雷公藤多甙对大鼠胶原免疫性关节炎黏膜免疫的影响

目的:观察雷公藤多甙对于大鼠胶原免疫性关节炎黏膜免疫的影响.方法:Ⅱ型胶原与完全弗氏佐剂免疫大鼠,以雷公藤多甙治疗,观察大鼠黏膜免疫各项指标.结果:雷公藤多甙可以改善CIA大鼠病理改变,降低肠道PP结中CD4/CD8比值,对脾中T细胞亚群有调节作用,并可降低关节中致炎细胞因子的表达.结论:雷公藤多甙对CIA模型大鼠有抗炎和免疫抑制的作用.     

Rate of intrusion of maxillary incisors in Class II Div 1 malocclusion using skeletal anchorage device and Connecticut intrusion arch

BackgroundNonsurgical correction of deep bite involves either extrusion of posterior teeth, intrusion of incisors, or combination of both. The introduction of skeletal anchorage device with microimplant provides near absolute anchorage without producing any untoward effects on anchor unit. Connecticut Intrusion Arch (CIA) provided an efficient system of intruding anterior segment without producing much adverse affects on anchor teeth.MethodsThe study comprised of 30 patients of Class II Div 1 malocclusion with overbite of >6 mm and required therapeutic extractions of all first premolars, randomly distributed into two groups. Group 1 was treated using orthodontic microimplants, while Group 2 treated with CIA. Lateral cephalograms were taken pre-intrusion (T1) and post-intrusion at the end of six months (T2).ResultsThe rate of intrusion was 0.51 and 0.34 mm/month for Group 1 and Group 2 respectively. The average amount of change in centroid point to PP distance and U1-SN angle was significantly higher in Group 1 compared to Group 2 (P < 0.001). The average amount of change in U6 to PP distance did not differ significantly between two study groups (P > 0.05).ConclusionThe amount of intrusion is significantly higher in SAD group. Although vertical molar positional change was higher in CIA group than the SAD group, it was not changed significantly in both treatment modalities. SAD group overall had better results and was easier in handling during intrusion.     

Tartrate-resistant acid phosphatase-positive cells in the synovial–cartilage junction and bone marrow during the progression of collagen-induced arthritis in adult rats

We investigated the time-course changes in bone destruction in rats with collagen-induced arthritis (CIA). The synovial–cartilage junction (SCJ) and epiphyseal bone marrow of the femoral posteromedial condyle in CIA rats were evaluated histologically and immunohistologically at 2, 3, 4, 6, and 8 weeks after sensitization. Two weeks after sensitization, tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells formed resorption lacunae on the lateral side of the cortical bone under the SCJ. No resorption lacunae were observed in bone marrow. Three weeks after sensitization, resorption lacunae on the lateral side of the cortical bone expanded, but no bone marrow invasion by pannus was observed. In bone marrow, many TRAP-positive multinuclear cells appeared and formed resorption lacunae in subchondral bone. Four weeks after sensitization, cortical bone was destroyed, and pannus had invaded the bone marrow. After six weeks, trabecular bone and subchondral bone plate were extensively resorbed by TRAP-positive cells. Bone destruction in CIA began with the appearance of TRAP-positive cells on the lateral side of the cortical bone under the SCJ, followed by the TRAP-positive multinuclear cells in bone marrow, which were morphologically unconnected to the SCJ lesions. These histological findings suggested that bone destruction in the early stage of arthritis occurred in two anatomically different regions.     

断藤益母汤对类风湿关节炎成纤维样滑膜细胞MEKK2及CIA小鼠关节炎的影响

目的:为了研究断藤益母汤(DTYMD)在类风湿关节炎中对丝裂原活化蛋白激酶(MAPK)上游激酶的调控作用,阐明DTYMD抗炎的分子机制。方法:培养成纤维样滑膜细胞,将细胞分为空白组,模型组,DTYMD高、中、低质量浓度组(1 000,800,600 mg·l~(-1)),甲氨蝶呤(MTX)组(20μmol·l~(-1))组,采用蛋白免疫印迹法(Western blot),实时荧光定量聚合酶链式反应(Real-time PCR)对丝分裂原活化蛋白激酶激酶激酶2(MEKK2)的蛋白和mRNA表达进行分析。将42只雄性DBA/1J小鼠随机分为6组,每组7只,分别为正常组,模型组,MTX组(2 mg·kg~(-1)),DTYMD低、中、高剂量组(6. 25,12. 5,25 mg·kg~(-1))。除正常组外,其他5组均采用二次免疫法构建胶原诱导型关节炎(CIA)模型。给药结束后,取小鼠后肢踝关节行苏木素-伊红(HE)染色并进行关节病理评分。结果:与模型组比较,DTYMD以浓度依赖方式抑制成纤维样滑膜细胞活性(P 0. 01);与空白组比较,模型组细胞增殖率升高(P 0. 01)。与模型组比较,DTYMD高、中质量浓度组降低MEKK2蛋白及mRNA的表达(P 0. 05,P 0. 01)。与模型组比较,DTYMD不同剂量组均降低细胞基质金属蛋白酶-1(MMP-1),肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6)的表达(P 0. 01);与空白组比较,模型组MMP-1,IL-6,TNF-α表达明显上升(P 0. 05,P 0. 01)。在动物实验中,与模型组比较,DTYMD高、中剂量组可以降低CIA小鼠关节肿胀度(P 0. 05,P 0. 01);与正常组比较,模型组小鼠二次免疫后关节明显肿胀(P 0. 05)。在CIA小鼠踝关节HE染色中,与空白组比较,模型组小鼠病理学评分升高(P 0. 01);与模型组比较,DTYMD高、中剂量小鼠关节病理评分明显下降(P 0. 05,P 0. 01)。结论:DTYMD可能通过下调MEKK2对细胞因子IL-6,TNF-α,MMP-1负性调控,从而缓解类风湿关节炎的炎症反应。     

Immune checkpoints and the regulation of tolerogenicity in dendritic cells: Implications for autoimmunity and immunotherapy

The immune system is responsible for defending the host from a large variety of potential pathogens, while simultaneously avoiding immune reactivity towards self-components. Self-tolerance has to be tightly maintained throughout several central and peripheral processes; immune checkpoints are imperative for regulating the immunity/tolerance balance. Dendritic cells (DCs) are specialized cells that capture antigens, and either activate or inhibit antigen-specific T cells. Therefore, they play a key role at inducing and maintaining immune tolerance. DCs that suppress the immune response have been called tolerogenic dendritic cells (tolDCs). Given their potential as a therapy to prevent transplant rejection and autoimmune damage, several strategies are under development to generate tolDCs, in order to avoid activation and expansion of self-reactive T cells. In this article, we summarize the current knowledge relative to the main features of tolDCs, their mechanisms of action and their therapeutic use for autoimmune diseases. Based on the literature reviewed, autologous antigen-specific tolDCs might constitute a promising strategy to suppress autoreactive T cells and reduce detrimental inflammatory processes.     

中药熏蒸疗法对Ⅱ型胶原蛋白诱导型关节炎大鼠关节病理改变的影响

目的 研究中药熏蒸疗法对Ⅱ型胶原蛋白诱导的关节炎(CIA)模型大鼠关节病理改变的影响.方法 用小牛源Ⅱ型胶原复制CIA模型.清洁级雄性Wistar大鼠随机分为正常组、模型组、水熏组、低熏组、高熏组,正常组和模型组常规喂养,不作熏蒸处理;水熏组给予(57±1)℃蒸馏水熏蒸,蒸气温度为(39±1)℃;低熏组给予水熏组相同温度的3.33%中药液熏蒸;高熏组给予水熏组相同温度的6.67%中药液熏蒸,造模第41日处死大鼠,获取完整膝关节.光镜下观察炎性细胞浸润、纤维组织增生及滑膜细胞增生情况.结果 中药熏蒸疗法对CIA大鼠骨关节组织的炎性细胞浸润、纤维组织增生及滑膜细胞增生有明显抑制作用.3种病理改变的总积分与模型组差异显著.结论 中药熏蒸疗法治疗类风湿性关节炎的机制可能与抑制炎性细胞浸润、纤维组织增生及滑膜细胞增生有关.     

防风色原酮提取物对大鼠胶原诱导性关节炎的影响

目的:研究防风色原酮提取物对大鼠胶原诱导性关节炎(collagen Ⅱ-induced arthritis,CIA)的防治作用及初步机制。方法:Ⅱ型胶原二次免疫诱导大鼠CIA模型,初次免疫前3d分别以0.21,0.42,0.84g·kg^-1量ig防风色原酮提取物,动态观察大鼠关节炎积分和发病率;免疫后35d取材,观察关节组织病理学和放射影像学变化;酶联免疫吸附法检测血清抗Ⅱ型胶原抗体IgG和IgM水平;放射免疫分析法检测血清中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)含量。结果:防风色原酮提取物能降低大鼠关节炎积分和发病率,抑制血清中IgG和IgM含量,减轻关节滑膜、软骨和骨的组织病理学变化及X光片的骨破坏程度,降低血清IL-1β,TNF-α和IL-6水平。结论:防风色原酮提取物能控制大鼠CIA病情的发生发展,其机制可能与对促炎细胞因子的有效抑制有关。     

骨碎补总黄酮对胶原诱导大鼠类风湿关节炎骨破坏治疗作用的实验研究

目的建立模拟类风湿关节炎(RA)发病的胶原诱导关节炎(CIA)大鼠模型,明确骨碎补总黄酮对CIA大鼠关节局部骨破坏的改善作用,为临床提供实验依据。方法利用皮下注射牛Ⅱ型胶原诱导Wistar大鼠发病,建立CIA大鼠模型。将大鼠随机分为正常对照组(10只)、灭菌用水治疗组(10只)、骨碎补总黄酮治疗组(10只)。每只大鼠均在炎症分值达到2分及以上时开始治疗,分别在治疗4周和8周,取胫骨上段做硬组织切片,观察胫骨上段骨小梁变化及骨量变化情况。结果骨碎补总黄酮具有明显抑制CIA大鼠关节周围骨量丢失的作用,且其抑制骨量减少主要是通过抑制骨小梁数量减少来实现的,与抑制骨小梁宽度丢失关系较小。结论骨碎补总黄酮能明显抑制CIA大鼠关节侵蚀及关节周围骨丢失。