首页|防己黄芪汤通过抑制Notch1通路减轻大鼠胶原诱导性关节炎的机制

防己黄芪汤通过抑制Notch1通路减轻大鼠胶原诱导性关节炎的机制

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目的:探讨防己黄芪汤(FHD)通过Notch1通路减轻大鼠胶原诱导性关节炎(CIA)大鼠中的机制.方法:采用牛Ⅱ型胶原溶液和完全弗氏佐剂/不完全弗氏佐剂建立CIA模型,FHD低、中、高剂量组分别进行2.2、4.4、8.8 g·kg-1·d-1的FHD干预,每周检测关节炎评分和足关节肿胀度.Masson染色观察关节组织病理形态;ELISA检测大鼠血清白细胞介素(IL)-iβ、IL-4、IL-10和IL-17表达;qRT-PCR检测关节和脾脏Notch1、Jagged1、Hes1 mRNA水平,Western Blot检测关节和脾脏Notch1、Jagged1、Hes1 和Notch胞内结构域(NICD)蛋白,免疫组化评估关节Notch1、Jagged1、Hes1和NICD的阳性面积.结果:与模型组比较,FHD中、高剂量组大鼠关节炎评分及足关节肿胀度降低(P<0.01),关节破坏减轻,血清促炎细胞因子IL-1β和IL-17降低(P<0.01),抗炎细胞因子IL-4和IL-10升高(P<0.01),关节和脾脏Notch1、Jagged1、Hes1蛋白和mRNA及NICD蛋白表达降低(P<0.01),关节Notch1、Jagged1、Hes1和NICD的阳性面积减少(P<0.01,P<0.05).结论:FHD通过抑制Notch1信号通路,恢复炎症细胞因子网络平衡,发挥抗关节炎的作用.
Mechanism of Fangji Huangqi Decoction on alleviating collagen-induced arthritis in rats by inhibiting the Notch1 pathway
Objective:To explore the mechanism of Fangji Huangqi Decoction(FHD)on alleviating collagen-induced arthritis(CIA)in rats through Notch1 pathway.Methods:The rat model of collagen-induced arthritis(CIA)was established by injection of type Ⅱ bovine collagen solution mixed with complete/incomplete Freund's adjuvant.The low,middle and high dose FHD groups were treated with 2.2,4.4,8.8 g·kg-1·d-1 FHD respectively.The arthritis score and paw swelling were measured every week.The pathological morphology of joint tissue was observed by Masson staining,the expression of interleukin(IL)-1 β,IL-4,IL-10 and IL-17 in serum was detected by ELISA.The mRNA levels of Notch1,Jagged1 and Hes1 in joint and spleen were detected by qRT-PCR,Notch1,Jagged1,Hes1 and Notch intracellular domain(NICD)protein in joint and spleen were detected by Western Blot,and the positive areas of Notch1,Jagged1,Hes1 and NICD in joint were evaluated by immunohistochemistry.Results:Compared with CIA group,in the middle and high dose FHD groups,arthritis scores and foot paw swelling were decreased(P<0.01),joint destruction reduced,IL-1 β and IL-17 were decreased(P<0.01),and IL-4 and IL-10 were increased(P<0.01),the protein and mRNA expressions of Notch1,Jagged1,Hes1,and the protein expression of NICD in the spleen and joints were down-regulation(P<0.01),the positive area of Notch1,Jagged1,Hes1 and NICD were decreased(P<0.01,P<0.05).Conc1usion:FHD restore the balance of inflammatory cytokine network and play an anti-arthritis effect by inhibiting Notchl signal pathway.

Rheumatoid arthritis(RA)Fangji Huangqi DecoctionCollagen-induced arthritis(CIA)Inflammatory cytokineNotch1 signaling pathway

高玉亭、赵彩虹、肖冰、刘进、郝慧琴

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山西中医药大学基础医学院,晋中 030619

类风湿关节炎 防己黄芪汤 胶原诱导性关节炎 炎症细胞因子 Notch1信号通路

山西省卫健委科研项目山西中医药大学科技创新能力培育计划山西中医药大学科技创新能力培育计划山西省医学重点科研项目引导性科技专项中央引导地方科技发展资金项目

20210422021PY-JC-082023PY-YS-012021XM52YDZJSX2021A040

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(8)