苯磺酸芍药苷通过调控颌下腺GRK2-JAK1-STAT1/2信号通路治疗抗原诱导型小鼠干燥综合征  

Paeoniflorin besylate relieves mice with antigen-induced experimental Sjögren's syndrome by regulating GRK2-JAK1-STAT1/2 signaling pathway

作　　者：吴华勋[1] 陈晓芸 刘琪 张巧琳 黄磊 周彤彤 魏伟[1] WU Hua-xun;CHEN Xiao-yun;LIU Qi;ZHANG Qiao-lin;HUANG Lei;ZHOU Tong-tong;WEI Wei(Institute of Clinical Pharmacology, Anhui Medical University, Key Lab of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,抗炎免疫药物安徽省协同创新中心,安徽合肥230032

出　　处：《中国药理学通报》2021年第2期245-250,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81973332,81673444);安徽高校自然科学研究重点项目(No KJ2018A0166);高校优秀青年人才支持计划重点项目(No gxyqZD2018023)。

摘　　要：目的观察苯磺酸芍药苷(代号CP-25)对实验性干燥综合征(experimental Sjögren's Syndrome,ESS)小鼠模型的作用,探讨其作用机制是否通过调节GRK2与JAK1的结合,抑制JAK1-STAT1/2-CXCL13信号通路而发挥作用。方法建立颌下腺蛋白诱导的ESS小鼠模型,分为正常组、模型组、浓度分别为35、70 mg·kg^-1的CP-25组、浓度为80 mg·kg^-1的羟氯喹组;检测小鼠唾液流率;ESS小鼠颌下腺做病理切片以观察淋巴细胞浸润情况;小鼠颌下腺中p-JAK1、p-STAT1、p-STAT2蛋白水平用Western blot测定;小鼠颌下腺中CXCL13的表达情况采用免疫组化法检测;免疫荧光及CO-IP法检测GRK2与JAK1的结合情况。结果ESS小鼠唾液流率较正常组降低,颌下腺病理切片中淋巴细胞明显浸润,CXCL13蛋白表达升高,活化了JAK1-STAT1/2信号;CP-25能明显增加ESS小鼠唾液流率,降低淋巴细胞浸润,改善病理的异常表现,阻断JAK1-STAT1/2及CXCL13的表达;CP-25能明显促进GRK2与JAK1的结合。结论CP-25可能通过促进GRK2与JAK1的结合,进而抑制JAK1-STAT1/2-CXCL13信号的激活,减少颌下腺淋巴细胞浸润,提高唾液流率,对ESS小鼠产生治疗作用。Aim To observe the effect of CP-25 on the ESS mouse model and establish whether its effect is through regulating the binding of GRK2 to JAK1 and inhibiting the JAK1-STAT1/2-CXCL13 signaling pathway.Method We established ESS mouse model induced by SG protein,established into normal group,model group,CP-25 group with concentration of 35 mg·kg^-1,70 mg·kg^-1,and HCQ group with concentration of 80 mg·kg^-1.Mouse saliva flow was measured.The infiltration of lymphocyte in SG was observed by HE staining.The expression of p-JAK1,p-STAT1 and p-STAT2 in submandibular gland tissue was detected by Western blot.The level of CXCL13 in SG of mice was tested by IHC.GRK2 and JAK1 binding was determined by immunofluorescence and CO-IP.Results Compared with normal group,the saliva flow rate of ESS mice was low and lymphocytes were significantly infiltrated in the submandibular gland pathological sections.The CXCL13 protein level was highly expressed,which activated the JAK1-STAT1/2 signal.CP-25 significantly increased the salivary flow rate in ESS mice,reduced lymphocyte infiltration,improved pathological abnormalities,and inhibited the expression of JAK1-STAT1/2 signaling and CXCL13.CP-25 significantly promoted the binding of GRK2 to JAK1.Conclusions CP-25 may inhibit the binding of GRK2 to JAK1,and then inhibit the activation of JAK1-STAT1/2-CXCL13 signaling pathway,improve the abnormal pathological manifestations of lymphocyte infiltration in submandibular gland,and improve the rate of saliva flow.CP-25 plays a therapeutic role in ESS mice.

关 键 词：干燥综合征 苯磺酸芍药苷 GRK2 JAK STAT 颌下腺 

分 类 号：R-332[医药卫生—中药学] R285.5[医药卫生—中医学]