DUSP9在2型糖尿病心肌病小鼠心肌损伤中的保护作用及其机制
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中图分类号：R542.2，R587.2 文献标志码：A DOI：10.11958/20253111
Abstract：ObjectiveTo investigatethe protective efectand underlying mechanism dual-specificityphosphatase9 （DUSP9）on myocardial injury in mice with type2 diabeticcardiomyopathy （DCM）.MethodsA mouse model type 2 diabetes was established usinga high-fat，high-sugardietcombined with intraperitonealinjection streptozotocin （STZ）. After successful modeling，the mice wererandomlydivided intothecontrol group（control），thediabetes melitus （DM）group， the diabetes + empty vector （DM+Vector） group and the diabetes + DUSP9 overexpression （DM + DUSP9） group. Following a 12-week intervention viatail vein injection AAV9-DUSP9 or emptyviral vector，cardiac function wasassessed by echocardiography.Thebody weight，fasting blood glucoseand heart massratio weredetected inmiceeach group.Heart tissue sampleswerecollctedforhistological examinationusing HEandWGAstaining toobservemyocardial pathological changes. The levels inflammatory cytokines IL-6 and TNF- α in myocardial tissue were measured by ELISA.Myocardial cell apoptosiswasdetectedbyTUNELassay.Thephosphorylation levelsERKandp38proteins wereevaluated by Western blot assy.Mitochondrial morphological changes were observedvia transmission electron microscopy.Results Compared with the control group，significantly increased heart weight，heart-to-body weight ratio，cardiomyocytecross sectional area，levels IL-6and TNF- α in myocardial tissue， myocardial cell apoptosis rate and expressions p-ERK and p-p38 in myocardial tissue were observed in the DM group and the DM + Vector group，and left ventricular ejection fraction （LVEF）and left ventricular fractional shortening （LVFS） were significantly decreased （ P<0.05 ）.Comparedwith theDM + Vectorgroup，the DM + DUSP9group exhibited significantly decreased heart weight，heart-to-body weight ratio， cardiomyocyte cross-sectional area，levels IL-6 and TNF- α ，myocardial cell apoptosis rate and expressions Δp -ERK and p-p38，while LVEF and LVFS were significantly increased （ P<0.05 ）. ConclusionDUSP9 overexpression improves cardiacfunction in diabetic mice.The mechanismmay berelated totheinhibition ERKandp38phosphorylation by DUSP9，therebyaleviating myocardialinflammation，apoptosis andmitochondrial damage indiabeticcardiomyopathymice.
Key words： diabeticcardiomyopathies; mitogen-activated protein kinase kinases; apoptosis;mitochondria;dual-specificity phosphatases; inflammation
糖尿病心肌病（diabeticcardiomyopathy，DCM）是2型糖尿病（T2DM常见的心血管并发症，以心肌结构和功能异常为主要特征[1]。（剩余11977字）