杨梅苷对细菌性骨髓炎大鼠骨缺损的改善作用  

Improvement effect of myricitrin on bone defect in rats with bacterial osteomyelitis

作　　者：阮峻[1] 李炫莹 陈国材 RUAN Jun;LI Xuanying;CHEN Guocai(Department of Orthopaedics,Foshan Hospital of Traditional Chinese Medicine,Foshan 528000,China)

机构地区：[1]佛山市中医院骨伤科,528000

出　　处：《天津医药》2023年第12期1344-1348,共5页Tianjin Medical Journal

基　　金：2021年度广东省基础与应用基础研究基金联合基金(2021A1515110142)。

摘　　要：目的 探究杨梅苷通过血管内皮生长因子A(VEGFA)/基质细胞衍生因子-1(SDF-1)/C-X-C型趋化因子受体4(CXCR4)通路对细菌性骨髓炎(OM)大鼠骨缺损的改善作用。方法 将大鼠按随机数字表法分为假手术组、OM组、杨梅苷组[50 mg/(kg·d)杨梅苷]、PX-478组[25 mg/(kg·d)VEGFA/SDF-1/CXCR4信号通路抑制剂PX-478]、杨梅苷+PX-478组[50 mg/(kg·d)杨梅苷和25 mg/(kg·d)PX-478],每组18只。采用双侧胫骨近端骨缺损来构建细菌性OM大鼠模型。连续治疗12周后,观察大鼠创口愈合程度,测量大鼠肛温;酶联免疫吸附试验(ELISA)法检测血清炎性因子白细胞介素(IL)-6、IL-1β、IL-17以及骨代谢指标骨碱性磷酸酶(BALP)、骨钙素(BGP)、Ⅰ型胶原C端肽(CTX-Ⅰ)水平;检测病灶周围组织细菌负荷情况;HE染色检测大鼠病灶周围组织病理变化;免疫荧光染色检测CD31阳性表达;Western blot检测VEGFA/SDF-1/CXCR4信号通路相关蛋白表达。结果 与假手术组相比,OM组达到甲级创口愈合程度的大鼠比例,BALP、BGP水平,CD31阳性区域面积,VEGFA、SDF-1、CXCR4蛋白水平下降(P<0.005或P<0.05);肛温,细菌负荷,血清IL-6、IL-1β、IL-17、CTX-Ⅰ水平升高(P<0.05)。与OM组相比,杨梅苷组BALP、BGP水平,CD31阳性区域面积,VEGFA、SDF-1、CXCR4蛋白水平升高;肛温,细菌负荷,血清IL-6、IL-1β、IL-17水平,CTX-Ⅰ水平降低(P<0.05);而PX-478组结果趋势相反。PX-478逆转了杨梅苷对细菌性OM大鼠骨缺损的改善作用。结论 杨梅苷可能通过激活VEGFA/SDF-1/CXCR4信号通路改善OM大鼠骨缺损。Objective To explore the improvement effect of myricitrin on bone defect in rats with bacterial osteomyelitis(OM)through vascular endothelial growth factor A(VEGFA)/stromal cell-derived factor(SDF-1)/C-X-C chemokine receptor 4(CXCR4)pathway.Methods Rats were randomly divided into the sham operation group,the OM group,the myricitrin group[50 mg/(kg•d)],PX-478 group[25 mg/(kg•d)VEGFA/SDF-1/CXCR4 signaling pathway inhibitor PX-478],and the myricitrin+PX-478 group[50 mg/(kg•d)myricitrin and 25 mg/(kg•d)PX-478],18 mice per group.Bilateral proximal tibia bone defects were used to construct bacterial OM rat model.After 12 weeks of continuous treatment,the wound healing degree of rats was observed,and anal temperature of rats was measured.The serum inflammatory factors interleukin(IL)-6,IL-1β,IL-17 and bone metabolism indexes bone alkaline phosphatase(BALP),osteocalcin(BGP)and Cterminal telopeptide of typeⅠcollagen(CTX-Ⅰ)were measured by enzyma-linked immunosorbent assay(ELISA).The bacterial load of tissue around the lesion was detected.HE staining was used to detect the pathological changes of the tissue around lesions.The expression of CD31 was detected by immunofluorescence staining.Western blot assay was used to detect the expression of VEGFA/SDF-1/CXCR4 signal pathway related proteins.Results Compared with the sham operation group,the number of rats with grade A wound healing,BALP and BGP levels,CD31 positive area,VEGFA,SDF-1 and CXCR4 protein levels were decreased in the OM group(P<0.005 or P<0.05),and the anal temperature,bacterial load,IL-6,IL-1β,IL-17 and CTX-Ⅰlevels were increased(P<0.05).Compared with the OM group,the BALP and BGP levels,CD31 positive area,VEGFA,SDF-1 and CXCR4 protein levels were increased,and the anal temperature,bacterial load,IL-6,IL-1β,IL-17 and CTX-Ⅰlevels were decreased in the myricitrin group(P<0.05).Results of PX-478 group showed the opposite trend.PX-478 reversed the effect of myricitrin on the improvement of bone defects in bacterial OM rats.Conclusion Myricitrin

关 键 词：骨髓炎 血管内皮生长因子A 趋化因子CXCL12 受体 CXCR4 杨梅苷 骨缺损 血管生成 

分 类 号：R681.21[医药卫生—骨科学]