多肽类化合物Urantide对动脉粥样硬化大鼠心脏组织中骨桥蛋白和α平滑肌肌动蛋白表达的影响

Effect of urantide on the expression of osteopontin and α-smooth muscle actin in the heart of atherosclerotic rats

目的观察Urantide对动脉粥样硬化(AS)大鼠心脏组织中骨桥蛋白(OPN)和α平滑肌肌动蛋白(α-SMA)表达的影响,探讨其防治大鼠心肌纤维化损伤的作用机制。方法选取120只3周龄SPF级健康雄性Wistar大鼠,高脂饲料饲养及腹腔注射维生素D3(Vit D3)的方法建立AS大鼠模型,按照随机化原则分为:对照组、AS模型组、辛伐他汀组、Urantide(3 d、7 d、14 d)组。采用HE和Masson三色染色法观察大鼠心脏组织形态和胶原纤维表达情况,免疫组织化学和Western blotting检测大鼠心脏组织OPN和α-SMA蛋白表达情况。结果 AS模型组大鼠心脏组织中出现心肌细胞肥大或萎缩、大量炎性细胞浸润和少量泡沫细胞等病理变化;心脏组织胶原纤维增多及OPN和α-SMA蛋白表达水平较对照组显著升高。与AS模型组相比,经Urantide治疗后心脏组织损伤明显改善,胶原纤维和OPN及α-SMA蛋白表达水平降低。结论 Urantide可以抑制AS大鼠心脏组织中OPN和α-SMA蛋白表达,缓解心肌纤维化,同时保护AS大鼠的心肌组织。

Objective To observe the effect of urantide on the expression of osteopontin(OPN) and α-smooth muscle actin(α-SMA) in the heart tissue of atherosclerosis(AS) rats,and to explore its mechanism of prevention and treatment of myocardial fibrosis injury in rats.Methods Totally 120 3-week-old healthy male Wistar rats in SPF grade were randomly divided into six groups: control group,model group,simvastatin group,urantide(3 days,7 days,14 days).HE and Masson trichrome staining were used to observe the morphology of rat heart and the expression of collagen fibers.Immunohistochemistry and Western blotting were used to detect the expression of OPN and α-SMA protein.Results In AS model group,cardiomyocyte hypertrophy or atrophy,a large number of inflammatory cell infiltration and a small amount of foam cells were observed in the heart tissue of rats.The increase of collagen fibers and the expression of OPN andα-SMA protein in cardiac tissue were significantly higher than those in the control group.Compared with the AS model group,after urantide treatment,cardiac injury was significantly improved,and the expression of collagen fiber,OPN andα-SMA protein was decreased.Conclusion Urantide can inhibit the expression of OPN and α-SMA protein in the heart tissue of AS rats to alleviate myocardial fibrosis and play a protective role in the heart tissue of AS rats.