三氧化二砷对狼疮小鼠存活率和自身免疫反应的影响(英文)

目的探讨三氧化二砷(ATO)在治疗系统性红斑狼疮中的应用价值并探讨其作用机制。方法① BXSB狼疮小鼠随机分为ATO治疗组和对照组,每组17只。ATO治疗组隔日ip ATO0.4 mg·kg-1至d105,实验持续至d 210结束,观察两组小鼠的存活率,采用ELISA法检测小鼠血清IgG和抗ds-DNA抗体水平。②另外20只BXSB狼疮小鼠,同上分组处理,至d 90处死取脾和肾组织,提取总RNA,用RT-PCR方法检测脾和肾组织中干扰素γ(IFN-γ)mRNA的表达。结果至d210,ATO治疗组小鼠死亡8只,对照组死亡13只。至d90和d105,治疗组小鼠血清抗ds-DNA抗体(A450 nm)分别为0.335±0.011和0.223±0.017,对照组分别为0.688±0.016和0.683±0.014。至d90 ATO治疗组小鼠脾和肾组织IFN-γ mRNA表达较对照组亦明显下降。至d 105,ATO治疗组血清IgG水平较对照组明显下降,分别为(4.9±1.3)和(6.9±1.0)g.L-1。结论 ATO可提高BXSB狼疮小鼠的存活率,降低血清IgG和抗ds-DNA抗体水平,抑制脾和肾组织IFN-γ mRNA的表达。     

来氟米特对MRL/1pr小鼠肾脏JAK/STAT信号转导途径的影响

目的 探讨来氟米特对MRL/1pr狼疮小鼠肾脏JAK/STAT 1信号转导途径的影响.方法 14只12周龄雌性MRL/1pr狼疮小鼠随机分为空白对照组和治疗组(来氟米特35 mg·kg-1·d-1×8周).检测小鼠肾脏磷酸化SrAT 1(p-STAT 1)蛋白及细胞信号传导抑制因子(SOCS)-1 mRNA表达情况,并观察小鼠体重、24-h尿蛋白、血浆抗双链DNA(ds-DNA)抗体浓度、肾组织病理改变及肾小球免疫荧光变化.结果 治疗组小鼠24-h尿蛋白及血浆抗ds-DNA抗体浓度均明显低于对照组(P<0.01),肾脏p-STAT 1蛋白及SCCS-1 mRNA表达均低于对照组(P<0.01);肾组织病理明显改善.结论 来氟米特能抑制肾脏JAK/STAT 1信号转导途径,对MRL/1pr狼疮小鼠有治疗作用.     

来氟米特对MRL/lpr狼疮鼠治疗作用的研究

目的 研究来氟米特( Leflunomide,LEF)对MRL/lpr狼疮鼠免疫状况的影响.方法 将MRL/lpr狼疮鼠随机分为3组:LEF组(10mg·kg-1·d)、生理盐水(NS)组(0.25mL)和环磷酰胺(CTX)组(50mg· kg-1·qw).每组各6只,CTX组隔日腹腔注射,其余两组每天灌胃,给药2个月后处死,ELISA法测各组小鼠外周血测血清ANA、抗ds-DNA抗体水平,考马斯亮蓝法测24h尿蛋白定量和流式细胞术测脾脏淋巴细胞亚群比例.结果 ①MRL/lpr小鼠LEF治疗组血清抗ds-DNA抗体水平和24h尿蛋白量较NS组明显降低(P＜0.01和P＜0.05)；②LEF治疗组小鼠NK细胞百分比明显高于NS对照组(P＜0.05),而CD19、CD3、CD3CD4阳性细胞百分比显著低于NS对照组(P＜0.05或P＜0.01).结论 LEF能抑制MRL/lpr狼疮鼠T、B淋巴细胞活化同时上调NK细胞功能,减少体内自身抗体和蛋白尿的产生,从而达到治疗狼疮的目的.     

清化狼疮汤对MRL/lpr小鼠血清ANA、SIL-2R的影响

目的:研究中药清化狼疮汤对MRL/lpr小鼠血清抗核抗体(ANA)、SIL-2R的影响.方法:取MRL/lpr♀小鼠40只和♂小鼠8只,随机分成4组,分别予以胃饲生理盐水(模型组)、清化狼疮汤混悬液(中药组)、泼尼松(西药组)和清化狼疮汤混悬液加泼尼松(中西药组).30 d后,免疫荧光法检测小鼠血清ANA滴度,单克隆抗体技术酶联免疫吸附(ELISA)双抗体夹心法检测小鼠血清SIL-2R表达水平.结果:中药组、西药组和中西药组MRL/lpr小鼠的血清ANA滴度和SIL-2R表达水平,均明显低于生理盐水组(P＜0.01或P＜0.05).结论:清化狼疮汤可以降低MRL/lpr小鼠血清ANA滴度和SIL-2R的表达水平.     

黄芪多糖对系统性红斑狼疮小鼠免疫调节的影响

目的 探讨黄芪多糖对系统性红斑狼疮MRL/lpr小鼠免疫功能的影响及作用机制.方法 将20只MRL/lpr狼疮小鼠依据随机数字表法分为模型组和药物组,每组各10只,另选择10只雌性C57BL/6小鼠作为对照组.药物组采用黄芪多糖治疗,对照组和模型组均采用同等剂量生理盐水治疗.比较各组小鼠的自身抗体水平.采用流式技术法测...     

三氧化二砷对小鼠肝癌生物学行为的影响

目的研究三氧化二砷对HepA小鼠肝癌生长、血管生成及侵袭与转移特性的影响。方法建立皮下种植肝癌小鼠模型,用药后观察小鼠肿瘤体积变化及抑瘤率;利用免疫组织化学观察移植瘤中血管内皮生长因子（VEGF）,对移植瘤的微血管密度（MVD）进行计数。结果三氧化二砷对小鼠肝癌瘤体体积和抑瘤率均具有抑制作用;三氧化二砷能抑制肿瘤新生血管生成,降低VEGF的表达,并能降低肿瘤MVD,与未用药对照组相比差异均有统计学意义（P〈0．05）。结论三氧化二砷能缩小肿瘤体积、增加抑瘤率,并能降低VEGF的表达,减少微血管密度。     

TACI-Ig对MRL/lpr小鼠的治疗作用及其对小鼠肾组织JAK1-STAT1信号通路的影响

目的研究TACI-Ig对MRL/lpr小鼠的治疗作用以及TACI-Ig对狼疮性肾炎肾组织JAK1-STAT1信号通路活化的影响。方法将MRL/lpr红斑狼疮转基因小鼠随机分成6组,即模型组、TACI-Ig 3个剂量治疗组(3.75、7.5、15 mg.kg-1)组、强的松阳性对照组和IgG-Fc阴性对照组,另选用BALB/c小鼠作为正常对照组。除强的松组每日灌胃给药外,其余各组隔日皮下注射给药,共计8周,模型组和正常组给予生理盐水。观察TACI-Ig对MRL/lpr小鼠一般体征、损伤指数的影响,目测半定量尿蛋白试纸法检测动物的尿蛋白变化,HE染色法观察肾组织病理学改变情况,全自动生化分析仪检测血清中肌酐和尿素氮的水平,ELISA法检测血清中BLyS、IL-10和IFN-γ的水平,免疫组化法检测肾脏磷酸化的JAK1和STAT1的表达分布情况。结果 TACI-Ig(7.5、15mg.kg-1)皮下注射给药8周可明显降低模型小鼠的尿蛋白水平和损伤指数;有效改善肾小球系膜细胞增生和肾小球纤维化,明显减轻炎性细胞浸润;TACI-Ig给药可明显降低小鼠血清中的肌酐和尿素氮水平以及血清中BLyS、IL-10、IFN-γ等细胞因子水平。免疫组化结果显示模型组小鼠的肾脏磷酸化的JAK1和STAT1蛋白的表达明显升高,在肾小球、肾间质中呈强阳性表达,TACI-Ig给药后可使其表达明显降低。结论 TACI-Ig可明显改善MRL/lpr小鼠红斑狼疮样的临床表现和肾脏病理特征,降低血清中细胞因子和肾组织中磷酸化JAK1、STAT1蛋白的表达水平,这可能是TACI-Ig治疗狼疮性肾炎的机制之一。     

三氧化二砷对小鼠免疫功能的影响

三氧化二砷对小鼠免疫功能的影响刘佳吴克枫俞红李锦兰高敏（贵州省卫生防疫站，贵阳５５０００４）用Ａｓ２Ｏ３染毒昆明种雌性小鼠，采用０．１，０．７，４ｍｇｋｇ－１３个剂量组，以２５ｍｇｋｇ－１的环磷酰胺作为阳性对照，经口连续染毒２２ｄ观察Ａｓ２Ｏ３对小鼠...     

商陆皂苷甲对MRL/lpr小鼠iTr35细胞及其相关细胞因子表达的影响

摘要：目的 观察商陆皂苷甲（EsA）对MRL/lpr小鼠的治疗作用和体内iTr35（CD4+Foxp3-IL-12p35+IL-27EBI3+） 细胞、白细胞介素（IL）-35及IL-17表达的影响,探讨EsA治疗狼疮性肾炎的可能机制。方法 将24只16周龄、雌性 MRL/lpr小鼠随机分为模型对照组、EsA组和EsA+IL-12p35抗体组,分别腹腔注射给药,每日1次,4周后处死小鼠, 进行尿蛋白/肌酐值、血肌酐浓度、IL-35、IL-17、iTr35细胞比例、肾脏病理的检测。结果 3组小鼠尿蛋白/肌酐值、血 肌酐浓度、IL-35、IL-17、iTr35差异有统计学意义（P＜0.05）,其中模型对照组尿蛋白/肌酐值、血肌酐浓度、IL-17含量 最高,其次为EsA+IL-12p35抗体组,EsA组最低;相反,EsA组中IL-35、iTr35水平最高,其次为EsA+IL-12p35抗体 组,模型对照组最低;与模型对照组相比,EsA组和EsA+IL-12p35抗体组小鼠肾脏病理表现有一定改善。结论 狼 疮性肾炎小鼠血清中存在IL-35、IL-17的表达异常,EsA对狼疮性肾炎有效,其机制可能是通过调节IL-35、IL-17及 iTr35的表达而发挥作用的。     

基于HPV16的新型伪病毒治疗MRL/lpr小鼠狼疮性肾炎的实验研究

目的 构建基于人乳头状病毒(human papilloma virus,HPV)16型的新型伪病毒,探讨对MRL/Ipr,小鼠狼疮性肾炎的治疗作用,为临床治疗系统性红斑狼疮提供实验依据.方法 将12只3月龄MRL/Ipr狼疮小鼠随机均分为治疗组和对照组,治疗前后测定尿蛋白、血清尿素氮、肌酐及抗ds-DNA抗体滴度.结果 治疗组小鼠治疗后的尿蛋白、血清尿素氮、肌酐及抗ds-DNA抗体均下降,与治疗前有显著性差异(P＜0.05),而对照组治疗前后无显著性差异(P＞0.05),并且治疗组小鼠的平均生存期比对照组明显延长(p＜0.05).结论 基于人乳头状病毒16型的新型伪病毒可显著改善MRL/Ipr小鼠的免疫状况和肾脏功能,提高平均生存期.该研究结果为临床治疗系统性红斑狼疮提供了新的启示.     

Gallium nitrate suppresses lupus in MRL/lpr mice

Gallium (Ga) nitrate, a drug which prevents a variety of experimental autoimmune diseases, was investigated in a murine model of systemic lupus erythematosus (SLE). In one experiment, female MRL/Mp lpr/lpr (MRL/lpr) mice were randomized into 2 groups of 6:1) vehicle (trisodium citrate) and 2) Ga. Subcutaneous injections began at 3 weeks of age and continued weekly until the mice were euthanized a week after the thirteenth injection. The loading dose of Ga (calculated as elemental Ga) was 45 mg/kg, followed by 15 mg/kg/week. In another experiment (n = 18) with 3 males and 3 females per group, mice received 1) vehicle, 2) Ga × 1 (one 45 mg/kg dose), and 3) Ga × 13. In the experiment with 12 mice, axillary lymph nodes from Ga-treated mice were significantly smaller than those from vehicle-treated mice (91 ± 42 and 360 ± 358 mg respectively, mean ± SD), and spleens as well as lymph nodes from the former showed significantly less lymphoid infiltrate. In the experiment with 18 mice, prescapular lymph nodes weighed 312 ± 98, 217 ± 52, and 42 ± 34 mg, and spleens weighed 732 ± 492, 409 ± 164, and 192 ± 93 mg in the groups which received vehicle, Ga × 1, and Ga × 13 respectively. Control mice had significantly more lymphoid infiltrates in the lungs, spleen, and lymph nodes and, unlike Ga × 13 mice, exhibited glomerulitis and renal vasculitis. Within groups, females developed more severe disease than males. The Ga × 13 group had increased percentages of CD4-bearing and CD8-bearing lymphocytes in lymph nodes and increased CD4-bearing lymphocytes in the spleen, with an increased proliferative response to mitogen stimulation in vitro in lymph nodes, although not in the spleen. The Ga × 13 group also gained less weight and developed osteosclerosis. Although preliminary, our findings suggest that clinical trials with Ga in SLE are merited. Received: 9 January 1997 / Accepted: 30 May 1997     

CD4(+) T-cell activation and induction of autoimmune hepatitis following trichloroethylene treatment in MRL+/+ mice.

Exposure to relatively high levels of trichloroethylene has recently been shown to accelerate the development of an autoimmune response in the autoimmune prone MRL+/+ mice. The trichloroethylene-induced autoimmune response was associated with an increase in activated CD4(+) T cells, producing Th(1)-like cytokines. The present study was conducted to determine whether lower, more occupationally relevant doses of trichloroethylene could also promote autoimmunity, in MRL+/+ mice, and if so, to investigate the mechanism of this accelerated autoimmune response. In addition, histological studies were performed to determine if trichloroethylene was capable of producing pathological markers consistent with an autoimmune disease. Trichloroethylene was administered to mice in the drinking water at 0, 0.1, 0.5, and 2.5 mg/ml for 4 and 32 weeks. There was a significant increase above controls in serum antinuclear antibody (ANA) levels following 4 weeks of both 0.1 and 0.5 mg/kg/day of trichloroethylene. After 32 weeks of treatment, ANA levels were elevated and equal in all groups. The kinetics of the ANA response indicated that trichloroethylene accelerated the innate autoimmune response in the MRL+/+ mice. There was a dose-related increase in the percentage of activated CD4(+) T cells in both the spleens and lymph nodes of mice treated for 32 weeks with trichloroethylene when compared to controls. CD4(+) T cells isolated from MRL+/+ mice after either 4 or 32 weeks of treatment with trichloroethylene secreted inflammatory or Th(1)-like cytokines. Following 32 weeks of trichloroethylene treatment, there was a significant increase in hepatic mononuclear infiltration localized to the portal region, a type of hepatic infiltration consistent with autoimmune hepatitis. Taken collectively, these data suggest that exposure to occupationally relevant concentrations of trichloroethylene can accelerate an autoimmune response and can lead to autoimmune disease. The mechanism of this autoimmunity appears to involve, at least in part, activated CD4(+) T cells that then produced inflammatory cytokines.     

解毒祛瘀滋阴药对MRL／lpr小鼠外周血淋巴细胞凋亡及线粒体跨膜电位的影响

目的探讨解毒祛瘀滋阴中药对MRL／lpr小鼠外周血淋巴细胞凋亡及其线粒体跨膜电位的影响。方法80只MRL／lpr小鼠随机分为：模型组：20只,灌胃0．9％氯化钠注射液;中药组：20只,灌胃解毒祛瘀滋肾中药煎剂;西药组：20只,灌胃强的松混悬液;中西药组：20只,中西药分别灌胃;正常组：昆明小鼠选用20只,0．9％氯化钠注射液灌胃,均每日1次,每次0．5ml。连续饲养用药12周后取血,以梯度离心法分离提纯外周血淋巴细胞（PBLC）,培养48h,流式细胞仪检测凋亡率及其线粒体跨膜电位水平。结果正常组、中药组、西药组和中西药组PBLC0和48h凋亡率高于模型组,差异有显著性（P〈0．05,P〈0．01）。0小时西药组、正常组与中西药组的凋亡率无明显差异（P〉0．05）,但中药组和模型组与中西药组比较,差异有显著性（P〈0．05）;48h西药组与中西药组的凋亡率有明显差异（P〈0．05）,中药组和模型组与中西药组比较,差异有显著性（P〈0．01）;正常组、中药组、西药组和中西药组PBLC线粒体跨膜电位水平水平均明显低于模型组,差异有显著性（P〈0．05和P〈0．01）;西药组与中西药组低于正常组,模型组高于正常组,且比较均差异有显著性（P〈0．05和P〈0．01）;中药组与正常组之间差异无显著性（P〉0．05）;西药组与中西药组之间差异无显著性（P〉0．05）。结论解毒祛瘀滋阴药能增加MRL／Ipr小鼠的PBLC凋亡率并下调其线粒体跨膜电位水平。     

三氧化二砷对小鼠过敏性哮喘的治疗作用及机制

目的 :研究三氧化二砷对小鼠过敏性哮喘的治疗作用及对脾T细胞周期和Bcl 2基因表达的影响。方法 :用卵蛋白建立小鼠过敏性哮喘模型 ,收集肺泡灌洗液 (BALF) ,直接计算白细胞总数和分类 ,双缩脲法检测总蛋白含量 ,应用Medlab生物信号采集系统软件检测小鼠肺功能 ,流式细胞术和免疫荧光法检测脾及BALF中T细胞数、T细胞周期和Bcl 2基因表达的变化。结果 :三氧化二砷可使BALF中总蛋白含量下降 ,白细胞总数减少 ,嗜酸细胞和淋巴细胞减少 ,改善哮喘小鼠肺功能 ;使脾及BALF中T细胞数降低 ;在 1.15mg·kg-1的剂量时可诱导脾T细胞凋亡 ,在 4 .6 0mg·kg-1的剂量时抑制其活化增殖 ;可下调脾T细胞Bcl 2基因表达。结论 :三氧化二砷有平喘作用 ,其作用机制可能与其调节T细胞的激活与凋亡 ,下调Bcl 2基因表达有关。