目的:从CD4+T细胞DNA甲基化变化探讨雷公藤甲素治疗系统性红斑狼疮(SLE)的作用机制.方法:将8只C57BL/6小鼠作为对照组,24只MRL/lpr狼疮小鼠随机分为模型组、激素组、雷公藤甲素组,每组8只.对照组和模型组灌胃蒸馏水,激素组灌胃0.5 mg/mL浓度的醋酸泼尼松片混悬液,雷公藤甲素组灌胃30μg/mL雷公藤甲素混悬液,连续干预8周.ELISA检测小鼠尿蛋白、血清抗双链DNA抗体和TNF-α水平;HE染色观察肾脏病理改变;Methyflash? DNA甲基化试剂盒检测脾脏CD4+T细胞全基因组DNA甲基化水平;Methyl Target?目标区域甲基化测序检测CD11a、CD70基因启动子区甲基化水平;RT-PCR法检测脾脏CD4+T细胞miR-126-3p及DNMT1、CD11a、CD70mRNA表达;Western blot法检测DNMT1、CD11a、CD70蛋白表达.结果:与模型组比较,雷公藤甲素组小鼠的尿蛋白、血清抗双链DNA抗体和TNF-α水平显著降低(P＜0.01),肾脏病理损伤改善,CD4+T细胞全基因组DNA甲基化水平显著升高(P＜0.01),CD70基因启动子区甲基化水平显著升高(P＜0.01),miR-126-3p表达下降(P＜0.05),DNMT1 mRNA及蛋白表达水平增高(P＜0.01),CD11a、CD70 mRNA及蛋白表达呈下降趋势.结论:雷公藤甲素可能通过调控CD4+T细胞DNA甲基化状态而改善SLE病情,其作用靶点可能是miR-126-3p/DNMT1通路.

目的:从CD4+T细胞C D229/C D25轴探讨解毒祛瘀滋肾方治疗系统性红斑狼疮(SLE)的作用机制.方法:24只MRL/lpr狼疮小鼠随机分成模型组、激素组、中药组,各8只,8只C57BL/6小鼠作为空白组.中药组予2g/mL解毒祛瘀滋阴方水煎剂灌胃,激素组予0.5mg/mL醋酸泼尼松片混悬液灌胃,模型组和空白组予蒸馏水灌胃,连续干预8周.观测小鼠尿蛋白、血清抗双链DNA抗体、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)、白细胞介素-2(IL-2)水平,HE染色观察肾脏病理改变;RT-PCR和Western blot分别检测小鼠脾脏C D4+T细胞CD229、CD25 mRNA和蛋白的表达水平.流式细胞术检测小鼠脾脏CD4+T细胞调节性T细胞(Treg)比率.结果:与模型组比较,中药组小鼠肾脏病理损伤明显改善,尿蛋白、血清抗双链DNA抗体、TNF-α、TGF-β水平显著降低(P＜0.01),IL-2水平显著升高(P＜0.01);CD229、CD25 mRNA表达水平显著升高(P＜0.01),蛋白表达上调;Treg比率升高(P＜0.01).结论:解毒祛瘀滋肾方可能是通过调控CD229/C D25轴,促进Treg增加进而改善SLE病情.

系统性红斑狼疮是一种难治性系统性自身免疫性疾病,病情复杂,症状多变,而皮肤红斑是其临床最常见的症状之一.“斑为阳明热毒”是温病学说对发斑辨治的纲领,是对斑出现的病机、病位的总结概括.文章结合中医学相关理论,阐释“斑为阳明热毒”的理论内涵,从“斑为阳明热毒”分析系统性红斑狼疮发病的病因病机,并初步探讨“斑为阳明热毒”对中医药治疗系统性红斑狼疮的指导作用.

目的:基于文献整理探讨中医药治疗系统性红斑狼疮(Systemic lupus erythematosus,SLE)的证候分类及用药规律演变.方法:检索中国知网(CNKI)、维普中文科技期刊数据库、中国学术期刊数据库中中医药治疗SLE的相关文献,时间限定为从数据库建立至2018年7月.对证型及药物进行分类并统计分析.结果:纳入文献725篇,总结归纳高频证型11个,出现频次最高的五个证型分别为热毒炽盛证、脾肾两(阳)虚证、阴虚内热(火旺)证、肝肾两(阴)虚证、气阴两虚证,累计频率62.11％.1965-2018年间,阴虚内热(火旺)证呈明显增长趋势;热毒炽盛证、脾肾两(阳)虚证及气阴两虚证在1965-2010年间呈增长趋势,在2011-2018年间呈下降趋势;肝郁气滞(脾虚)证在1965-2018年间呈下降趋势;其余证型均呈动态波动.涉及组方1 522个,药物309味,使用15 910次,总使用频率最高的5味药分别为生地黄、牡丹皮、茯苓、黄芪、甘草,总累计频率16.42％.使用频率最高药类为清热药和补虚药;生地黄、牡丹皮等清热药的使用频率趋势与热毒炽盛证保持一致,不同年份高频用药大致相似,用药频率存在较小差异.结论:SLE在内以阴阳亏虚为主,在外与热毒侵袭相关,属于本虚标实,其发展与生态环境、社会环境、药物使用等紧密相关,治当以清热凉血、活血祛瘀、益气养阴,并结合个人体质及环境变化辨证治疗.

[目的]探讨透热转气法治疗系统性红斑狼疮(systemic lupus erythematosus,SLE)的理论依据及临床应用.[方法]通过分析透热转气法的理论内涵,结合SLE的病因病机和发病特点,阐述透热转气法治疗SLE的理论依据和临证应用,并举典型医案佐证.[结果]透热转气法是指通过宣畅气机,使入营之邪透出气分而解的方法,是温病学的重要治法.SLE的病因病机以肾精亏虚、温毒侵袭及瘀血内阻为主,其发病特点与温病有相似之处,根据SLE患者病情活动期和缓解期的特点可灵活运用透热转气法.所举案例一辨证属热伏血分、气阴耗伤,治以清热凉血、养阴透邪;案例二辨证属营分有热、肾精亏虚,治以清营透热、益肾固精,方中均配伍轻清透邪药以条畅气机、清透邪热,取得良好的疗效.[结论]运用透热转气法治疗SLE发挥了中医药治疗SLE的优势,符合临床实际,对于指导临床应用具有重要的意义.

OBJECTIVE:To determine the effective dosage and formulation of agkistrodon in collagen-induced arthritis (CIA) rats.METHODS:CIA was induced by injection of collagen in complete/incomplete Freund's adjuvant. Agkistrodon decoction, agkistrodon powder, and agkistrodon wine were administered daily starting from the onset of arthritis. Paw swelling degree was measured by using a volume-measuring instrument every 7 days after primary immunization. Arthritis index was measured and calculated using the "five scoring method" every 7 days. The levels of serum interleukin-1ß (IL-1ß) and type II collagen IgG antibodies were detected by enzyme-linked immunosorbent assay. Finally, all ankles were removed, and X-ray radiography was performed with In-vivo Imaging System FX. Samples were counterstained with hematoxylin and eosin for analysis.RESULTS:Among the various dosage formulations of agkistrodon, high-dose powder, which was equivalent to an amount of 6 g/day in adults, showed better effects on the inhibition of joint swelling and reduction of arthritis index score. The relatively low levels of serum IL-1 and anti-type II collagen IgG antibodies, as well as the X-ray radiography and pathology results, further proved the superiority of the high-dose powder over the other formulations. The effect of decoction on inhibiting joint swelling was inversely proportional to the dosage. Other effects, such as reduction of arthritis index score and the levels of serum IL-1 and anti-type II collagen IgG antibodies, were directly proportional to the dosage. While the use of large dose agkistrodon wine led to negative effects.CONCLUSION:These data highlight the potential function of high-dose agkistrodon powder, which was equivalent to an amount of 6 g/day in adults. The powder can quickly relieve the symptoms of rheumatoid arthritis and prevent aggravation of disease, especially during the early period.

By sorting out the ancient literature about arthralgia syndrome,the origin and the development of it were researched from 3 aspects including the disease name,the etiology and pathogenesis and the treatment methods. The historical development of arthralgia syndrome was analyzed. Meanwhile,these knowledges were summarized including the deficiency of vital qi,the external evil invasion and the blockage of phlegm and blood stasis by Chinese medicine of the past dynasties. The treatments for different periods of it were inquired in purpose of increase our thinking and guideing clinical.