摘要
目的 探究电针调控嘌呤能受体P2X7(P2X7 purinergic receptor, P2RX7)/NLR家族Pyrin域蛋白3(NLR family pyrin domain containing 3, NLRP3)信号通路对脓毒症急性肾损伤(sepsis associated acute kidney injury, SA-AKI)的保护效应及机制。方法 将6~8周龄C57BL/6J健康雄性小鼠随机分为空白组、模型组、电针组、P2RX7拮抗+模型组、P2RX7拮抗+模型+电针组;采用腹腔注射脂多糖(lipopolysaccharide, LPS)建立SA-AKI模型,LPS注射前1 h腹腔注射P2RX7拮抗剂A438079;LPS注射1.5 h后给予电针干预(10 Hz, 0.5 mA,30 min);造模后24 h内评估小鼠生存率,血液生化测定血清肌酐(serum creatinine, Scr)含量、ELISA检测血清及肾脏IL-1β和IL-18含量;HE染色观察肾脏组织病理学变化;实时荧光PCR和免疫荧光检测肾脏P2RX7、NLRP3表达水平。结果 与NS组小鼠存活率相比较,24 h内LPS组存活率降低至30%(P<0.05),而EA可将LPS小鼠存活率提升15%,但与LPS组相比较差异无统计学意义(P>0.05);电针治疗可改善小鼠肾脏组织病理损伤,降低SA-AKI的Scr水平(P<0.05),以及血清中炎症因子IL-1β和IL-18的含量(均P<0.000 1);电针减少肾脏组织中IL-1β(P<0.000 1)、IL-18(P<0.001)和P2RX7、NLRP3(均P<0.05)的表达水平。结论 电针改善SA-AKI的作用机制可能与抑制P2RX7/NLRP3信号通路、减轻全身炎症反应有关。
Objective To investigate the protective effects and mechanisms of electroacupuncture on the P2X7 purinergic receptor/NLRP3 signaling pathway in sepsis-associated acute kidney injury(SA-AKI).Methods Healthy male C57BL/6J mice,6-8 weeks old,were randomly assigned to the following groups:control,model,electroacupuncture,P2RX7 antagonist+model,and P2RX7 antagonist+model+electroacupuncture.The SA-AKI model was established by intraperitoneal injection of lipopolysaccharide(LPS).The P2RX7 antagonist A438079 was administered intraperitoneally 1 hour before LPS injection.Electroacupuncture(10 Hz,0.5 mA,30 min)was performed 1.5 hours after LPS injection.Mouse survival rates were assessed within 24 hours after modeling.Serum creatinine(Scr)levels were measured by blood biochemistry,IL-1βand IL-18 levels in serum and kidney tissues were measured with ELISA.Renal histopathological changes were observed by HE staining.Real-time fluorescent PCR and immunofluorescence assays were used to assess renal P2RX7 and NLRP3 expression levels.Results The 24-hour survival rate in the electroacupuncture group was 45%,a 15%improvement over the model group.Electroacupuncture treatment reduced renal histopathological damage,lowered Scr levels in SA-AKI(P<0.05),and decreased serum inflammatory mediators IL-1βand IL-18(both P<0.0001).Electroacupuncture also reduced renal tissue expression levels of IL-1β(P<0.0001),IL-18(P<0.001),P2RX7,and NLRP3(both P<0.05).Conclusion The mechanism by which electroacupuncture ameliorates SA-AKI may involve inhibition of the P2RX7/NLRP3 signaling pathway and attenuation of systemic inflammatory responses.
作者
王苗苗
赵晓晓
侯帅
肖欣怡
尹海燕
WANG Miaomiao;ZHAO Xiaoxiao;HOU Shuai;XIAO Xinyi;YIN Haiyan(Acupuncture and Tuina School,Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;Key Laboratory of Acupuncture for Senile Disease(Chengdu University of TCM),Ministry of Education,Chengdu 610075,China)
出处
《四川大学学报(医学版)》
北大核心
2026年第1期90-96,共7页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金项目(No.81774437、No.82274668、No.81973969)
四川省国际科技创新合作项目(No.2025YFHZ0121)资助。
