【摘要】 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、ATF4 mRNA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、ATF4 mRNA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、ATF4 mRNA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。更多还原

【Abstract】 Objective To determine the effect of crocin regulating miR-139-5p/ATF4 axis on myocardial injury and energy metabolism in rats with CHF.Methods A total of 84 male 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.Cardiac 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-139-5p 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 cTnI,cTnT,CK-MB,NT-proBNP,TNF-α and IL-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).Compared with the crocin high-dose group, the crocin+miR-139-5p inhibitor group had higher apoptotic rate of cardiomyocytes [(22.68±3.25)% vs(11.94±1.38)%,P<0.05],increased LVEDD and LVESD value, raised MAD content and cTnI,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-139-5p level(P<0.05).There was a targeting relationship between miR-139-5p and ATF4.Conclusion Crocin can improve myocardial injury and energy metabolism in CHF rats, which may be related to its regulation of miR-139-5p/ATF4 axis.更多还原