白芍总苷（TGP）通过抑制小鼠的炎症反应缓解干燥综合征。
Total glucosides of paeony (TGP) alleviates Sjogren's syndrome through inhibiting inflammatory responses in mice.
机构信息
State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
出版信息
Phytomedicine. 2020 Jun;71:153203. doi: 10.1016/j.phymed.2020.153203. Epub 2020 Mar 6.
BACKGROUND
Sjogren's syndrome (SS) is an inflammatory autoimmune disease whose etiology is complicated. Total glucosides of paeony (TGP) has a variety of pharmacological effects.
PURPOSE
To evaluate the therapeutic effects of TGP on SS in mice and anti-inflammatory mechanism.
STUDY DESIGN
SS animal model was developed from C57BL/6J mice through immunological induction (SS mice) and NOD/ShiltJNju (NOD) mice. Inflammatory cytokines and other related indicators were measured.
METHODS
TGP (720, 360, 180 mg/kg) was intragastrically administered for 6 or 16 weeks for SS mice and NOD mice, respectively. Average food and water intake, average body weight, saliva flow, submandibular gland (SMG) and spleen index, and SMG pathology were measured. ELISA was used to evaluate serum inflammatory cytokines in SS mice and autoantigens in NOD mice. Real-time PCR, Western blot and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA and protein expression of NOD mice.
RESULTS
Compared with SS mice, TGP treatment improved SMG pathological damage. TGP (720 mg/kg) treatment increased saliva flow, and reduced organ indexes and serum IL-6 and IFN-γ concentration. TGP (360 mg/kg) treatment decreased serum IFN-γ concentration. TGP (180 mg/kg) treatment for 6 weeks decreased average body weight. Compared with NOD mice, TGP treatment increased saliva flow from 9 to 15 weeks, decreased body weight, and alleviated pathological damage of SMG after 2 and 16 weeks. After 2 weeks of administration, TGP treatment inhibited serum concentration of SSB/La, SSA/Ro and α-fodrin, decreased TNF-α, IL-1β and IFN-γ in SMG, and down-regulated protein expressions of BAFF and IL-17A and mRNA expressions of BAFF, TNF-α, IL-17A, CXCL9 and CXCL13 in SMG. After 8 weeks of administration, TGP treatment decreased the concentration of α-fodrin in serum, TNF-α and IL-6 in SMG, and down-regulated mRNA expressions of IL-17A, TNF-α, CXCL9, CXCL13 and BAFF and protein expressions of IL-17A and BAFF in SMG. After 16 weeks of administration, TGP treatment reduced serum SSA/Ro, SSB/La and α-fodrin concentration, and decreased BAFF protein expression and TNF-α, CXCL9, CXCL13, IL-17A, and BAFF mRNA expressions.
CONCLUSION
TGP has a certain therapeutic effect on SS mice and NOD mice through inhibiting inflammatory responses.
背景
干燥综合征（SS）是一种炎症性自身免疫性疾病，其病因复杂。白芍总苷（TGP）具有多种药理作用。
目的
评价 TGP 对 SS 小鼠的治疗作用及抗炎机制。
研究设计
通过免疫诱导（SS 小鼠）和 NOD/ShiltJNju（NOD）小鼠建立 SS 动物模型。测定炎症细胞因子等相关指标。
方法
分别对 SS 小鼠和 NOD 小鼠给予 TGP（720、360、180mg/kg）灌胃 6 或 16 周。测量平均食物和水摄入量、平均体重、唾液流量、颌下腺（SMG）和脾脏指数以及 SMG 病理学。用 ELISA 法测定 SS 小鼠血清炎症细胞因子，NOD 小鼠血清自身抗原。用实时 PCR、Western blot 和 Luminex 液相悬浮芯片检测 NOD 小鼠 SMG 炎症细胞因子 mRNA 和蛋白表达。
结果
与 SS 小鼠相比，TGP 治疗改善了 SMG 病理损伤。TGP（720mg/kg）治疗增加了唾液流量，降低了器官指数和血清 IL-6 和 IFN-γ 浓度。TGP（360mg/kg）治疗降低了血清 IFN-γ 浓度。TGP（180mg/kg）治疗 6 周降低了平均体重。与 NOD 小鼠相比，TGP 治疗增加了 9 至 15 周的唾液流量，减轻了 2 周和 16 周 SMG 的体重和病理损伤。给药 2 周后，TGP 治疗抑制了血清 SSB/La、SSA/Ro 和 α- 纤维蛋白原的浓度，降低了 SMG 中的 TNF-α、IL-1β 和 IFN-γ，并下调了 SMG 中 BAFF 和 IL-17A 的蛋白表达以及 BAFF、TNF-α、IL-17A、CXCL9 和 CXCL13 的 mRNA 表达。给药 8 周后，TGP 治疗降低了血清 α-纤维蛋白原、SMG 中的 TNF-α 和 IL-6 的浓度，并下调了 SMG 中 IL-17A、TNF-α、CXCL9、CXCL13 和 BAFF 的 mRNA 表达以及 SMG 中 IL-17A 和 BAFF 的蛋白表达。给药 16 周后，TGP 治疗降低了血清 SSA/Ro、SSB/La 和 α-纤维蛋白原的浓度，降低了 BAFF 蛋白表达以及 TNF-α、CXCL9、CXCL13、IL-17A 和 BAFF 的 mRNA 表达。
结论
TGP 通过抑制炎症反应对 SS 小鼠和 NOD 小鼠具有一定的治疗作用。
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