C-X-C趋化因子受体4增强Toll样受体2在肺炎衣原体感染促进动脉粥样硬化病变形成中的作用  

C-X-C motif chemokine receptor 4 enhances the role of Toll-like receptor 2 in the formation of atherosclerotic lesions promoted by Chlamydia pneumoniae infection

作　　者：张琪 张利军 张雨珂 李忆 赵茜 苗国琳 王蓓蓓 张丽莙 ZHANG Qi;ZHANG Lijun;ZHANG Yuke;LI Yi;ZHAO Xi;MIAO Guolin;WANG Beibei;ZHANG Lijun(Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学基础医学院生理学与病理生理学系,天津市300070

出　　处：《中国动脉硬化杂志》2024年第2期102-108,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(81470551、82070452)。

摘　　要：[目的]探究C-X-C趋化因子受体4(CXCR4)在肺炎衣原体(C.pn)感染促进动脉粥样硬化(As)病变形成中的作用。[方法]以高脂饮食为基础,建立C.pn感染诱导ApoE^(-/-)、ApoE^(-/-)+Toll样受体2(TLR2)^(-/-)、ApoE^(-/-)+TLR2^(-/-)+AMD3100小鼠As模型,ELISA检测ApoE^(-/-)小鼠血清C.pn IgG、IgM抗体水平,PCR检测肺组织C.pn特异性DNA,油红O染色和HE染色观察主动脉及主动脉根部脂质沉积和As病变面积,比色法测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)和高密度脂蛋白胆固醇(HDLC)水平,ELISA检测血清白细胞介素1β(IL-1β)和白细胞介素6(IL-6)含量。[结果]ApoE^(-/-)小鼠C.pn感染模型成功建立。与对照组相比,C.pn感染后ApoE^(-/-)小鼠主动脉及主动脉根部脂质沉积量增加89.08%和71.83%,As病变面积增加34.12%(均P<0.05);与C.pn感染组相比,TLR2^(-/-)+C.pn感染组主动脉及主动脉根部脂质沉积量减少46.16%和75.73%,As病变面积减少63.37%(均P<0.05);与TLR2^(-/-)+C.pn感染组相比,TLR2^(-/-)+AMD3100+C.pn感染组主动脉及主动脉根部脂质沉积量减少26.19%和56.94%,As病变面积则减少22.24%(均P<0.05)。与对照组相比,C.pn感染后血清TC、TG和LDLC水平分别升高0.62倍、1.43倍和1.34倍,血清IL-1β和IL-6含量分别增加4.10倍和6.00倍(均P<0.05);与C.pn感染组相比,TLR2^(-/-)+C.pn感染组血清TC、TG和LDLC水平分别降低56.96%、50.41%和66.64%,血清IL-1β和IL-6含量分别减少66.72%和69.54%(均P<0.05);与TLR2^(-/-)+C.pn感染组相比,TLR2^(-/-)+AMD3100+C.pn感染组血清TC、TG和LDLC水平分别降低52.18%、58.56%和60.61%,血清IL-1β和IL-6含量分别减少28.84%和43.18%(均P<0.05)。[结论]CXCR4可增强TLR2在升高血脂水平及炎症因子含量中的作用,进而参与C.pn感染诱导的As病变形成。Aim To explore the role of C-X-C motif chemokine receptor 4(CXCR4)in the formation of atherosclerosis(As)induced by Chlamydia pneumoniae(C.pn)infection.Methods The As model in mice of ApoE^(-/-),ApoE^(-/-)+TLR2^(-/-)and ApoE^(-/-)+Toll-like receptor 2(TLR2)^(-/-)+AMD3100 induced by C.pn infection was established on the basis of high fat diet.C.pn IgG and IgM antibody levels were detected by ELISA,and C.pn specific DNA was detected by PCR.Lipid deposition and As lesion area in aorta and aortic root were observed by oil red O and HE staining.Serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDLC)and high density lipoprotein cholesterol(HDLC)were analyzed by colorimetry,and ELISA was used to measure the contents of serum interleukin-1β(IL-1β)and interleukin-6(IL-6).Results The ApoE^(-/-)mice model of C.pn infection was established successfully.Compared with the control group,lipid deposition in aorta and aortic root of ApoE^(-/-)mice increased by 89.08%and 71.83%,and As lesion area increased by 34.12%after C.pn infection(all P<0.05).Compared with the C.pn infection group,lipid deposition in aorta and aortic root reduced by 46.16%and 75.73%,and the lesion area of As decreased by 63.37%in the TLR2^(-/-)+C.pn infection group(all P<0.05).Compared with the TLR2^(-/-)+C.pn infection group,lipid deposition in aorta and aortic root decreased by 26.19%and 56.94%,and the lesion area of As decreased by 22.24%in the TLR2^(-/-)+AMD3100+C.pn infection group(all P<0.05).Compared with the control group,serum levels of TC,TG and LDLC increased by 0.62 times,1.43 times and 1.34 times after C.pn infection,respectively,while serum contents of IL-1βand IL-6 increased by 4.10 times and 6.00 times,respectively(all P<0.05).Compared with the C.pn infection group,serum levels of TC,TG and LDLC in the TLR2^(-/-)+C.pn infection group decreased by 56.96%,50.41%and 66.64%,and serum contents of IL-1βand IL-6 also decreased by 66.72%and 69.54%respectively(all P<0.05).Compared with the TLR2^(-/-)+C.pn in

关 键 词：动脉粥样硬化 C-X-C趋化因子受体4 TOLL样受体2 肺炎衣原体 

分 类 号：R363[医药卫生—病理学] R5[医药卫生—基础医学]