卵磷脂型二十碳五烯酸对细菌脂多糖所致急性肾损伤的影响  

The effect of eicosapentaenoic acid-enriched phosphatidylcholine on lipopolysaccharide induced acute kidney injury in mice

作　　者：韩潇 郑燕[2] 杨玉红 郭欣 吴昊 杜磊 HAN Xiao;ZHENG Yan;YANG Yuhong;GUO Xin;WU Hao;DU Lei(Department of Nutrition and Food Hygiene,School of Public Health,Cheeloo College of Medicine,Shandong University,Ji'nan 250012,China;Research Center of Translational Medicine,Ji'nan Central Hospital,Ji'nan 250013,China;School of Food Science and Engineering,Qilu University of Technology(Shandong Academy of Sciences),Ji'nan 250353,China)

机构地区：[1]山东大学齐鲁医学院公共卫生学院营养与食品卫生学系,山东济南250012 [2]济南市中心医院专科转化研究中心,山东济南250013 [3]齐鲁工业大学(山东省科学院)食品科学与工程学部,山东济南250353

出　　处：《中国海洋药物》2023年第6期13-20,共8页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金青年科学基金项目(82003447);山东大学青年学者未来计划项目(2018WLJH34)资助。

摘　　要：目的探讨卵磷脂型二十碳五烯酸(EPA-PC)对细菌脂多糖(LPS)所致小鼠急性肾脏损伤的影响。方法24只雄性C57BL/6J小鼠随机分为正常对照组、LPS染毒组和EPA-PC干预组,以400 mg/(kg·bw)剂量灌胃EPA-PC4周后,经腹腔注射LPS 10 mg/(kg·bw)染毒。称量并记录小鼠体质量和肾脏质量,计算肾系数;检测小鼠血清中血尿素氮(BUN)和肌酐(CRE)水平;观察肾脏组织病理变化、炎性细胞浸润情况以及活性氧水平;测定肾脏中肾损伤分子1(KIM-1)、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、白介素6(IL-6)和NADPH氧化酶4(NOX4)mRNA表达水平;测定肾脏丙二醛(MDA)水平;过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活性;谷胱甘肽(GSH)含量和总抗氧化能力(T-AOC);检测肾脏NOX4蛋白表达水平。结果与LPS染毒组相比,EPA-PC干预显著降低小鼠肾质量和肾系数;降低血清BUN和CRE含量,下调肾脏KIM-1、TNF-α、IL-1β和IL-6 mRNA表达水平,改善肾脏病理损伤、肾脏巨噬细胞和中性粒细胞浸润;降低肾脏活性氧水平和MDA含量,提高肾脏CAT活性、SOD活性、GSH水平以及总抗氧化能力;下调肾脏NOX4 mRNA和蛋白表达水平。结论EPA-PC可通过下调NOX4表达改善炎症和氧化应激进而保护LPS所致小鼠急性肾损伤。Objective To investigate the effect of eicosapentaenoic acid-enriched phosphatidylcholine(EPA-PC)on lipopolysaccharide(LPS)-induced acute kidney injury in mice.Methods Twenty-four C57BL/6J male mice were randomly divided into 3 groups,i.e.Control group,LPS group and EPA-PC+LPS group.The EPA-PC+LPS group was given EPA-PC by intragastric administration at a dose of 400 mg/(kg·bw)for 4-week intervention.Then,the mice were injected intraperitoneally with 10 mg/(kg·bw)LPS.The body weight and kidney weight of mice were weighed and recorded.The renal index was calculated.The blood urea nitrogen(BUN)and creatinine(CRE)levels in the serum were measured.The histopathology,inflammatory cell infiltration and reactive oxygen species(ROS)levels were observed.The mRNA levels of kidney injury molecule 1(KIM-1),tumor necrosis factor alpha(TNF-α),interleukin 1beta(IL-1β),interleukin 6(IL-6)and NADPH oxidase 4(NOX4)were measured.The renal malondialdehyde(MDA)activity,catalase(CAT)activity,superoxide dismutase(SOD)activity,glutathione(GSH)content and total antioxidant capacity(T-AOC)were tested.The protein expression of NOX4 in the kidney of mice was determined.Results Compared with LPS-treated mice,pretreatment with EPA-PC significantly inhibited LPS-induced the increase of kidney weight,renal index,blood urea nitrogen(BUN)and creatinine(CRE)levels in mice.EPA-PC pretreatment down-regulated the renal mRNA levels of KIM-1,TNF-α,IL-1βand IL-6 mRNA expression in the kidney of LPS-treated mice.Pretreatment with EPA-PL protected renal pathological injury and relieved the infiltration of macrophages and neutrophils.EPA-PC pretreatment ameliorated renal oxidative stress in LPStreated mice,indicated by decreasing ROS and MDA levels as well as increasing CAT and SOD activates,GSH content and T-AOC.EPA-PC pretreatment down-regulated renal NOX4 mRNA and protein levels in LPS-treated mice.Conclusion EPA-PC protected LPS-induced acute kidney injury in mice through attenuating inflammation and oxidative stress via down-regulating NOX4.

关 键 词：卵磷脂型二十碳五烯酸 急性肾损伤 脂多糖 炎症 氧化应激 

分 类 号：R151.3[医药卫生—营养与食品卫生学]