Objective: To explore the mechanism of Huatan Sanjie Fang(HTSJ) in regulating goiter in Graves’ disease(GD) mice by detecting key factors of the Hippo signaling pathway.Methods: A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice. Successful mouse models were then randomly divided into a model group, methimazole(MMI) group, and HTSJ group, and fed with deionized water, MMI(4.5 mg/kg per day), and HTSJ(35.10 g/kg per day), respectively, for 10 weeks. Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining. Radioimmunoassay was used to detect serum total thyroxine(T4) and thyrotrophin-receptor antibody(TRAb) levels. The relative expression of mRNA of Mst1, YAP, and TAZ were detected by quantitative real-time polymerase chain reaction, while the protein expression of Mst1, YAP, TAZ, pMst1, and pYAP were detected by western blot.Results: After 10 weeks of drug intervention, goiter and other pathological changes in the HTSJ group significantly improved compared with the model group, and the levels of serum T4 and TRAb significantly decreased(P =.002, P <.001, respectively). Decreased mRNA expression of Mst1, YAP, and TAZ, the key factors of the Hippo signaling transduction pathway, was also observed(P =.002, P =.022, P <.001,respectively). In contrast, protein expression of Mst1(P =.046), pMst1(P =.026), and p YAP(P =.004)increased, while protein expression of YAP and TAZ decreased(P =.041, P <.001, respectively).Conclusion: HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway.
目的 观察葛根芩连汤对2,4-二硝基氟苯(2,4-dinitrofluorobenzene,DNFB)诱导的特应性皮炎(atopic dermatitis,AD)模型小鼠的干预作用及潜在作用机制.方法 24只雄性BALB/c小鼠随机分为正常组、模型组、中药组(葛根芩连汤治疗)和对照组(糠酸莫米松治疗).DNFB反复刺激皮肤致敏诱导AD小鼠模型.观测各组小鼠皮损评估、皮肤组织病理学、皮肤pH值、经皮水分流失、搔抓行为及血清总免疫球蛋白E(immunoglobulin E,IgE)、白细胞介素6(interleukin-6,IL-6)、白细胞介素10(interleukin-10,IL-10)含量.逆转录—聚合酶链式反应(quantitative Real-time PCR,qRT-PCR)法测定丝聚合蛋白、密封蛋白1的mRNA的表达;蛋白免疫印迹法(Weston blot,WB)检测丝聚合蛋白、密封蛋白1的蛋白表达水平.结果(1)治疗前,与正常组相比,模型组背部皮肤有明显的红斑水肿,并可见结痂、鳞屑、皮肤肥厚增生;搔抓次数明显增多,经皮失水及皮肤pH值显著升高;经治疗,与模型组比较,中药组与对照组皮肤损伤情况改善,搔抓次数、经皮失水、皮肤pH值显著降低(P<0.05);(2)治疗前,模型组小鼠血清总IgE、IL-6、IL-10水平均与正常组有显著差异;经治疗,中药组、对照组总IgE、IL-6水平与模型组相比含量降低(P<0.05);(3)与正常组比较,模型组qRT-PCR显示丝聚合蛋白、密封蛋白1的表达水平降低;WB显示丝聚合蛋白、密封蛋白1蛋白的含量降低;经治疗,中药组、对照组丝聚合蛋白、密封蛋白1的基因表达水平增高;丝聚合蛋白、密封蛋白1蛋白含量增高(P<0.05);(4)皮肤病理学显示与正常组相比,模型组表皮层存在不完全角化,颗粒层和棘层皮肤增厚,表皮、真皮层均有大量炎细胞浸润;经治疗,中药组及对照组小鼠表皮层角化不全程度较轻,颗粒层、棘层皮肤轻微增厚,炎细胞浸润减轻.结论 葛根芩连汤可以减轻AD模型小鼠皮损程度,减少搔抓次数,有效降低经皮失水、皮肤pH值,下调小鼠血清IgE、IL-6水平,上调丝聚合蛋白、密封蛋白1的表达,抑制炎症反应和改善皮肤屏障,为中医"皮应大肠"理论和皮肤病从肠论治提供了实验依据.
北宋校正医书局校订刊行的《黄帝内经素问》《伤寒论》《金匮要略》《脉经》《千金要方》《千金翼方》《外台秘要》等重要医书,是研究医学问题的珍贵资料.本文根据宋校医书关于药秤的说明及其药用单位的使用情况,参考未经宋校《新雕孙真人千金方》相关材料,结合北宋校正医书局主要成员的身份特点、学术背景及其整理中医古籍的思想理念、方式方法等,考证出北宋校正医书局所校《金匮要略》《千金要方》《千金翼方》《外台秘要》等书采用小秤制,其量值等同于"百黍为铢制"的汉秤.
"喘而汗出""汗出而喘"分别见于《伤寒论》葛根芩连汤证与麻杏甘石汤证,被视为两方证的辨证要点之一.本文通过解读《伤寒论》原文两个方证,提出"而"有因果和强调之义,不仅突出了"汗出""喘"在辨病位、病因、病性、病势中的重要意义,而且反映了邪热在"皮""肺""肠"之间动态串扰势态,与现代医学基于皮肤、肺、肠疾病存在共病风险临床证据而提出的"肺—皮轴""肠—肺轴""肠—皮轴"不谋而合,为临床创新皮肤、肺、肠相关难治性疾病治法提供了思路.
伤寒大家刘渡舟教授从喘家圣药麻黄人手,结合《伤寒论》寒喘之小青龙汤证、热喘之麻杏石甘汤证,在应用甘露消毒丹加减治疗湿热咳喘的基础上,创造性地提出以麻杏苡甘汤治疗湿温羁肺作喘,开辟了临床辨治湿喘的新途径,使得"云龙三现"这一伟大奇观昭然成立,对辨治咳喘具有重要理论意义和临床价值.文章在介绍刘渡舟教授"云龙三现"理论辨治咳喘经验基础上,梳理出与其相应的效验方如宁嗽汤、止咳八味饮、麻黄连翘赤小豆汤等,以期能更好地继承和发扬仲景学术,启迪中医思路创新,指导临床实践.