贵州医科大学学报

2021, v.46;No.254(11) 1301-1308

[打印本页] [关闭]
本期目录(Current Issue) | 过刊浏览(Past Issue) | 高级检索(Advanced Search)

猫爪草对缺血再灌注小鼠急性肾损伤的作用及机制
The alleviating effect and possible mechanism of ranunculus ternatus thunb on acute kidney injury induced by ischemia reperfusion in mice

余婷;张妮;陈思羽;王笑笑;左思洋;郭兵;刘丽荣;
YU Ting;ZHANG Ni;CHEN Siyu;WANG Xiaoxioa;ZUO Siyang;GUO Bing;LIU Lirong;Center for Clinical Laboratories,the Affiliated Hospital of Guizhou Medical University;School of Clinical Laboratory Science,Guizhou Medical University;Guizhou Provincial Key Laboratory of Common Chronic Disease Pathogenesis and Drug Research,Guizhou Medical University;

摘要(Abstract):

目的探讨猫爪草(RTT)对缺血再灌注(IR)小鼠急性肾损伤(AKI)的作用及其可能机制。方法 15只雄性C57BL/6小鼠随机均分为假手术组(sham组)、IR组、RTT预处理组(IR+RTT组),IR+RTT组术前14 d每天按2 g/kg剂量予RTT预灌胃处理,IR组和sham组给予等体积双蒸水灌胃;sham组小鼠仅钝性剥离肾蒂,另两组小鼠夹闭双侧肾蒂45 min构建IR模型;术后24 h处死小鼠,取眼球血液及肾脏;生化法检测血肌酐(Scr)和尿素氮(BUN),HE染色观察肾组织改变,免疫组织化学、Western blot检测中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肿瘤坏死因子-α(TNF-α)、组蛋白H3赖氨酸36三甲基化(H3K36me3)、组蛋白H3赖氨酸4三甲基化(H3K4me3)的表达变化,Pearson相关性分析H3K36me3、H3K4me3、TNF-α与NGAL的相关性。结果 IR组小鼠血清Scr和BUN高于sham组(P<0.05),IR+RTT组小鼠血清Scr和BUN低于IR组(P<0.05);HE染色显示,sham组小鼠肾小管和肾小球形态结构清晰,IR组肾小管上皮细胞出现肿胀、脱落、坏死,IR+RTT组肾脏病变明显改善;免疫组织化学、Western blot结果显示,与sham组相比,IR组小鼠肾脏组织NGAL、TNF-α、H3K36me3、H3K4me3蛋白水平上调(P<0.05);与IR组相比,IR+RTT组小鼠肾脏组织NGAL、 TNF-α、H3K36me3、H3K4me3蛋白水平下调(P<0.05);Pearson相关性分析结果显示,IR-AKI小鼠肾组织H3K36me3、H3K4me3、TNF-α与NGAL表达水平均呈正相关关系(r=0.739、0.782、0.713,P<0.05)。结论 RTT对IR-AKI小鼠肾功能及肾组织损伤具有预防作用,其机制可能与下调H3K36me3、H3K4me3、TNF-α表达进而抑制炎症反应有关。
Objective To investigate the alleviating effect and possible mechanism of Ranunculus ternatus thunb(RTT) on acute kidney injury(AKI) induced by ischemia reperfusion(IR) in mice,and to provide new ideas and directions for clinical prevention and treatment of AKI.Methods Fifteen male C57 BL/6 mice were randomly divided into the sham operation group,IR group and IR+RTT group,with 5 mice in each group.IR+RTT group was preperfused with 2 g/kg RTT per day for14 days before operation,while IR group and sham group were given the same volume of double distilled water,and eyeball blood and kidneys were collected.The IR mouse model was established by clamping bilateral renal pedicle for 45 min,while the sham group was only performed with blunt stripping pedicle,and all mice were killed 24 hours after operation,then eyeball blood and kidneys were collected.Serum creatinine(Scr) and urea nitrogen(BUN),the indicators of renal function were detected by biochemical method.HE staining was used to observe the pathological changes of renal tissues.Immunohistochemical and Western blot were used to measure the expression of neutrophil gelatinase-associated lipocalin(NGAL),tumor necrosis factor-α(TNF-α),Tri-methylation of Histone H3 lysine 36(H3 K36 me3),and Tri-methylation of Histone H3 lysine 4(H3 K4 me3).Pearson Correlation Coefficient was used to analyze the correlations between H3 K36 me3,H3 K4 me3,TNF-α,and NGAL.Results Biochemical results showed that compared with the sham group,Scr and BUN levelswere significantly higher in IR group(P <0.05),and compared with IR group,the levels were significantly lower in IR+RTT group(P <0.05).HE staining showed significant morphological structure of renal tubules and glomeruli in sham group,and swelling,shedding,and necrosis in renal tubular epithelial cells in IR group,and there was obvious improvement of lesions in IR+RTT group.Immunohistochemical and Western blot showed that the protein levels of NGAL,TNF-α,H3 K36 me3,and H3 K4 me3 were significantly up-regulated in IR group compared with the sham group(P <0.05),and the protein levels of NGAL,TNF-α,H3 K36 me3,and H3 K4 me3 were significantly downregulated in IR+RTT group compared with IR group(P <0.05).Pearson correlation analysis showed that the expression of H3 K36 me3,H3 K4 me3,TNF-α were significantly positively correlated with the expression of NGAL(r=0.739、0.782、0.713,P <0.05).Conclusion RTT has a preventive effect on the injury of renal function and tissues in IR-AKI mice.It may be closely related to the inhibition of inflammatory response that is caused by down-regulating the expression of H3 K36 me3,H3 K4 me3,TNF-α.

关键词(KeyWords): 缺血再灌注损伤;急性肾损伤;猫爪草;小鼠;组蛋白H3赖氨酸36三甲基化;组蛋白H3赖氨酸4三甲基化
ischemia reperfusion(IR);acute kidney injury(AKI);ranunculus ternatus thunb(RTT);mice;tri-methylation of histone H3 lysine 36(H3K36me3);tri-methylation of histone H3 lysine 4(H3K4me3)

Abstract:

Keywords:

基金项目(Foundation): 贵州省高层次留学人才创新创业择优资助项目[留学人才择优资助合同(2018)01];; 大学生创新创业训练计划立项项目(20195200148)

作者(Authors): 余婷;张妮;陈思羽;王笑笑;左思洋;郭兵;刘丽荣;
YU Ting;ZHANG Ni;CHEN Siyu;WANG Xiaoxioa;ZUO Siyang;GUO Bing;LIU Lirong;Center for Clinical Laboratories,the Affiliated Hospital of Guizhou Medical University;School of Clinical Laboratory Science,Guizhou Medical University;Guizhou Provincial Key Laboratory of Common Chronic Disease Pathogenesis and Drug Research,Guizhou Medical University;

DOI: 10.19367/j.cnki.2096-8388.2021.11.010

参考文献(References):

文章评论(Comment):

序号(No.) 时间(Time) 反馈人(User) 邮箱(Email) 标题(Title) 内容(Content)
反馈人(User) 邮箱地址(Email)
反馈标题(Title)
反馈内容(Content)
扩展功能
本文信息
服务与反馈
本文关键词相关文章
本文作者相关文章
中国知网
分享