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目的研究超声靶向破坏微泡(ultrasound targeted microbubble destruction,UTMD)技术转染H-FABP基因对心肌梗死后心功能的影响。方法通过结扎成年雄性Wistar大鼠46只,体质量(220±20)g,冠状动脉前降支建立心肌梗死模型。于心肌梗死8周后,将存活的31只心衰大鼠随机分为4组:①H-FABP+超声+微泡组(H-FABP+US/MB组,n=8),用超声破坏携H-FABP基因微泡转染大鼠心肌;②超声+微泡组(US/MB组,n=8),用超声破坏不含基因的微泡;③H-FABP+生理盐水组(H-FABP+NS组,n=8),由颈静脉输入含基因的生理盐水;④单纯手术组(SA组,n=7),仅由颈静脉输入生理盐水;⑤假手术组(SS组,n=6)。基因转染14 d后测定各组大鼠心功能,Western blot检测左心室非梗死区H-FABP表达,ELISA法检测静脉血及非梗死区心肌游离脂肪酸(FFA)含量,硫代巴比妥酸反应物(TBARS)法检测非梗死区心肌组织脂质过氧化水平,免疫组织化学法检测非梗死区心肌诱导型一氧化氮合酶(iNOS)表达。结果心肌梗死大鼠各组与假手术组比较心功能明显下降(P<0.05),H-FABP表达明显下降(P<0.05),静脉血及心肌FFA含量明显升高(P<0.05),丙二醛(MDA)水平明显升高(P<0.05),iNOS表达明显升高(P<0.05)。H-FABP+超声+微泡组与心肌梗死大鼠中的另外3组比较心功能明显改善(P<0.05),H-FABP表达升高(P<0.05),心肌FFA含量降低(P<0.05),MDA水平降低(P<0.05),iNOS表达受抑制(P<0.05)。结论超声微泡介导的H-FABP转染可改善大鼠慢性心衰时心功能。可能与通过提高H-FABP表达、降低心肌FFA含量、改善心肌氧化应激水平、进而抑制iNOS的表达有关。
Objective To investigate the effect of ultrasound-targeted microbubble destruction (UTMD) technology on H-FABP gene transfection after cardiac infarction. Methods 46 adult male Wistar rats were ligated and their myocardial mass was (220 ± 20) g. The model of myocardial infarction was established by anterior descending coronary artery. After 8 weeks of myocardial infarction, 31 surviving rats were randomly divided into 4 groups: ① H-FABP + ultrasound + microbubble group (H-FABP + US / MB group, n = 8) FABP gene micro-vesicles were transfected into the myocardium of rats; ②Ultrasound + microbubbles group (US / MB group, n = 8) (N = 6, n = 8, n = 8). The saline was injected into the jugular vein from the jugular vein. ④ In the simple operation group (SA group, n = 7), saline was injected only into the jugular vein. . The cardiac function of rats in each group was determined 14 days after transfection, the expression of H-FABP in non-infarcted area of left ventricle was detected by Western blot, the level of free fatty acid (FFA) in venous blood and non-infarcted area was detected by ELISA, The levels of lipid peroxidation in myocardium of non-infarcted area were detected by TBARS method and the expression of iNOS in non-infarcted area was detected by immunohistochemical method. Results Compared with the sham-operation group, the cardiac function of myocardial infarction rats was significantly decreased (P <0.05), the expression of H-FABP was significantly decreased (P <0.05), the content of FFA in venous blood and myocardium was significantly increased The level of MDA was significantly increased (P <0.05) and the expression of iNOS was significantly increased (P <0.05). Compared with the other three groups, H-FABP + ultrasound microbubbles group had significantly improved cardiac function (P <0.05), H-FABP expression increased (P < , MDA level decreased (P <0.05), iNOS expression was inhibited (P <0.05). Conclusion Ultrasound microbubble-mediated H-FABP transfection can improve heart function in rats with chronic heart failure. It may be related to increasing the expression of H-FABP, decreasing the myocardial FFA content, improving the myocardial oxidative stress level, and then inhibiting the expression of iNOS.