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目的:观察诊断级低强度超声联合微泡对糖尿病心肌病(diabetic cardiomyopathy,DCM)大鼠心肌微循环的改善作用,并初步探讨其可能机制。方法:健康雄性SD大鼠通过腹腔注射链脲佐菌素(65 mg/kg)后高脂高糖饮食建立2型DCM大鼠模型。实验随机分为3组:正常对照组(15只)、糖尿病心肌病模型组(DCM组,15只)、超声联合SonoVue微泡组(US+MB组,15只)。采用诊断超声VFLASH技术进行干预治疗,干预2周后常规超声心动图评估心功能。处死后取出心肌组织,行CD31免疫组化测定心肌微血管密度(MVD),Western Blot检测大鼠心肌组织PI3K-Akt-eNOS通路蛋白的表达。结果:与DCM组相比,US+MB组大鼠左室射血分数(LVEF)和左心室短轴缩短率(LVFS)明显增大[(68.97±4.84)%对(57.76±6.03)%,(34.01±3.97)%对(27.70±3.24)%,均n P<0.05],MVD数量明显增多(27.66±3.39对10.67±1.63,n P<0.05)。Western Blot结果显示,与DCM组比较,US+MB组大鼠心肌组织磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)、蛋白激酶B(protein kinase B,PKB/Akt)蛋白表达量及PI3K蛋白的磷酸化水平明显增加[(0.44±0.04)%对(0.28±0.05)%,(0.36±0.04)%对(0.21±0.05)%,(0.42±0.06)%对(0.26±0.05)%,均n P0.05]。n 结论:诊断级低强度超声联合微泡可以在一定程度上改善心肌微循环,促进心肌功能恢复,其机制可能与增加PI3K-Akt-eNOS通路有关。“,”Objective:To observe the effect and mechanism of diagnostic low intensity ultrasound combined with microbubbles on myocardial microcirculation in rats with diabetic cardiomyopathy (DCM).Methods:The healthy male SD rats were induced DCM by streptozotocin through intraperitoneal injection and fed with high fat diet. The rats were randomly divided into normal control group (n n=15), DCM model group (DCM group, n n=15), and the SonoVue microbubble + US group (US+ MB group, n n=15). After 2 weeks of intervention using diagnostic ultrasound combined with VFLASH, all rats underwent conventional echocardiograph to examine the cardiac function. The rats were sacrificed and myocardial tissue was stained with CD31 immunohistochemistry to quantify myocardial microvascular density (MVD). The expressions of PI3K-Akt-eNOS pathway protein in rats myocardium were detected by Western blot.n Results:The left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) in the US+ MB grouph were significantly increased compared with DCM group [(68.97±4.84) % vs (57.76±6.03)%, (34.01±3.97)% vs (27.70±3.24)%, all n P<0.05]. The MVD in US+ MB group was significantly higher than that in the DCM group(27.66±3.39 vs 10.67±1.63,n P<0.05). The protein level of phosphatidylinositol 3-kinase(PI3K), protein kinase B(PKB/Akt) and PI3K phosphorylation in myocardial tissue of rats increased significantly in US+ MB group compared with DCM group [(0.44±0.04)% vs (0.28±0.05)%, (0.36±0.04)% vs (0.21±0.05)%, (0.42±0.06)% vs (0.26±0.05)%, alln P0.05].n Conclusions:Diagnostic low intensity ultrasound combined with microbubbles can enhance myocardial microcirculation and improve myocardial function to some extent, and the mechanism may be related to the activation of PI3K-Akt-eNOS pathways.