虎杖苷对脓毒症急性肾损伤小鼠线粒体心磷脂合成的影响及机制  

The effect and mechanism of polydatin on the cardiolipin synthesis of the septic acute kidney injury

作　　者：雷小保[1] 丁琼蕾 李涛[1] 邓加雄 LEI Xiao⁃bao;DING Qiong⁃lei;LI Tao;DENG Jia⁃xiong(Department of Critical Care Medicine,the First People's 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》2022年第7期906-909,1033,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(ZDYF2020013,ZDYF2019024);湘南学院自然科学项目(2019XJ86)

摘　　要：目的探讨虎杖苷对脓毒症急性肾损伤(SAKI)中心磷脂合成及线粒体损伤的影响及可能机制。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。对照组小鼠接受开腹术后予以溶剂处理;药物对照组小鼠接受开腹术后予以虎杖苷(30 mg/kg)处理;模型组小鼠接受CLP术后予以溶剂处理;治疗组小鼠接受CLP术后予以虎杖苷(30 mg/kg)处理;抑制剂组小鼠接受CLP术后予以虎杖苷(30 mg/kg)及沉默信息调节因子2相关酶3(SIRT3)抑制剂3-TYP(5 mg/kg)处理。采用Western blot法检测心磷脂合成酶1(CLS1)表达,分别使用三磷酸腺苷(ATP)、心磷脂(CL)和活性氧(ROS)试剂盒检测肾脏ATP、细胞CL及ROS水平,JC-1探针检测线粒体膜电位(MMP),自动生化分析仪检测血清肌酐及尿素氮水平。结果与对照组比较,模型组CLS1、CL、ATP及MMP水平分别显著下降为(70.0±6.5)%、(16.5±5.6)μg/mg蛋白、(0.70±0.08)μmol/g组织及(55.0±3.5)%(P均<0.05),ROS、肌酐及尿素氮水平分别显著增加为(254.0±25.1)%、(60.0±11.7)μmol/L及(24.8±7.1)mmol/L(P均<0.05)。与模型组比较,治疗组CLS1、CL、ATP及MMP水平分别显著增加为(89.0±6.0)%、(23.5±5.2)μg/mg蛋白、(0.93±0.13)μmol/g组织及(77.0±7.4)%(P均<0.05),ROS、肌酐及尿素氮水平分别显著下降为(163.0±12.8)%、(40.0±7.0)μmol/L及(17.5±3.8)mmol/L(P均<0.05)。与治疗组比较,抑制剂组CLS1、CL、ATP及MMP水平分别显著下降为(69.0±7.0)%、(16.3±3.9)μg/mg蛋白、(0.75±0.08)μmol/g组织及(64.0±5.4)%(P均<0.05),ROS、肌酐及尿素氮水平分别显著增加为(226.0±19.5)%、(59.0±10.2)μmol/L及(28.0±5.5)mmol/L(P均<0.05)。结论虎杖苷通过SIRT3改善CLS1表达,促进CL合成,减轻SKAI中线粒体损伤。Objective To investigate the effects and mechanism of polydatin on the cardiolipin(CL)synthesis and mitochondrial injury of the septic acute kidney injury(SAKI).Methods Mice 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 regulation2homolog-3(SIRT3).The expression of cardiolipin synthetase 1(CLS1)was detected by Western blot.The content of CL,adenosine triphosphate(ATP)and reactive oxygen species(ROS)were determined by commercial kits.The mitochondrial membrane potential(MMP)was detected by JC-1.The concentrations of creatinine and urea nitrogen in serum were measured by an automatic biochemical analyzer.Results Compared with the control group,the expression of CLS1,CL content,ATP level and MMP in model group were respectively decreased to(70.0±6.5)%,(16.5±5.6)μg/mg protein,(0.70±0.08)μmol/g tissue and(55.0±3.5)%(all P<0.05);the ROS level,serum creatinine and nitrogen in model group were respectively increased to(54.0±25.1)%,(60.0±11.7)μmol/L and(24.8±7.1)mmol/L(all P<0.05).Compared with the model group,the expression of CLS1,CL content,ATP level and MMP in treatment group were respectively increased to(89.0±6.0)%,(23.5±5.2)μg/mg protein,(0.93±0.13)μmol/g tissue and(77.0±7.4)%(all P<0.05);the ROS level,serum creatinine and nitrogen in treatment group were respectively decreased to(163.0±12.8)%,(40.0±7.0)μmol/L and(17.5±3.8)mmol/L(all P<0.05).Compared with the treatment group,the expression of CLS1,CL content,ATP level and MMP in inhibitor group were respectively d

关 键 词：虎杖苷 脓毒症 急性肾损伤 心磷脂 线粒体 

分 类 号：R285.5[医药卫生—中药学]