右美托咪定通过a7nAChR依赖途径缓解脂多糖诱导的小鼠脓毒血症模型肾损伤机制  

Mechanism of Dexmedetomidine Alleviating Lipopolysaccharide-induced Renal Injury in a Mouse Model of Sepsis through a7nAChR-dependent Pathway

作　　者：闫振亚 邓友明[2] 朱林夕 YAN zhenya;DENG youming;ZHU linxi(Department of Anesthesiology,Maternal and Child Health Hospital of Pingdingshan,Henan Pingdingshan 467000,China;Department of anesthesiology,nanjing second hospital,Jiangsu Nanjing 210003,China.)

机构地区：[1]河南省平顶山市妇幼保健院麻醉科,河南平顶山467000 [2]南京市第二医院麻醉科,江苏南京2210003

出　　处：《实验与检验医学》2022年第4期415-419,共5页Experimental and Laboratory Medicine

摘　　要：目的 观察右美托咪定通过a7nAChR依赖途径缓解脂多糖诱导的小鼠脓毒血症模型肾损伤的保护作用,并对其机制进行初步探讨。方法 将实验小鼠随机分为空白对照组(C组)、LPS诱导急性肾损伤组(AKI组)、右美托咪定防护组(D1组)和右美托咪定+LPS+a7nAChR抑制剂组(D2组),每组10只。建立内毒素血症小鼠模型,检测血清肌酐(SCr)和血清尿素氮(Blood urea nitrogen,BUN)的变化;HE检测肾脏病理组织学变化,Western blotting和实时PCR检测大鼠肾脏中a7nAChR蛋白及mRNA表达。通过酶联免疫吸附测定法(ELISA)分析各组大鼠肾组织中促炎因子TNF-α、IL-1β、IL-6的表达。结果 与C组相比,AKI组小鼠肾脏损伤明显,血清中SCr、BUN水平升高,肾脏病理组织学变化更明显;而在建模前给予右美托嘧啶可以改善AKI,降低血清中SCr、BUN水平,提升a7nAChR蛋白及mRNA表达;给予a7nAChR抑制剂后,右美托咪定对AKI的保护作用受到抑制。与C组SCr和BUN含量相比,AKI组TNF-α、IL-1β、IL-6含量升高,差异有统计学意义(P<0.05);与AKI组相比,D1组TNF-α、IL-1β、IL-6含量降低,差异有统计学意义(P<0.05);与D1组相比,D2组TNF-α、IL-1β、IL-6含量升高,差异有统计学意义(P<0.05)。结论 右美托嘧啶对脂多糖导致的肾损伤有保护作用,其机制可能与a7nAChR依赖途径有关。Objective To observe the efect of dexmedetomidine on acute kidney injury induced by lipopolysaccharide and discuss its mechanism.Methods The mice were randomly divided into blank control group(Group C),LPS induced acute kidney injury group(AKI group),dexmedetomidine protection group(D1 group)and dexmedetomidine+LPS+a7nAChR inhibitor group(D2 group),with 10 mice in each group.The changes of serum creatinine(SCR)and urea nitrogen(BUN)were detected.HE staining was used to detect the pathological changes of kidney.Western blotting and real-time PCR were used to detect the expression of a7nAChR protein and mRNA.The expression of proinflammatory factors TNF-α,IL-1βand IL-6 in renal tissue of rats in each group was analyzed by enzyme linked immunosorbent assay(ELISA).Results Compared with group C,kidney injury was obvious in AKI group,SCr and BUN levels in serum were increased,and renal histopathological changes were more obvious in AKI group.However,dexmedetomidine can improve AKI,reduce the levels of SCr and BUN in serum,and increase the expression of a7nAChR protein and mRNA.After administration of a7nAChR inhibitor,the protective effect of dexmedetomidine on AKI was inhibited.Compared with the levels of SCr and BUN in group C,the levels of TNF-α,IL-1βand IL-6 in AKI group were significantly increased(P<0.05).Compared with AKI group,the contents of TNF-α,IL-1βand IL-6 in D1 group were significantly lower(P<0.05).Compared with group D1,the levels of TNF-α,IL-1βand IL-6 in group D2 were significantly higher(P<0.05).Conclusion Dexmedetomidine exhibited a protective effect against LPS-induced AKI by increasing the activation of a7nAChR pathway.

关 键 词：右美托咪定 a7nAChR依赖途径 脂多糖 肾损伤 

分 类 号：R691.6[医药卫生—泌尿科学]