基于CXCL8-CXCR1/2轴探讨苗药验方“四大血”对CIA大鼠的作用机制  

Exploring the effect of Miao formula"sidaxue"on fats with CIA based on CXCL8-CXCR1/2 axis and its mechanism

作　　者：张丹 翁骏宁 石桂霖 奉静雨 何远 吴宁 孙见飞 吴遵秋 ZHANG Dan;WENG Junning;SHI Guilin;FENG Jingyu;HE Yuan;WU Ning;SUN Jianfei;WU Zunqiu(School of Clinical Medicine,Guizhou Medical University,Guiyang 550004,Guizhou,China;Chemistry and Biochemistry Laboratory,School of Basic Medical Science,Guizhou Medical University,Guiyang 550025,Guizhou,China)

机构地区：[1]贵州医科大学临床医学院,贵州贵阳550004 [2]贵州医科大学基础医学院化学与生物化学实验室,贵州贵阳550025

出　　处：《贵州医科大学学报》2025年第4期513-519,共7页Journal of Guizhou Medical University

摘　　要：目的探究苗药验方“四大血”(sidaxue,SX)通过CXC趋化因子配体8(CXC chemokine ligand 8,CXCL8)-G蛋白偶联受体C-X-C趋化因子受体1型(CXC chemokine receptor1,CXCR1)/CXCR2轴对胶原诱导型类风湿关节炎(collegen induced arthritis in rat,CIA)大鼠的作用及其机制。方法42只SD大鼠采用随机数字表法分为空白对照组(Nor组)、模型对照组(Mod组)、阳性对照组(GTW组,40 g/kg)、SX高剂量组(40 g/kg)、SX中剂量组(20 g/kg)、SX低剂量组(10 g/kg);采用HE染色观察滑膜组织病理形态学变化,采用Western blot法检测膝踝关节组织CXCR1、CXCR2、血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白表达,采用Real-time PCR法检测滑膜组织的CXCL8、CXCR1、CXCR2 mRNA的表达,采用ELSIA法检测血清中CXCL8含量。结果给药21 d时,膝踝关节滑膜组织病理学切片结果显示,与Mod组相比,SX组大鼠关节内滑膜组织炎细胞浸润、软骨破坏、滑膜增生与绒毛样突起均有减轻,其中SX 40 g/kg、SX 20 g/kg组更明显;与Mod组相比,GTW组和SX 40 g/kg组膝踝关节组织中CXCR1、CXCR2、VEGF蛋白表达水平均下降(P<0.01);与Mod组相比,GTW组和SX 40 g/kg组滑膜组织中CXCL8、CXCR1、CXCR2 mRNA表达水平均下降(P<0.01);与Mod组相比,大鼠血清中CXCL8的表达量降低(P<0.05)。结论SX能拮抗CIA病情的发展,其作用机制可能与SX抑制CXCL8-CXCR1/2轴活化有关。Objective To explore the effect of Sidaxue(SX),a Miao formula on rats with collagen-induced rheumatoid arthritis(CIA)via CXC chemokine ligand 8(CXCL8)-CXC chemokine receptor1/2(CXCR1/2)axis and its mechanism.Methods A total of 42 SD rats were randomly divided into blank control(Nor group),model control(Mod group),positive control(GTW group,40 g/kg),SX high-dose group(40 g/kg),SX medium-dose group(20 g/kg)and SX low-dose group(10 g/kg).HE staining was applied to observe pathomorphological change in synovial tissue.Western blot was performed to detect the protein expressions of CXCR1,CXCR2,and vascular endothelial growth factor(VEGF)in knee and ankle joint tissues.mRNA expressions of CXCL8,CXCR1 and CXCR2 in synovial tissue was detected by real-time fluorescence quantitative RT-PCR.ELSIA was used to detect serum CXCL8 content.Results At 21 days post-administration,histopathological examination of synovial tissues from knee and ankle joints showed that when compared to Mod group,SX group exhibited reduced inflammatory cell infiltration,cartilage destruction,synovial hyperplasia and villous protrusions,with SX 40 g/kg and SX 20 g/kg groups being more pronounced.When compared to Mod group,both GTW and SX 40 g/kg groups showed the decreased protein expression levels of CXCR1,CXCR2 and VEGF in knee and ankle joint tissues(P<0.01).When compared to Mod group,the mRNA levels of CXCL8,CXCR1,and CXCR2 in synovial tissue were downregulated in GTW and SX 40 g/kg groups(P<0.01).When compared to Mod group,rat serum CXCL8 expression levels were decreased(P<0.05).Conclusion SX can antagonize CIA progression,and its mechanism may be associated with SX-mediated suppression on the activation of CXCL8-CXCR1/2 axis.

关 键 词：关节炎 类风湿 苗药“四大血” CXCL8-CXCR1/2轴 血管内皮生长因子 

分 类 号：R34[医药卫生—基础医学] R593.22