藏红花素对慢性心力衰竭大鼠心肌损伤和能量代谢的影响

Effect of crocin on myocardial injury and energy metabolism in rats with chronic heart failure

目的探讨藏红花素调控微小RNA-139-5p(miR-139-5p)/激活转录因子4(ATF4)轴对慢性心力衰竭(CHF)大鼠心肌损伤及能量代谢的影响。方法选择SPF级雄性SD大鼠84只,随机分为假手术组、模型组、藏红花素低、中、高剂量组、卡托普利组、藏红花素+miR-139-5p抑制剂组,每组12只。检测大鼠心功能指标、心肌组织病理学形态、细胞凋亡率、心肌损伤指标、心力衰竭指标、炎性指标、氧化应激指标、心肌组织ATP含量、琥珀酸脱氢酶(SDH)活性、miR-139-5p、ATF4mRNA表达水平,验证miR-139-5p与ATF4的靶向关系。结果与模型组比较,藏红花素各剂量组心肌细胞凋亡率、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、肌钙蛋白I(cTnI)、肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、N末端B型钠尿肽前体(NT-proBNP)、TNF-α、白细胞介素1β(IL-1β)、丙二醛、ATF4mRNA表达降低,LVEF、左心室短轴缩短率(LVFS)、超氧化物歧化酶(SOD)、ATP含量、SDH活性、miR-139-5p表达升高(P<0.05)。藏红花素+miR-139-5p抑制剂组心肌细胞凋亡率高于藏红花素高剂量组[(22.68±3.25)%vs(11.94±1.38)%,P<0.05]。与藏红花素高剂量组比较,藏红花素+miR-139-5p抑制剂组LVEDD、LVESD、cTnI、cTnT、CK-MB、NT-proBNP、TNF-α、IL-1β、丙二醛、ATF4mRNA表达升高,LVEF、LVFS、SOD、ATP含量、SDH活性、miR-139-5p表达降低(P<0.05)。miR-139-5p与ATF4存在靶向关系。结论藏红花素可改善CHF大鼠心肌损伤及能量代谢,其机制可能与调控miR-139-5p/ATF4轴有关。

Objective To determine the eefect of crocin regulating miR-139-5P/ATF4 axis on myo-cardial injury and energy metabolism in rats with CHF.Methods A total of 84 maee SPF SD rats were randomly divided into sham oPeration group,model group,crocin low-,medium-and high-dose groups,captopril group and crocin±miR-139-5P inhibitor grouP,with 12 in each grouP.Car-diac function indexes,myocardial histomathological morPhology,aPOPtotic rate,myocardial injury indexes,heart failure indexes,inflammatory indexes,oxidative stress indexes,myocardial ATP content,SDH activity,and miR-139-5P and ATF4 mRNA exPression levels were detected in rats.The targeting relationshiP between miR-139±P and ATF4 was verified.Results Compared with the conditions in the model grouP,crocin treatment at different doses reduced aPOPtotic rate of cardiomyocytes,decreased MDA content,LVEDD and LVESD values and cTnl,cTnT,CK-MB,NT-ProBNP,TNF-α and 1L-1β levels,and declined ATF4 mRNA level,and increased LVEF and LVFS values,SOD activity,ATP content,SDH activity and miR-139-5P level(P<0.05).Corn-Pared with the crocin high-dose grouP,the crocin±miR-139±P inhibitor grouP had higher aPOP-totic rate of cardiomyocytes[(22.68±3.25)%vs(11.94±1.38)%,P<0.05],increased LVEDD and LVESD value,raised MAD content and cTnl,cTnT,CK-MB,NT-proBNP,TNF-α and IL-1β level,and elecated ATF4 mRNA level,and decreased LVEF and LVFS value,SOD activity,ATP content,SDH activity and miR-139-5β level(P<0.05).There was a targeting relationship between mi R-139-5p and ATF4.Conclusion Crocin can improve myocardial injury and energy me-tabolism in CHF rats,which may be related to its regulation of miR-139-5p/ATF4 axis.