胡黄连苷Ⅱ调节cGAS-STING信号通路对感染性休克大鼠心肌损伤的保护作用  

Protective effect of picrosideⅡon myocardial injury in septic shock rats by regulatingc GAS-STING signaling pathway

作　　者：王梦梦 杨开宁 闫瑾 丁乾[3] 胡菊[2] WANG Meng-meng;YANG Kai-ning;YAN Jin;DING Qian;HU Ju(Department of Pharmacy,the Second Central Hospital of Baoding City,Hebei Province,Baoding 072750,China;Department of Laboratory,the Second Central Hospital of Baoding City,Hebei Province,Baoding 072750,China;Department of Traditional Chinese Medicine,the Second Central Hospital of Baoding City,Hebei Province,Baoding 072750,China)

机构地区：[1]河北省保定市第二中心医院药剂科,河北保定072750 [2]河北省保定市第二中心医院检验科,河北保定072750 [3]河北省保定市第二中心医院中医科,河北保定072750

出　　处：《河北医科大学学报》2025年第4期436-443,共8页Journal of Hebei Medical University

基　　金：保定市科技计划项目(2241ZF017)。

摘　　要：目的分析胡黄连苷Ⅱ(picrosideⅡ,Pic-Ⅱ)调节环鸟苷酸-腺苷酸合成酶(cyclic guanylate adenylate synthetase,cGAS)-干扰素基因刺激蛋白(stimulator of interferon genes,STING)信号通路对感染性休克大鼠心肌损伤的保护作用。方法将大鼠随机分为6组:假手术组、模型组、Pic-Ⅱ低治疗组、Pic-Ⅱ中治疗组、Pic-Ⅱ高治疗组和激活剂组,每组10只。除假手术组外,其余组采用盲肠结扎穿孔术构建感染性休克大鼠模型。超声心动图检测各组大鼠心功能,HE染色观察心肌组织病理变化,TUNEL染色观察心肌细胞凋亡情况,采用试剂盒法检测心肌损伤标志物肌钙蛋白Ⅰ(cardiac troponinⅠ,cTnⅠ)、脑利钠肽(brain natriuretic peptide,BNP)和肌酸激脢(creatine kinase-MB,CK-MB),酶联免疫吸附实验检测心肌组织白细胞介素(interleukin,IL)-1β、IL-8和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)水平,Western blot检测心肌组织cGAS-STING通路蛋白。结果与假手术组比较,模型组心肌纤维紊乱,心肌细胞变性坏死、左心室缩短分数(left ventricular fraction shorting,LVFS)、左心室射血分数(left ventricular ejection fraction,LVEF)降低,左心室舒张末期内径(left ventricular end diastolic diameter,LVEDD)、心肌细胞凋亡率增加,cTnⅠ、BNP、CK-MB、IL-1β、IL-8、TNF-α、cGAS、STING、p-TANK结合激酶1(TANK-binding kinase 1,TBK1)/TBK1、磷酸化干扰素调节因子3(phosphorylated-interferon regulatory factor 3,p-IRF3)/干扰素调节因子3(interferon regulatory factor 3,IRF3)表达升高(P<0.05);与模型组比较,Pic-Ⅱ低治疗组、Pic-Ⅱ中治疗组、Pic-Ⅱ高治疗组心肌损伤程度减轻,心肌细胞排列规律恢复,LVFS、LVEF升高,LVEDD、心肌细胞凋亡率下降,cTnⅠ、BNP、CK-MB、IL-1β、IL-8、TNF-α、cGAS、STING、p-TBK1/TBK1、p-IRF3/IRF3表达降低(P<0.05);与Pic-Ⅱ高治疗组比较,激活剂组心肌损伤进一步加重,LVFS、LVEF降低,LVEDD、心肌细胞凋亡率增加,cTnⅠ、BNObjective To analyze the protective effect of picrosideⅡ(Pic-Ⅱ)on myocardial injury in septic shock rats by regulating the cyclic guanylate adenylate synthetase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods Rats were randomly separated into six groups:Sham group,model group,low,medium,and high Pic-Ⅱtreatment groups,and activator group,with 10 rats in each group.Except the Sham group,the other groups received cecal ligation and perforation surgery to construct a rat model of septic shock.Ultrasound echocardiography was applied to detect the cardiac function of rats in each group.HE staining was applied to observe pathological changes in myocardial tissue,and TUNEL staining was applied to observe myocardial cell apoptosis.The kit method was applied to detect myocardial injury markers,including cardiac troponinⅠ(cTnⅠ),brain natriuretic peptide(BNP),and creatine kinase-MB(CK-MB).Enzyme-linked immunosorbent assay(ELISA)was applied to measure interleukin(IL)-1β,IL-8,and tumor necrosis factor-α(TNF-α)in myocardial tissue,and Western blot was applied to measure cGAS-STING pathway proteins in myocardial tissue.Results Compared with Sham group,the model group showed myocardial fiber disorder,myocardial cell degeneration and necrosis,decreased the left ventricular fraction shorting(LVFS)and left ventricular ejection fraction(LVEF),increased left ventricular end diastolic diameter(LVEDD)and myocardial cell apoptosis rate,and increased level of cTnⅠ,BNP,CK-MB,IL-1β,IL-8,TNF-α,cGAS,STING,p-TANK-binding kinase 1(TBK1)/TBK1,and phosphorylated-interferon regulatory factor 3(p-IRF3)/interferon regulatory factor 3(IRF3)(P<0.05).Compared with the model group,the degree of myocardial injury in low,medium,and high Pic-Ⅱtreatment groups was reduced,and the arrangement of myocardial cells was restored to a regular pattern;the LVFS and LVEF were increased,the LVEDD and myocardial cell apoptosis rate were reduced,and the cTnⅠ,BNP,CK-MB,IL-1β,IL-8,TNF-α,cGAS,STING,p-TBK1/TBK1,and p-IRF3/IRF3 we

关 键 词：休克 心肌损伤 胡黄连苷Ⅱ 

分 类 号：R631.4[医药卫生—外科学]