜性肾病患者表达水平较低，系膜毛细血管性肾炎患者表达水平较高；伴有肾小管间质损害者表达水平显著高于无肾小管间质病变者，治疗后未完全缓解者显著高于完全缓解署。MCP-1、RANTES mRNA表达水平与血肌酐水平呈显著正相关，与24小时尿蛋白定量、血清白蛋白水平无显著相关性。结论 PNS患者外周血MCP-1、RANTES mRNA表达水平与病理类型、肾小管间质损害、血清肌酐水平及疗效有一定关联，对其检测有助于PNS病情及预后的评估。     

Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis

Abstract

This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-α (TNF-α) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-α were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-α induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-α may induce granzyme B and RANTES production in RA patients.     

Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis

This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-α (TNF-α) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-α were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-α induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-α may induce granzyme B and RANTES production in RA patients.     

Granulocytic colony-stimulating factors in the management of patients with acute myeloid leukemia

In the early stages of the development of granulocytic colony-stimulating factors (G-CSF and GM-CSF) in oncology and hematology, myeloid malignancies were considered to be a contraindication to their use. In fact, myeloid leukemic cells bear specific receptors for G-CSF and GM-CSF and these CSFs induce an in vitro proliferation in primary blast cells of most patients with acute myeloid leukemia (AML). In addition, autocrine or paracrine loops of stimulation have been demonstrated in some cases. Despite these theoretical risks of blast proliferation, G-CSF and GM-CSF have been extensively tested in patients with AML or myelodysplastic syndromes. Major objectives were the correction of acquired or chemotherapy-induced neutropenia, but also the reinforcement of the antileukemic efficacy of cytotoxic agents. Recently, G-CSF has also been used to mobilize hematopoietic progenitors in the peripheral blood. Major results of several double-blind clinical trials are the demonstration of the safety of CSF administration in these patients, since no risk of in vivo blast cell regrowth has been observed, and their efficacy to shorten the duration of chemotherapy-induced neutropenia. However, no significant reduction in the treatment-related mortality and no survival improvement were afforded by the use of these CSFs. From another point of view, the search for AML-specific CSF-receptor or CSF-receptor associated molecule abnormalities represents a new promising area to try to understand the mechanisms of leukemogenesis.     

急性心肌梗死患者炎症因子C反应蛋白对单核细胞趋化蛋白-1表达的影响

目的探讨急性心肌梗死患者炎症因子C反应蛋白(CRP)与黏附分子单核细胞趋化蛋白-1(MCP-1)表达的关系。方法检测20例急性心肌梗死患者(均选白2007年2～7月在北京医院心内科心脏监护室住院的患者)及27例健康对照者血清生化指标、超敏C反应蛋白(Hs-CRP)及MCP-1水平,分析Hs-CRP与MCP-1的相关性。体外分离培养外周血单核细胞,以不同浓度CRP刺激单核细胞,用定量PCR测定MCP-1表达变化。结果与对照组比较,急性心肌梗死组血清Hs-CRP及MCP-1水平明显升高。急性心肌梗死组与健康对照组Hs-CRP水平分别为:(82.84±43.79)nmol/L和(2.09±5.31)nmol/L(P<0.01);急性心肌梗死组与健康对照组MCP-1水平分别为:(19.61±10.59)nmol/L和(10.78±5.10)nmol/L(P<0.05),且两者呈正相关(r=0.451,P<0.05)。CRP浓度依赖性地增加外周血单核细胞中MCP-1的表达。在CRP水平为47.0～188.0 nmol/L时差异具有统计学意义(P<0.05或P<0.01)。在47.0、94.0、188.0 nmol/L浓度刺激组中MCP-1相对表达量较未刺激组高44%、124%、142%。结论急性心肌梗死患者中,黏附分子MCP-1表达水平升高可能是由于炎症因子CRP增加导致。     

复方牛胎肝提取物减轻非酒精性脂肪性肝炎大鼠肝脏脂肪变性及炎症程度

非酒精性脂肪性肝病(NAFLD)包括单纯性脂肪肝、脂肪性肝炎(NASH)和肝硬化,NASH是NAFLD进展的关键过程;目前尚无满意治疗药物[1].复方牛胎肝提取物主要成分为胰岛素样生长因子([GF)-I、肝细胞生长因子(HGF)等.     

粒-巨噬细胞集落刺激因子在肺泡蛋白沉积症患者中的表达

目的 研究粒－巨噬细胞集落刺激因子（GM－CSF）蛋白及mRNA在4例肺泡蛋白沉积症（PAP）患者中的表达,探索PAP的发病机制。方法 采用ELISA法测定GM－CSF蛋白,采用RT－PCR检测外周血单个核细胞及肺泡巨噬细胞中GM－CSFmRNA表达水平。GM－CSFcDNA测序采用双脱氧链终止反应法。结果 4例PAP中3例外周血单个核细胞和肺泡巨噬细胞均检测不到GM－CSF释放,但mRNA表达水平均正常。cDNA测序发现1例PAP患者GM－CSFcDNA第382位碱基发生点突变（T→C）,致117位氨基酸序列发生改变（异亮氨酸→苏氨酸）。结论 GM－CSF蛋白表达异常与PAP发病可能有关,GM－CSFcDNA点突变可能是导致GM－CSF蛋白表达异常的原因之一。     

粒-巨噬细胞集落刺激因子及肺表面活性蛋白在肺泡蛋白沉积症患者肺内的表达

目的通过观察成人特发性肺泡蛋白沉积症(PAP)患者肺部粒-巨噬细胞集落刺激因子(GM-CSF)及其受体蛋白以及肺泡表面活性蛋白的表达,探讨PAP的发病机制。方法用SP免疫组化技术检测6例PAP患者(PAP组)及6例对照者(对照组)肺组织肺泡巨噬细胞及Ⅱ型肺泡上皮细胞GM-CSF、GM-CSF/IL-3/IL-5共同β链受体(GM-CSFβcR)、肺表面活性蛋白(SP)-A和SP-D蛋白表达。结果(1)肺泡巨噬细胞2组表达GM-CSF蛋白均较弱,阳性细胞数少,组间比较差异无统计学意义(P=0.818);2组均表达GM-CSFβcR蛋白,对照组显著高于PAP组(P=0.002);2组均表达SP-A蛋白,且PAP组呈阳性反应,但阳性细胞数少,积分指数显著低于对照组(P=0.004);2组表达SP-D蛋白差异无统计学意义(P=0.24)。(2)Ⅱ型肺泡上皮细胞2组均表达SP-A和SP-D蛋白,组间比较差异无统计学意义(P=0.818,P=0.485);对照组少数表达GM-CSFβcR蛋白,PAP组无GM-CSFβcR蛋白表达;2组均无GM-CSF蛋白表达。结论肺泡巨噬细胞表达GM-CSFβcR蛋白减少可能与成人特发性PAP肺泡巨噬细胞功能障碍有关。     

Seroprevalence of chikungunya virus infection in five hospitals within Anyigba,Kogi State of Nigeria

Febrile illnesses in developing countries are often misdiagnosed as malaria or typhoid fever. Although arboviral infections have similar clinical symptoms, they are usually not screened because of limited resources and the fact that there are several viruses in this group. Chikungunya virus (CHIKV) has been isolated in parts of Nigeria, but there is no documented evidence of the infection in Kogi State. This study determined seroprevalence of active and past CHIKV infection among febrile patients who tested negative for malaria and typhoid fever. Sera from 243 febrile patients were screened for CHIKV IgG and IgM using an immunochromatographic test kit. Clinical and socio-demographic variables were collected using a structured questionnaire. Recent CHIKV infection was observed in 5.8% of the study participants while 25.1% had IgG antibodies demonstrating previous infection. Significant associations were observed between seropositivity and age of participants (p < 0.001), sex (p = 0.044), marital status (p = 0.002), and occupation (p < 0.001). Clinical symptoms such as fever, joint pain, and headache were significantly associated with seropositivity. This study identified recent CHIKV infection in Anyigba. Therefore, there is need for routine screening of febrile patients and molecular characterization to determine the nature of circulating strains.     

粒细胞-巨噬细胞集落刺激因子编码基因对乙型脑炎DNA疫苗细胞免疫增强效应的影响

目的 研究粒细胞-巨噬细胞集落刺激因子(GM-CSF)编码基因对乙型脑炎(JE)DNA疫苗细胞免疫应答的影响.方法 套式RT-PCR法获取BALB/c小鼠GM-CSF编码基因,构建含乙型脑炎病毒(JEV)前膜(prM)-包膜(E)蛋白与GM-CSF编码基因以及单纯GM-CSF编码基因的重组质粒,分别命名为pJME/GM-CSF和pGM-CSF.脂质体法转染上述质粒入中华仓鼠卵巢细胞(CHO),免疫荧光法检测编码蛋白的表达与分布.流式细胞仪检测经不同组合的免疫原免疫后小鼠脾T淋巴细胞亚群及Th细胞内细胞因子(IFN-γ、IL-4)变化,LDH法测定CTL活性.数据行单因素方差分析及最小显著差数法比较.结果 重组质粒pJME/GM-CSF与pGM-CSF经鉴定构建正确,所编码的蛋白主要分布于胞质,少量分布于胞膜.pJME/GM-CSF组CD4+T淋巴细胞比例为(33.90±0.79)%,明显高于其他组(t值分别为9.818、6.804、6.594、10.061、9.380和17.675,均P<0.05).pJME+pGM-CSF同时注射组及pGM-CSF注射3 d后接种pJME组CD4+T淋巴细胞比例分别为(29.83±0.61)%、(29.70±0.51)%,高于pJME注射3 d后接种pGM-CSF组的(27.69±0.50)%(t=3.466、t=3.255,P<0.05).pJME/GM-CSF组与pJME+pGM-CSF同时注射组CD8+T淋巴细胞比例较空载体(pcDNA3.1+)组及JE灭活疫苗组升高(t值分别为3.811、2.627、10.537和3.811,均P<0.05).pJME/GM-CSF组CTL活性为(51.48±0.10)%,明显高于其他组(t值分别为22.868、13.823、5.377、32.287、34.632和53.795,均P<0.05).pJME/GM-CSF组、pJME+pGM-CSF同时注射组及pGM-CSF注射3 d后接种pJME组IFN-γ/IL-4比值分别为19.13±1.36、12.32±0.82、7.05±0.43,明显高于其他组(P<0.05).结论 GM-CSF编码基因可增强JE DNA疫苗的细胞免疫应答效应.     

基孔肯雅病毒小鼠感染模型研究进展

基孔肯雅病毒(Chikungunya virus, CHIKV)感染引发的基孔肯雅热是一种主要经伊蚊叮咬而传播的虫媒传染病,近些年已在100多个国家流行或暴发,成为严重威胁全球公共卫生安全的虫媒病毒性传染病。CHIKV感染后可以引起急性发热、皮疹、肌肉疼痛以及慢性关节炎、腱鞘炎等临床症状,严重者可发生病毒性脑炎。小鼠模型作为CHIKV最常用的动物感染模型,在病毒感染机理、宿主抗感染免疫机制以及相关疫苗或药物研发等方面应用广泛。本文拟就国内外关于基孔肯雅病毒小鼠感染模型的最新研究进展作一综述。     

Aqueous levels of macrophage migration inhibitory factor and monocyte chemotactic protein-1 in patients with diabetic retinopathy.

AIMS: To investigate the relationship of aqueous macrophage migration inhibitory factor (MIF) and monocyte chemotactic protein-1 (MCP-1) levels with the clinical stage of diabetic retinopathy. METHODS: We assayed MIF and MCP-1 levels in aqueous humour samples obtained from 40 diabetic patients (49 eyes) and 24 non-diabetic patients (31 eyes) using enzyme-linked immunosorbent assay. According to the clinical stage of diabetic retinopathy, the diabetic patients were classified into non-diabetic retinopathy (11 eyes), non-proliferative diabetic retinopathy (14 eyes) and proliferative diabetic retinopathy (24 eyes). RESULTS: The aqueous levels of MIF (mean +/- sd) were 6.34 +/- 4.53 ng/ml in proliferative diabetic retinopathy, 3.22 +/- 1.71 ng/ml in non proliferative diabetic retinopathy, 1.25 +/- 0.96 ng/ml in non-diabetic retinopathy and 1.07 +/- 0.94 ng/ml in non-diabetic patients. Significant differences were found among these four groups (P < 0.0001). Aqueous MCP-1 levels were 1668.6 +/- 1442.3 pg/ml in proliferative diabetic retinopathy, 1528.6 +/- 1994.6 pg/ml in non-proliferative diabetic retinopathy, 690.2 +/- 402.1 pg/ml in non-diabetic retinopathy and 622.7 +/- 245.3 pg/ml in non-diabetic patients. Significant differences were also found among these four groups (P < 0.0001). After correcting for total aqueous protein, the ratios of MIF and MCP-1 to total protein remained significantly correlated with the clinical stage of diabetic retinopathy (P < 0.0001, P = 0.0004, respectively). The ratios of MIF to total protein significantly correlated with the ratios of MCP-1 to total protein in diabetic patients (r = 0.680, P < 0.0001). CONCLUSIONS: Aqueous MIF levels significantly correlated with aqueous MCP-1 levels and the clinical stage of diabetic retinopathy. The results suggest that MIF has a co-operative role with MCP-1 in the progression of diabetic retinopathy.     

纳米粒子载反义单核细胞趋化蛋白-1基因局部定位转染抑制兔颈动脉内膜损伤后内膜增生的研究

目的 观察纳米粒子包载反义单核细胞趋化蛋白-1（MCP-1）基因局部腔内转染对兔颈动脉球囊损伤后内膜增生的影响。方法 采用球囊导管损伤动脉内膜的方法建立兔颈动脉球囊损伤模型。用纳米粒子包载反义MCP-1基因。采用保留灌注的方法进行局部腔内定位转染。结果 聚合酶联反应检测发现重组基因整合，RNANorthern杂交观察到转基因治疗组有反义MCP-1基因表达，内源性MCP-1基因的表达受抑制，转基因治疗组内膜/中膜面积比降低42%。结论 纳米粒子可以作为转基因载体。反义MCP-1基因的表达能够有效抑制球囊损伤后新生内膜的增生。     

正常人及单纯高脂血症者血清炎症因子与血脂水平的相关性

目的:探讨正常人及单纯高脂血症者血清炎症因子与血脂水平的相关性。方法:选择单纯高脂血症者(单纯高脂血症组)64例,体检正常者(正常对照组)53例,应用酶联免疫吸附测定法检测血清高敏C反应蛋白(hs-CRP),白细胞介素(IL)-6,同时测定血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)水平。分析高脂血症者血清hs-CRP,IL-6浓度,及其与血脂的相关性。结果:单纯高脂血症组血清hs-CRP浓度(中位数1.45ng/ml),IL-6浓度(中位数0.043ng/ml)分别明显高于正常对照组的(中位数0.52ng/ml,0.013ng/ml,P0.01,0.05)。所有对象的loghs-CRP与人体质量指数(r=0.27,P0.01)、TG(r=0.337,P0.001)及TC(r=0.278,P0.05)呈显著正相关,而与HDL-C(r=-0.264,P0.01)呈显著负相关;logIL-6与TG(r=0.231,P0.05)及TC(r=0.207,P0.05)呈显著正相关;loghs-CRP与logIL-6之间无相关性(r=0.066,P=0.48)。结论:单纯高脂血症者有明显的炎症反应,而且炎症反应与血脂升高程度相关,hs-CRP是其动脉硬化发生发展的独立危险因素,IL-6可能不是诱导合成hs-CRP的因素。     

HMGB1 gene polymorphisms in patients with chronic hepatitis B virus infection

AIM: To characterize high mobility group box chromosomal protein 1(HMGB1) polymorphisms in patients infected with hepatitis B virus(HBV) and determine the different patterns in patient subgroups.METHODS: A total of 1495 unrelated Han Chinese HBV carriers were recruited in this hospital-based casecontrol study.The HMGB1 1176 G/C polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism assay.RESULTS: A significant association was observed between HMGB1 1176 G/C polymorphism and outcome of HBV infection.The subjects bearing 1176G/G genotype had an increased risk of susceptibility to chronic hepatitis B,liver cirrhosis and severe hepatitis B when compared with those bearing at least one 1176C allele.CONCLUSION: Patients with 1176G/G genotype of HMGB1 gene are more likely to have a progressive status in HBV infection.     

粒细胞-巨噬细胞集落刺激因子对大鼠急性心肌损伤血管新生的作用

目的 观察粒细胞-巨噬细胞集落刺激因子(GM-CSF)预处理对异丙肾上腺素(Iso)所致大鼠急性心肌损伤后新生血管密度的影响.方法 雄性、成年Wistar大鼠60只,体质量约190 g.按体质量将大鼠随机分成3组:对照组,GM-CSF预处理组(GM-CSF组),Iso损伤组,每组20只.GM-CSF组提前给予注射用人重组(rh)GM-CSF 5.0μg/kg,1次/d,尾静脉注射,连续3 d.在注射后的第3天,GM-CSF组和Iso损伤组同时给予Iso,按15.0 mg/kg腹腔注射,1次/d,连续3 d;对照组给予等量次生理盐水.注射后第10天.观察各组大鼠心肌损伤的病理改变和坏死灶面积;免疫组化方法测量、等大鼠心肌组织中新生血管密度指数:RT-PCR法检测大鼠心肌组织中多肽抗原(CD34)、血管内皮生长因子(VEGF)及VEGF受体(KDR/flk-1)的表达.结果 大鼠心肌坏死面积组问比较差异有统计学意义(F=10.07,P<0.01),其中GM-CSF组[(37.37 ±12.98)%]明显少于Iso损伤组[(45.51±14.96)%,P<0.05].大鼠心肌组织中新生血管密度指数组间比较差异有统计学意义(F=25.54,P<0.05),其中GM-CSF组[(3980.05±477.22)个/mm2]显著高于Iso损伤组[(2605.93 ±361.49)个/mm2,P<0.01].大鼠心肌CD34、VEGF、KDR/flk-1 mRNA表达组间比较差异有统计学意义(F值分别为17.83、4.29、4.10,P均<0.01);GM-CSF组[CD34(44.04±10.13).VEGF(49.40±11.59),KDR/flk-1(46.49 ±7.90)]均高于Iso损伤组[CD34(23.85±6.06),VEGF(31.80±8.05),KDR/flk-1(30.16±8.01).P均<0.01].大鼠心肌VEGF mRNA表达与其受体KDR/flk-1 mRNA表达呈正相关(r=0.725,R2=0.526,P<0.01).结论 GM-CSF预处理可增加大鼠心肌中新生血管密度.减轻Iso所致的大鼠心肌损伤.

Abstract：

Objective To study the effect of granulocyte-macrophage colony-stimulating factor(GM-CSF)on angiogenesis of rat with acute myocardial injury induced by isoproterenol(Iso). Methods A total of 60 adult male Wistar rats were randomly divided into 3 groups: normal control group, GM-CSF pretreatment group (GM-CSF group), and lso injury group, 20 rats in each group. GM-CSF group was administered recombinant human(rh)GM-CSF(5.0 μg/kg), through tail intravenous injection once a day for three days. Then the GM-CSF group and the Iso injury group were anesthetized by intraperitoneal injection of lso( 15.0 mg/kg) once a day for three days. The same dose of saline was administered in the same way to the control rats. Ten days after injection, pathological changes of myocardial damage and infarct area were examined by immunohistochemistry. The mRNA expression levels of polypeptide antigen (CD34), vascular endothelial growth factor (VEGF) and its receptor KDR/flk- 1 were measured by RT-PCR. Results The difference of myocardial necrosis area between groups was statistically significant(F=10.07, P < 0.01), in which GM-CSF group[(37.37 ± 12.98)%] was significantly less than Iso injury group[(45.51 ±14.96)%, P < 0.05]. The difference of myocardial neovascularization density index of rats between groups was statistically significant ( F = 25.54, P < 0.05 ), in which GM-CSF group [(3980.05 ± 477.22) No/mm2] was significantly higher than Iso injury group((2605.93±361.49)No/mm2,P<0.01).The differences of myocardial CD34,VEGF,KDR/flk-1 mRNA expression between groups were statistically significant(F=17.83,4.29,4.10,all P<0.01).Compared to Iso mjury group[CD34(23.85±6.06),VEGF(31.80±8.05),KDR/flk-1(30.16±8.01)]were higher in the GM-CSF group[CD34(44.04±10.13),VEGF(49A±11.59),and KDR/flk-1(46A9±7.90),all P<0.01].The expressions of myocardiM VEGF mRNA and its receptor KDR/flk-1 mRNA was positively correlated(r=0.725,R2=0.526,P<0.01).Conclusions GM-CSF prelreatmcnt increases the density ofnew blood vessels in myocardium,and reduces the Iso-induced myocardial injury in rats.     

下呼吸道感染患者血清与肺泡灌洗液白细胞介素-8、白细胞介素-6的动态监测

目的　探讨血清和肺泡灌洗液 (BALF)中白细胞介素 - 8(IL - 8)、白细胞介素 - 6 (IL - 6 )与下呼吸道感染的相关性 ,IL - 8和IL - 6在炎症反应中的作用。方法　采用ELISA法分别测定 36例下呼吸道感染患者 (感染组 )治疗前后、2 8例哮喘发作期患者 (哮喘组 )及 12例正常人 (对照组 )的血清和BALF的IL - 8、IL - 6水平 ,计算BALF的中性粒细胞 (PMN)和肺泡巨噬细胞 (AMs)数量。结果　感染组治疗前血清IL - 8和IL - 6水平比治疗后、哮喘组及对照组显著增高 (P <0 0 1)。哮喘组血清IL - 8和IL - 6水平比感染组治疗后明显增高 (P <0 .0 1)。BALF的细胞总数、PMN、IL - 8及IL - 6水平感染组治疗前显著比治疗后、哮喘组及对照组高 (P <0 0 1) ,哮喘组高于感染组治疗后及对照组 (P <0 0 1)。革兰阴性细菌感染患者BALF的IL - 8及IL - 6水平比革兰阳性细菌感染患者显著增高 (P <0 0 1)。感染组BALF的IL - 8水平分别与PMN和AMs呈显著正相关 (r =0 90 5 6 ,r =0 6 2 6 9,P <0 0 1)。感染组BALF的IL - 6水平与AMs呈显著正相关 (r =0 70 5 2 ,P <0 0 1)。结论　IL - 8和IL- 6参与下呼吸道感染的炎症反应 ,血清和BALF中IL - 8和IL - 6的动态变化对评价下呼吸道感染的病情和转归有一定的临床意义。     

慢性丙型肝炎患者血清IL-17A、FGF和IL-7水平与丙型肝炎病毒感染自发清除临床意义探讨*

目的 探讨丙型肝炎病毒（HCV）感染自发清除的可能机制或与血清白细胞介素-17A（IL-17A）、成纤维细胞生长因子（FGF）和白细胞介素-7（IL-7）水平的关系。方法 2017年1月~2018年1月我院接收治疗的HCV感染者70例,其中慢性丙型肝炎患者52例,HCV感染自发清除者18例,另选择30名健康人作为对照组。采用全自动电化学发光免疫分析仪检测血清抗-HCV抗体,采用ELISA法检测血清IL-17A、FGF和IL-7水平;采用RT-PCR法检测血清HCV RNA。结果 在本组慢性丙型肝炎患者中,感染HCV基因亚型以1b和2a型为主,分别占67.3%（35/52）和25%（13/52）;慢性丙型肝炎患者血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平分别为（61.1±50.5） U/L和（57.0±42.8） U/L,显著高于HCV感染自发清除者[分别为（25.0±14.2） U/L和（25.5±9.4） U/L,P<0.01];慢性丙型肝炎患者血清IL-17A、FGF和IL-7水平分别为（0.25±0.13） ng/L、（0.51±0.13）ng/L和（0.49±0.12） ng/L,均显著低于HCV感染自发清除者[分别为（0.75±0.14） ng/L、（0.93±0.11） ng/L和（0.71±0.10） ng/L,P<0.01],也显著低于健康人[分别为（1.35±0.12） ng/L、（1.49±0.12） ng/L和（0.99±0.12） ng/L,P<0.01],HCV感染自发清除者血清细胞因子水平也显著低于健康人（P<0.01）。结论 在HCV感染自发清除者中,血清 IL-17A、bFGF和IL-7水平显著高于慢性丙型肝炎患者,可能系清除病毒的原因之一,可能由于触发了主动免疫系统,导致病毒被清除,肝功能恢复正常,其真正的机制还需要进一步探讨。     

Differential Modulation of Cytokine Production by Drugs: Implications for Therapy in Heart Failure

We studied the effects of various phosphodiesterase (PDE) III inhibitors: amrinone, pimobendan and vesnarinone: a PDE IV inhibitor (Ro 20-1724) and a PDE V inhibitor (E-4021) on the production of cytokines which have been shown to depress myocardial function. Recently developed inotropic agents which inhibit PDE III activity have produced short-term hemodynamic benefits in patients with advanced heart failure, but long-term treatment with these agents has an adverse effect on survival. However, vesnarinone, which has been shown to improve survival dramatically, has an immunomodulating effect and inhibits the production of cytokines. Peripheral blood mononuclear cells obtained from healthy human subjects were stimulated with lipopolysaccharide and each PDE inhibitor was added. After 24 h of incubation, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and IL-6 in the culture supernatants were measured by an enzyme-linked immunosorbent assay. All three PDE III inhibitors, amrinone, pimobendan and vesnarinone, inhibited TNF-αproduction, but vesnarinone's inhibitory effect was the most prominent. Amrinone and pimobendan enhanced IL-1βproduction, whereas vesnarinone had no effect. Vesnarinone inhibited IL-6 production and pimobendan slightly decreased IL-6 production, whereas amrinone had no significant effect on IL-6 production. The PDE IV inhibitor, Ro 20-1724, decreased the production of IL-1βand TNF-αand also tended to inhibit IL-6 production; its modulation of cytokine production was similar to the effects of vesnarinone. Because 8Br-cAMP or 8Br-cGMP did not suppress cytokine production, the modulating effects were not considered to result from an increase in cAMP or cGMP. Differential modulation of cytokine production may play a role in the therapeutic effect in heart failure patients who are treated with drugs that have PDE-inhibitory actions. It may be important to study whether the use of dual inhibitors of PDE III and PDE IV is therapeutically more useful for the treatment of heart failure due to their immunomodulating properties.