酮体对小鼠脓毒症急性肾损伤的保护作用及其机制的研究  

Investigation on the Protective Effect of Ketone Body on LPS-induced Acute Kidney Injury in Mice and Its Mechanism

作　　者：张家丽 佐拉木·买买提[1] 于虎 ZHANG Jiali;ZUOLAMU Maimaiti;YU Hu(Department of Nephrology,People′s Hospital of Xinjiang Uygur Autonomous Region,Xinjiang 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院肾病科ICU,乌鲁木齐830001 [2]新疆维吾尔自治区人民医院急救中心,乌鲁木齐830001

出　　处：《医学研究杂志》2022年第10期34-38,共5页Journal of Medical Research

基　　金：新疆维吾尔自治区自然科学基金资助项目(2018D01C146)。

摘　　要：目的探讨酮体对脓毒症小鼠急性肾损伤(acute kidney injury,AKI)的保护作用及可能机制。方法采用随机分组对照研究的方法,将18只C57BL/6J雄性小鼠随机分为对照组、模型组和实验组,每组6只。实验组连续3天灌胃酮脂,对照组和模型组灌胃0.9%氯化钠溶液,第3天灌胃结束后30min对模型组和实验组小鼠腹腔注射LPS诱导脓毒症AKI,对照组腹腔注射等量0.9%氯化钠溶液。24h后处死小鼠,取尿液、血浆和两侧肾脏。测定各组小鼠血酮水平;检测各组小鼠肾功能相关指标包括肌酐(serum creatinine,SCr)、尿素氮(blood urea nitrogen,BUN)、尿微量白蛋白/尿肌酐(urine albumin/creatinine,UALb/Cr)和肾损伤分子1(kidney injury molecule 1,KIM-1)的值;苏木精-伊红染色观察各组小鼠肾组织病理改变;检测氧化应激相关指标包括丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)和过氧化氢酶(catalase,CAT)活性;Western blot法检测各组小鼠肾组织中FoxO3a和SOD2蛋白水平。结果与对照组比较,模型组小鼠SCr、BUN、UALb/Cr和KIM-1水平均大幅升高,同时伴有明显的肾小管上皮细胞肿胀或脱落、间质水肿和肾小管扩张;组织MDA含量明显增加,SOD、GSH和CAT活性降低;FoxO3a和SOD2表达明显下降。与模型组小鼠比较,实验组小鼠血酮浓度上升,肾功能得到改善,肾组织病理损伤明显减轻,肾脏氧化应激损伤减轻,FoxO3a和SOD2表达有所升高。结论酮体可以通过抑制氧化应激对LPS诱导的脓毒症小鼠肾损伤起到保护作用,其机制可能是促进FoxO3a和SOD2抗氧化蛋白的表达。Objective To investigate the protective effect of ketone body on LPS-induced AKI in mice and its possible mechanism.Methods By using a randomized controlled study,eighteen male C57BL/6J mice were randomly divided into three groups:control group,model group and experimental group,with 6 mice in each group.The experimental group mice were given ketone ester for three consecutive days by gavage,and the control group and the model group were intragastric with saline and then both the experimental group and model group mice were given LPS by intraperitoneal injection at 30 minute after the ketone ester was given on day 3 to induce AKI.The control group was intraperitoneally injected with the same amount of saline.The mice were sacrificed 24 hours later,and urine,plasma and kidneys were collected.Serum ketone levels were determined.Levels of BUN,SCr,KIM-1,and UAlb/Cr were calculated to assess the renal function.Hematoxylin-eosin staining was used to observe the pathological changes of renal tissues in each group.MDA content,SOD,GSH and CAT activities were analyzed to estimate the degree of oxidative stress.FoxO3a and SOD2 protein expressions of mice renal tissue in each group were detected by western blotting.Results Compared with the control group,the levels of SCr,BUN,UALb/Cr and KIM-1 in the model group were significantly increased,accompanied by obvious tubule epithelial cell swelling or exfoliation,interstitial edema and tubule dilatation.MDA content increased significantly.SOD,GSH and CAT activities decreased.FoxO3a and SOD2 protein expression decreased significantly.Compared with model group,serum ketone concentration was increased.Renal function was improved,pathological injury of renal tissue was significantly alleviated,oxidative stress injury of kidney was alleviated,and FoxO3a and SOD2 protein expression were increased in the experimental group.Conclusion ketone body can protect against the LPS-induced AKI in mice by inhibiting oxidative stress and the mechanism may be to promote the expression of FoxO3a an

关 键 词：酮体 急性肾损伤 氧化应激 FOXO3A SOD2 

分 类 号：R587.1[医药卫生—内分泌]