虎杖苷通过SIRT3减轻脓毒症急性肾损伤小鼠炎症反应、氧化应激及细胞凋亡  

Polydatin could mitigate the inflammation,oxidative stress and apoptosis via SIRT3 in the septic acute kidney injury of the mice

作　　者：雷小保[1] 李涛[1] LEI Xiao-bao;LI Tao(Department of Critical Care Medicine,the First Peopled Hospital of Chenzhou,Chenzhou,Hunan 423000,China)

机构地区：[1]郴州市第一人民医院重症医学科,湖南郴州423000

出　　处：《热带医学杂志》2021年第7期831-834,F0002,共5页Journal of Tropical Medicine

基　　金：国家自然科学基金(81500066);郴州市科技发展计划项目(zdyf201924);郴州市第一人民医院院内项目(N2019-057)。

摘　　要：目的探讨虎杖苷对脓毒症急性肾损伤(SAKI)中炎症反应、氧化应激及细胞凋亡的影响及可能机制。方法通过盲肠结扎穿孔(CLP)法建立SAKI模型。30只小鼠随机分为5组,每组6只。对照组:建立假模型后接受溶剂处理;药物对照组:建立假模型后接受虎杖苷(30 mg/kg)处理;模型组:建立SAKI模型后接受溶剂处理;治疗组:建立SAKI模型后接受虎杖苷(30 mg/kg)处理;抑制剂组:建立SAKI模型后接受虎杖苷(30 mg/kg)及SIRT3抑制剂3-TYP(5 mg/kg)处理。检测肾组织丙二醛(MDA)含量、还原型谷胱甘肽(GSH)/氧化型谷胱甘肽(GSSG)比值、超氧化物歧化酶(SOD)活力、总抗氧化能力(T-AOC)。采用TUNEL染色法检测肾组织细胞凋亡,酶联免疫法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平。结果与对照组比较,模型组GSH/GSSG、SOD及T-AOC分别显著下降为(4.4±0.5)U/(mg·pr)、(8.4±2.2)U/(mg·pr)及(0.6±0.1)μmol/(mg·pr),MDA、凋亡细胞数、TNF-α、IL-1β及IL-6分别显著增加为(6.2±0.7)nmol/(mg·pr)、(38.5±9.2)、(362.2±36.5)pg/mL、(295.2±37.4)pg/mL及(858.2±56.8)ng/mL。与模型组比较,治疗组GSH/GSSG、SOD及T-AOC分别显著增加为(12.5±2.3)U/(mg·pr)、(29.5±3.3)U/(mg·pr)及(1.0±0.2)μmol/(mg·pr),MDA、凋亡细胞数、TNF-α、IL-1β及IL-6分别显著下降为(3.0±0.3)nmol/(mg·pr)、(15.3±3.9)、(287.5±15.9)pg/mL、(187.8±20.5)pg/mL及(463.0±50.9)ng/mL。与治疗组比较,抑制剂组GSH/GSSG、SOD及T-AOC分别显著下降为(6.2±0.8)U/(mg·pr)、(20.1±2.8)U/(mg·pr)及(0.7±0.2)μmol/(mg·pr),MDA、凋亡细胞数、TNF-α、IL-1β及IL-6分别显著增加为(5.7±0.7)nmol/(mg·pr)、(36.8±6.0)、(345.7±27.6)pg/mL、(250.5±37.3)pg/mL及(818.7±58.1)ng/mL。结论虎杖苷通过SIRT3改善SKAI小鼠氧化应激、细胞凋亡及炎症反应。Objective To investigate the effects and mechanism of polydatin on the inflammation,oxidative stress and apoptosis in the septic acute kidney injury(SAKI)of the mice.Methods Mice were underwent cecal ligation and puncture(CLP)to mimic SAKI.A total of 30 mice were randomly divided into five groups:mice in control group received a sham SAKI model and treatment with vehicle;mice in drug-control group received a sham SAKI model and treatment with polydatin(30 mg/kg);mice in model group received a SAKI model and treatment with vehicle;mice in treatment group received a SAKI model and treatment with polydatin(30 mg/kg);mice in inhibitor group received a SAKI model and treatment with polydatin(30 mg/kg)and 3-TYP(5 mg/kg).The inhibitor of silent mating type information regulation 2 homolog-3(SIRT3),the malondialdehyde(MDA)content,glutathione(GSH)/glutathione oxidized(GSSG),superoxide dismutase(SOD)activity,and total antioxidant capacity(T-AOC)were detected by kits.The cell apoptosis was determined by the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-Triphosphate-Digoxigenin nick end labeling(TUNEL)assay.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were determined by ELISA kits.Results Compared with the control group,the GSH/GSSG,SOD and T-AOC in model group were respectively decreased to(4.4±0.5)U/(mg·pr),(8.4±2.2)U/(mg·pr)and(0.6±0.1)μmol/(mg·pr);the MDA and apoptotic cell in kidney,the serum concentration of TNF-α,IL-1βand IL-6 in model group were respectively increased to(6.2±0.7)nmol/(mg·pr),(38.5±9.2),(362.2±36.5)pg/mL,(295.2±37.4)pg/mL and(858.2±56.8)ng/mL.Compared with the model group,the GSH/GSSG,SOD and T-AOC in treatment group were respectively increased to(12.5±2.3)U/(mg·pr),(29.5±3.3)U/(mg·pr)and(1.0±0.2)μmol/(mg·pr);the MDA and apoptotic cell in kidney,the serum concentration of TNF-α,IL-1β and IL-6 in treatment group were respectively decreased to(3.0±0.3)nmol/(mg·pr),(15.3±3.9),(287.5±15.9)pg/mL,(1

关 键 词：虎杖苷 急性肾损伤 氧化应激 凋亡 

分 类 号：R459.7[医药卫生—急诊医学] K692[医药卫生—治疗学]