水苏糖抑制铁死亡和炎症对小鼠心肌缺血再灌注损伤的影响OA

Objective It is to investigate the protective effect and possible mechanism of stachyose on myocardial ische-mia-reperfusion injury(MIRI)in mice.Methods The male C57BL/6J mice were divided into sham operation group,a my-ocardial ischemia-reperfusion group and stachyose group by a random number table,with 6 mice in each group.At 3 days before surgery,the mice in the stachyose group were given stachyose 5 g/(kg·day)via gavage,while the mice in the oth-er groups were given an equal volume of normal saline via gavage.On the 4th day of the experiment,the MIRI models were established in the myocardial ischemia-reperfusion group and stachyose group.After 45 minutes of myocardial ischemia and 24 hours of reperfusion,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were detected by cardiac echocardiography,the area of myocardial infarction was measured,the myocardial tissue pathology was observed by HE staining,the serum levels of creatine kinase(CK-MB),lactate dehydrogenase(LDH),cardiac tropo-nin I(cTnI),and interleukin-1β(IL-1β)were measured by ELISA,the protein expression of IL-1β in myocardial tissue was detected by Western blot analysis,the expressions of lipid peroxides and Fe2+in myocardial tissue were detected by Li-pofluo and FerroOrange staining,the expressions of ferroptosis-related genes[glutathione peroxidase(GPX4)and prosta-glandin-endoperoxide synthase 2(PTGS2)]and inflammatory factors[IL-1β,tumor necrosis factor-α(TNF-α)and inter-leukin-6(IL-6)]in myocardial tissue were detected by quantitative real-time PCR.Results Compared with the sham oper-ation group,the LVEF and LVFS of mice in the myocardial ischemia-reperfusion group were significantly reduced(all P<0.05);the area of myocardial infarction was significantly increased,with myocardial fiber rupture accompanied by massive inflammatory cell infiltration;the serum levels of CK-MB,LDH,cTnI and IL-1β were all significantly increased(all P<0.05);the relative protein expression of IL-1β,the fluorescence intensities of lipid peroxides and Fe2+,and the relative mRNA expressions of TNF-α,IL-1β,IL-6 and PTGS2 in myocardial tissue were all significantly increased(all P<0.05),while the relative mRNA expression of GPX4 in myocardial tissue was significantly reduced(P<0.05).Compared with the myocardial ischemia-reperfusion group,the LVEF and LVFS of mice in the stachyose group were significantly increased(all P<0.05);the area of myocardial infarction was significantly decreased,and the myocardial injury was attenuated;the ser-um levels of CK-MB,LDH,cTnI and IL-1β were all significantly decreased(all P<0.05);the relative protein expression of IL-1β,the fluorescence intensities of lipid peroxides and Fe2+,and the relative mRNA expressions of TNF-α,IL-1β,IL-6 and PTGS2 in myocardial tissue were all significantly decreased(all P<0.05),while the relative mRNA expression of GPX4 in myocardial tissue was significantly increased(P<0.05).Conclusion Stachyose can attenuate MIRI,and its cardioprotective effect may be achieved by inhibiting ferroptosis and inflammatory response.