Abstract：
Sjögren\'s syndrome (SS) is the second most common autoimmune rheumatism. Huoxue Jiedu Recipe (HXJDR) is a kind of traditional Chinese medicine with a variety of pharmacological functions; however, its biological function in SS has not been studied yet. Peripheral blood mononuclear cells (PBMCs) and serum samples were isolated from healthy controls and patients with SS. NOD/Ltj mice were used for developing the SS mouse model. The levels of inflammatory cytokines and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers as well as dynamin-related protein 1 (Drp1) were determined by ELISA, quantitative real-time PCR, and western blot analysis, respectively. Hematoxylin and eosin and TUNEL staining detected the pathological damage. A transmission electron microscope was used to observe the mitochondrial microstructure. Inflammatory cytokines IL-18, IL-1β, B-cell activating factor (BAFF), BAFF-receptor (BAFF-R), IL-6, and TNF-α in serum samples and NLRP3 inflammasome-related makers (NLRP3, cysteinyl aspartate-specific proteinase 1 [caspase-1], apoptosis-associated speck-like protein containing a caspase-1 recruitment domain [ASC], IL-1β) in PBMCs were greatly upregulated in patients with SS. Furthermore, cytoplasmic phosphorylation of Drp1 and mitochondrial Drp1 level were significantly increased in PBMCs, while mitochondrial swelling and fuzzy inner ridge were observed in PBMCs of patients with SS, suggesting increased mitochondrial fission. Compared with control mice, SS mice showed decreased salivary flow rate, increased submandibular gland index, and more severe inflammatory infiltration and damage as well as mitochondrial fission in submandibular gland tissues. After HXJDR administration, these effects were significantly reversed. HXJDR treatment could alleviate the inflammatory infiltration and pathological damage in submandibular glands of SS mice by inhibiting Drp-1-dependent mitochondrial fission.
摘要：
干燥综合征（SS）是第二常见的自身免疫性风湿病。活血解毒方是一种具有多种药理作用的中药,其在SS中的生物学功能尚未被研究。从健康对照和SS患者中分离外周血单核细胞(PBMC)和血清样品。NOD/Ltj小鼠用于开发SS小鼠模型。通过ELISA测定炎性细胞因子和NOD样受体家族pyrin结构域包含3（NLRP3）炎症小体相关标志物以及动力蛋白相关蛋白1（Drp1）的水平，实时定量PCR,和蛋白质印迹分析，分别。苏木素、伊红和TUNEL染色检测病理毁伤。采用透射电镜观察线粒体微观结构。炎症细胞因子IL-18,IL-1β,B细胞活化因子(BAFF),BAFF受体(BAFF-R),血清样品中的IL-6和TNF-α以及NLRP3炎性体相关标记（NLRP3，半胱氨酰天冬氨酸特异性蛋白酶1[caspase-1]，含有caspase-1募集结构域[ASC]的凋亡相关斑点样蛋白，SS患者PBMC中的IL-1β）大幅上调。此外，PBMC中Drp1的细胞质磷酸化和线粒体Drp1水平显著增加，而在SS患者的PBMC中观察到线粒体肿胀和模糊的内脊，表明线粒体裂变增加。与对照小鼠相比，SS小鼠显示唾液流速降低，颌下腺指数增加，下颌下腺组织中更严重的炎症浸润和损伤以及线粒体裂变。在HXJDR管理之后，这些影响显著逆转。HXJDR治疗可通过抑制Drp-1依赖的线粒体裂变减轻SS小鼠下颌下腺的炎性浸润和病理损伤。
