抗纤益心方对扩张型心肌病大鼠心肌能量代谢和解偶联蛋白2的影响

Effects of Kangxian Yixin Decoction on Energy Metabolism and Uncoupling Protein 2 in Rats with Dilated Cardiomyopathy

目的:探讨抗纤益心方对扩张型心肌病(DCM)大鼠心肌能量代谢变化和解偶联蛋白2的影响及其作用机制。方法:将80只SD大鼠随机选取8只作为正常对照组,其余大鼠采用呋喃唑酮水溶液诱导DCM模型,将造模成功的大鼠随机分为模型对照组、抗纤益心方1.8、3.6 g/kg组、辅酶Q10 20.0 mg/kg组,药物治疗8 w。超声心动仪检测大鼠心脏左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、缩短分数(FS)、左室射血分数(LVEF)的变化;HE染色观察大鼠心肌组织病理学改变;透射电镜观察线粒体超微结构;酶联免疫吸附(ELISA)法测定血清丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、三磷酸腺苷酶(ATPase)含量;蛋白免疫印迹(Western blot)检测解偶联蛋白2(UCP2)的表达。结果:与正常对照组相比,模型对照组大鼠LVESD、 LVEDD和心脏指数明显升高,FS和EF明显降低,心肌组织病理损伤明显,线粒体排列紊乱,肿胀伴空泡样变化,MDA含量明显增加,SOD活力、ATPase含量明显降低(P<0.05),UCP2蛋白表达明显上调(P<0.05);与模型对照组比较,抗纤益心方3.6 g/kg组和辅酶Q10 20.0 mg/kg组LVESD、LVEDD和心脏指数降低,FS和EF明显增加,心肌组织损伤明显减轻,线粒体形态结构的损伤改善,MDA含量降低,SOD活力和ATPase含量明显升高,UCP2蛋白表达明显下调(P<0.05)。结论:抗纤益心方改善DCM大鼠心肌能量代谢和心脏功能,其作用机制可能与下调UCP2蛋白表达有关。

Objective:To investigate the effects and mechanism of Kangxian Yixin Decoction(KYD) on energy metabolism and uncoupling protein 2(UCP2) in rats with dilated cardiomyopathy(DCM). Methods:From the selected 80 SD rats, eight were classified into the normal control group. The remaining ones were treated with furazolidone aqueous solution to induce DCM. The successfully modeled rats were randomized into the model group, coenzyme Q10(20.0 mg/kg) group, and low-(1.8 g/kg) and high-dose(3.6 g/kg) KYD groups, and then administrated with the corresponding drugs for eight weeks. The changes in left ventricular end-systolic diameter(LVESD), left ventricular end-diastolic diameter(LVEDD), shortening fraction(FS) and left ventricular ejection fraction(LVEF) were detected by echocardiography. The rat myocardium was stained with HE for observing the histopathological changes. The mitochondrial ultrastructure was observed under a transmission electron microscope. The malondialdehyde(MDA) content, superoxide dismutase(SOD) activity and adenosine triphosphatase(ATPase) levels were determined by enzyme-linked immunosorbent assay(ELISA). Western blotting was carried out to detect UCP2 expression. Results:Compared with the normal control group, the model group exhibited significantly increased LVESD, LVEDD, cardiac index and MDA, decreased FS, EF, SOD and ATPase, obvious pathological damages in myocardial tissue, manifested as mitochondrial swelling and vacuolation arranged in disorder(P<0.05), and up-regulated UCP2 protein expression(P<0.05). Compared with the model group, KYD at 3.6 g/kg and coenzyme Q10 at 20.0 mg/kg both lowered LVESD, LVEDD, cardiac index and MDA, elevated FS,EF, SOD and ATPase, alleviated the myocardial tissue damage, improved the mitochondrial structure, and down-regulated UCP2 protein expression(P<0.05). Conclusion:KYD improves energy metabolism and cardiac function of rats with DCM possibly by down-regulating the UCP2 protein expression.