盐酸小檗胺对脓毒症急性肾损伤小鼠的保护机制研究  

The Effect of Berbamine Hydrochloride on Mice with Septic Acute Kidney Injury

作　　者：孙珊珊 何昂 马谣谣 黄翠萍 SUN Shan-shan;HE Ang;HUANG Cui-ping(School of Pharmacy,Xianning Medical College,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院医学部药学院,湖北咸宁437100 [2]湖北科技学院第二附属医院

出　　处：《湖北科技学院学报（医学版）》2024年第6期477-481,共5页Journal of Hubei University of Science and Technology(Medical Sciences)

摘　　要：目的探究盐酸小檗胺对脓毒症引起的急性肾损伤(AKI)小鼠模型的保护效应及其可能机制。方法选用C57小鼠24只,随机分为4组,每组6只,分别为空白对照(CON)组、模型(LPS)组、盐酸小檗胺治疗(LPS+BBM)组及盐酸小檗胺对照(BBM)组。通过腹腔注射脂多糖(LPS)建立脓毒症急性肾损伤模型。采用HE染色法观察各组小鼠肾脏组织的病理学变化,通过免疫荧光法检测肾组织中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)及核因子κB p65(NF-κB p65)蛋白的表达,使用丙二醛(MDA)与超氧化物歧化酶(SOD)试剂盒测定SOD活性和MDA含量,通过Western blot方法检测肾组织中核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)及磷酸化NF-κB(p-NF-κB)蛋白的表达水平。结果与CON组相比,LPS组小鼠肾脏出现明显的水肿、变性和炎性细胞浸润,肾损伤评分显著增加,肾组织中TNF-α、IL-6、IL-1β及NF-κB p65蛋白的表达及p-NF-κB蛋白水平显著上升,而Nrf2及HO-1表达降低,SOD活性减弱,MDA含量增加(P均<0.05)。相较于LPS组,LPS+BBM组小鼠肾组织炎症浸润减少,水肿和肾损伤评分降低,TNF-α、IL-6、IL-1β及NF-κB p65的表达以及p-NF-κB蛋白水平显著下降,Nrf2与HO-1蛋白表达显著增加(P均<0.05)。结论盐酸小檗胺能够有效保护脓毒症引起的小鼠急性肾损伤,其保护作用可能与抑制NF-κB信号通路的活化,下调相关炎症因子的表达,以及激活Nrf2/HO-1信号通路,减轻氧化应激反应有关。Objective To investigate the protective effect and mechanism of Berbamine Hydrochloride(BBM)on sepsis with acute kidney injury in mice.Methods 24 C57BL/6J mice were randomly divided into 4 groups with 6 mice in each group:control group(CON),model group(LPS),model+Berbamine hydrochloride group(LPS+BBM)and Berbamine hydrochloride group(BBM).The model of septic-shock-associated acute kidney injury(SA-AKI)was prepared by intraperitoneal injection with LPS.The pathological changes of renal tissue in each group were observed by HE staining.The expression of inflammatory factors TNF-α,IL-6,IL-1βand NF-κB p65 in renal tissues were detected by immunofluorescence assay.MDA and SOD kits were used to detect SOD activity and MDA content.The expression of nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and p-NF-κB proteins in renal tissues were detected by Western blot assay.Results Compared with LPS group,BBM treatment could decrease inflammatory infiltration,alleviated edema,decreased renal injury score,the levels of inflammatory factors TNF-α,IL-6,IL-1β,NF-κB p65,and the content of MDA,increase SOD activity.In addition,BBM also significantly increased the expression of Nrf2 and HO-1.Conclusion Berbamine hydrochloride may reduce SA-AKI by relieving p-NF-κB activity and expression of inflammatory factors,activating Nrf2/HO-1 signaling pathway.

关 键 词：盐酸小檗胺 脓毒症急性肾损伤 炎症 氧化应激 NF-ΚB Nrf2/HO-1 

分 类 号：R332[医药卫生—人体生理学]