白细胞介素17对大鼠高血压心力衰竭的影响及其机制分析  

Effect and mechanism of IL-17 on heart failure in hypertensive rats

作　　者：丁永刚[1] 马宏武 魏佳琪[3] 靳天楠 李依慧 王英子 Ding Yonggang;Ma Hongwu;Wei Jiaqi;Jin Tiannan;Li Yihui;Wang Yingzi(Outpatient Department,Lanzhou University Second Hospital,Lanzhou730030,Gansu Province,China)

机构地区：[1]兰州大学第二医院门诊部,730030 [2]兰州大学第二医院急诊科,730030 [3]兰州大学第二医院超声影像科,730030 [4]兰州大学第二医院神经外科,730030 [5]兰州大学第二医院中西医内分泌科,730030 [6]兰州市第一人民医院麻醉科

出　　处：《中华老年心脑血管病杂志》2024年第11期1343-1348,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：甘肃省自然科学基金(21JR7RA414)。

摘　　要：目的 基于核转录因子-κB(Nuclear factorκB,NF-κB)/肌浆网钙三磷酸腺苷酶2(sarco-endoplasmic reticulum adenosine triphosphatease 2S,SERCA2)信号通路探讨白细胞介素(interleukin, IL)17对大鼠高血压心力衰竭的影响及机制。方法 选择6~8周的SPF级雄性自发性高血压大鼠30只,分为对照组、模型组、磷酸缓冲盐(phosphate buffer salt, PBS)溶液注射组(PBS组)、IL-17蛋白注射组(IL-17组)和抗体IL-17注射组(IL-17+IgG组),每组6只,PBS组、IL-17组和IL-17+IgG组大鼠建立高血压心力衰竭模型,分别腹腔注射PBS、IL-17和特异性抗体(IL-17、IgG),检测IL-17、NF-κB、SERCA2水平。结果 与对照组比较,模型组和PBS组大鼠血清N末端B型钠尿肽前体(N-terminal pro-brain natriuretic peptide, NT-proBNP)、IL-17和心脏组织IL-17 mRNA、NF-κB蛋白水平明显升高,血管内皮生长因子(vascularendothlialgrowthfactor, VEGF),SERCA2蛋白明显降低(P<0.01)。与模型组比较,IL-17组血清NT-proBNP、IL-17和心脏组织IL-17 mRNA、NF-κB蛋白水平明显升高,VEGF,SERCA2蛋白水平明显降低(P<0.01)。IL-17+IgG组血清IL-17和心脏组织NF-κB蛋白水平明显低于模型组,差异有统计学意义(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P<0.01)。IL-17+IgG组血清NT-proBNP,IL-17和心脏组织IL-17 mRNA、NF-κB蛋白水平明显低于IL-17组,VEGF、SERCA2蛋白水平明显高于IL-17组,差异有统计学意义(P<0.01)。IL-17+IgG组大鼠心率、收缩压、舒张末期室间隔厚度、左心室舒张末期后壁厚度、左心室舒张末期内径、左心室收缩末期内径明显低于模型组和IL-17组,左心室短轴缩短率明显高于模型组和IL-17组(P<0.01)。IL-17+IgG组大鼠左心室射血分数明显高于IL-17组[(70.81±6.50)%vs(62.77±5.43)%,P<0.01]。结论 IL-17、NF-κB、SERCA2信号通路参与调节高血压心力衰竭后的炎性反应,且抑制IL-17后可有效改善高血压心力衰竭造成的心功能损伤。Objective To investigate the effect and mechanism of IL-17 on heart failure(HF)in hypertensive rats based on NF-κB/sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)signaling pathway.Methods Thirty SPF male spontaneously hypertensive rats(SHR)aged 6-8 weeks were divided into control group,model group,phosphate buffer salt(PBS)solution injection group(PBS group),IL-17 protein injection group(IL-17 group)and IL-17 and antibody injection group(IL-17+IgG group),with 6 animals in each group.Hypertensive HF model was established,and corresponding agents were applied to the PBS group,IL-17 group and IL-17+IgG group intraperitoneally,respectively.The role of IL-17,NF-κB and SERCA2 in hypertensive HF was studied with HE staining,immunohistochemical assay,Western blotting,RT-qPCR and ELISA.Results Significantly higher serum levels of NT-proBNP and IL-17,enhanced myocardial expression of IL-17 mRNA and NF-κB protein,lower serum VEGF level,and down-regulated protein level of SERCA2 in heart tissue were observed in the model group and the PBS group when compared with the control group(P<0.01).The IL-17 group had obviously higher serum NT-proBNP and IL-17 levels and myocardial expression of IL-17 mRNA and NF-κB protein,and reduced serum VEGF level and SERCA2 protein level in heart tissue than the model group(P<0.01).IL-17+IgG treatment resulted in notably lower serum IL-17 level and myocardial NF-κB protein level when compared with those of model group(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P<0.01),and also resulted in remarkably reduced serum levels of NT-proBNP and IL-17 and myocardial expression of IL-17 mRNA and NF-κB protein but increased serum VEGF level and SERCA2 protein level in heart tissue when compared with the IL-17 group(P<0.01).The heart rate,SBP,IVSd,LVPWd,LVEDD and LVESD were significantly lower,while LVFS was notably higher in the IL-17+IgG group than the model group and IL-17 group(P<0.01).The IL-17+IgG group had obviously higher LVEF than the IL-17 group[(70.81±6.50)%vs(62.77±5.43)%,P<

关 键 词：白细胞介素17 肌浆网钙转运ATP酶类 NF-ΚB 大鼠 高血压心力衰竭模型 

分 类 号：R544.1[医药卫生—心血管疾病] R541.6[医药卫生—内科学]