基于FGF2表达探讨红景天苷对阿霉素诱导的心脏毒性的保护作用及对NLRP3炎症小体的影响  

Rhodioloside inhibits the activation of NLRP3 inflammasome and alleviates doxorubicin-induced cardiotoxicity by regulating FGF2 expression

作　　者：陈鹏[1] 刘石琳 朱小蕾 王晓慧[1] 冷静[1] CHEN Peng;LIU Shilin;ZHU Xiaolei;WANG Xiaohui;LENG Jing(The Second Affiliated Hospital of Xinjiang Medical University,Urumq 830000,Xinjiang,China)

机构地区：[1]新疆医科大学第二附属医院,新疆乌鲁木齐830000

出　　处：《现代中西医结合杂志》2024年第13期1794-1800,1806,共8页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：新疆维吾尔自治区自然科学基金资助项目(2022D01C318)。

摘　　要：目的探讨红景天苷对阿霉素诱导的心脏毒性的保护作用及分子机制。方法①将18只雄性C57BL/6J小鼠随机分为对照组、模型组、红景天苷组,每组6只。对照组不做处理;模型组和红景天苷组分别于实验第1天、第2天、第4天尾静脉注射阿霉素6 mg/kg,红景天苷组在实验第1天时于阿霉素注射前腹腔注射红景天苷8 mg/kg。分别于实验第1天、第7天和第14天称量小鼠体重,超声心动图测定左心室射血分数(LVEF)。实验第14天,处死小鼠后称心脏和左心室质量,测量胫骨长度,计算心脏质量/胫骨长度比值和左心室质量/胫骨长度比值,硫代巴比妥酸法测定心肌组织匀浆(总)、心肌组织线粒体部分、心肌组织细胞质部分中丙二醛(MDA)相对含量,DHE荧光探针法测定心肌组织匀浆(总)中活性氧(ROS)含量,Western blot法检测心肌组织中白细胞介素-1β前体(Pro-IL-1β)、IL-1β、NLRP3、半胱氨酸天冬氨酸蛋白水解酶1(Caspase-1)前体(Pro-Caspase-1)、Caspase-1 p20蛋白表达情况。②取大鼠H9c2心肌细胞,实验设空白组(细胞不做处理)、阿霉素组(加入0.5μmol/L阿霉素处理48 h)、阿霉素+红景天苷组(加入0.5μmol/L阿霉素和10μg/mL红景天苷处理48 h)、阿霉素+红景天苷+FGF2抗体组(加入0.5μmol/L阿霉素+10μg/mL红景天苷+0.1μg/mL FGF2抗体处理48 h),CCK-8测定细胞活力,Western blot法测定细胞中FGF2蛋白表达情况。结果①实验第1天、第7天和第14天,3组小鼠体重比较差异均无统计学意义(P均>0.05)。实验第7天,模型组和红景天苷组小鼠LVEF均明显低于对照组(P均<0.05),模型组和红景天苷组比较差异无统计学意义(P>0.05);造模第14天,模型组小鼠LVEF、心脏质量/胫骨长度比值和左心室质量/胫骨长度比值均明显低于对照组(P均<0.05),红景天苷组均明显高于模型组(P均<0.05)。实验第14天,模型组小鼠心肌组织(总)MDA相对含量、心肌细胞线粒体部分MDA相对含量Objective It is to explore the protective effect of Rhodioloside(Rhod)on doxorubicin(DOX)-induced cardiotoxicity(DIC)and its molecular mechanism.Methods①Eighteen male C57BL/6J mice were randomly divided into control group,model group and Rhod group,with 6 mice in each group.The control group was not treated;the model group and Rhod group were injected with 6 mg/kg doxorubicin through tail vein on the 1st,2nd and 4th day of the experiment,respectively,the Rhod group was intraperitoneally injected with 8 mg/kg Rhod before doxorubicin administration on the 1st day.On the 1st,2nd and 4th day of the experiment,the mice were executed,and their heart weight(HW)and left ventricular weight(LVW)were weighed and their tibia length(TL)was measured,and the HW/TL and LVW/TL were calculated,the relative contents of malondialdehyde(MDA)in myocardial tissue homogenate(total),mitochondrial of myocardial tissue,and cytoplasmic of myocardial tissue were determined by thiobarbituric acid assay,the content of reactive oxygen species(ROS)in myocardial tissue homogenate(total)was determined by DHE fluorescent probe assay,and the protein expressions of interleukin-1βprecursor(Pro-IL-1β),IL-1β,NLRP3,Caspase-1 precursor(Pro-Caspase-1),and Caspase-1 p20 in myocardial tissues were detected by Western blot assay.②The rat H9c2 myocardial cells were taken and divided into blank group(the cells were not treated),DOX group(treated with 0.5μmol/L doxorubicin for 48 h),DOX+Rhod group(treated with 0.5μmol/L doxorubicin+10μg/mL Rhod for 48 h)and DOX+Rhod+FGF2 antibody group(treated with 0.5μmol/L doxorubicin+10μg/mL Rhod+0.1μg/mL FGF2 antibody for 48 h).The cell viability of each group was detected by CCK-8,and the relative expression of FGF2 in the cells was determined by Western blot.Results①On the 1st,2nd and 4th day of the experiment,there was no significant difference in body weight among the three groups(all P>0.05).On the 7th day of the experiment,the LVEF of mice in both the model group and Rhod group were significantly lower t

关 键 词：阿霉素 心脏毒性 红景天苷 NLRP3炎症小体 成纤维细胞生长因子2 

分 类 号：R-332[医药卫生]