Rhodioloside inhibits the activation of NLRP3 inflammasome and alleviates doxorubicin-induced cardiotoxicity by regulating FGF2 expression
Objective It is to explore the protective effect of Rhodioloside(Rhod)on doxorubicin(DOX)-induced cardiotoxicity(DIC)and its molecular mechanism.Methods ①Eighteen 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 experi-ment,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 my-ocardial 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-l β precursor(Pro-IL-1β),IL-1 β,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 0.5 μmol/L doxorubicin for 48 h),DOX+Rhod group(treated with 0.5 μmol/L doxorubicin+10 μg/mL Rhod for 48 h)and DOX+Rhod+FGF2 antibody group(treated with 0.5 μmol/L doxorubicin+10 μg/mL Rhod+0.1 μg/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.Results ①On 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 signifi-cantly lower than that in the control group(P＜0.05),while there was no significant difference between the model group and Rhod group(P＞0.05).On the 14th day of modeling,the LVEF,HW/TL and LV/TL of mice in the model group were lower than those in the control group(all P＜0.05),and these indexes in the Rhod group were all significantly higher than those in the model group(all P＜0.05).On the 14th day of experiment,the relative contents of MDA in myocardial tissue homogenate(total)and mitochondrial of myocardial tissue,the content of ROS in myocardial tissue,and the relative protein expressions of IL-1 β,NLRP3,Caspase-1 p20 in myocardial tissues of mice in the model group were significantly higher than those in the control group(all P＞0.05),while these indexes in the Rhod group were all significantly lower than those in the model group(all P＜0.05);the relative protein expressions of Pro-Caspase-1 in myocardial tissues of mice in the model group were significantly lower than those in the control group(all P＞0.05),while the Rhod group were significantly higher than the model group(P＜0.05);there was no significant difference in the relative content of MDA in cytoplasmic of myocardial tissue,relative expression of Pro-IL-1 β in myocardial tissues among each group(all P＞0.05).②The cell viability OD value and the relative expression of FGF2 protein in the cells of the DOX group were significantly lower than those of the blank group(both P＜0.05);the cell viability OD value of the DOX+Rhod group was higher than those of DOX group and DOX+Rhod+FGF2 antibody group(both P＜0.05);the relative expressions of FGF2 protein in the cells of the DOX+Rhod group and DOX+Rhod+FGF2 antibody group were higher than that of the DOX group(both P＜0.05),but there was no significant difference between the DOX+Rhod group and DOX+Rhod+FGF2 antibody group(P＞0.05).Conclusion Rhod can alleviate doxorubicin-induced cardiotoxicity by up-regulating the expression of FGF2 and inhibiting the activation of NLRP3 inflammasome.
万方数据
维普
