缬沙坦对自发性高血压大鼠心肌细胞外基质重塑和氧化应激态的影响

Effect of valsartan on myocardial extracelluar matrix remodeling and oxidative stress in vessels of rats with spontaneous hypertensin

目的研究缬沙坦对高血压诱发的心肌细胞外基质重塑和氧化应激态的影响。方法选用16w龄雄性自发性高血压大鼠(SHR)12只,随机分为2组,缬沙坦组和阴性对照组(SHR组),每组6只。另选同周龄雄性Wistar-Kyoto大鼠(WKY)6只作为正常对照组(WKY组),给药6w后测定血清Ⅲ型前胶原(PIIIP)、Ⅳ型前胶原(PIVP)、透明质酸透射(HA)、心肌羟脯氨酸和胶原蛋白含量,电镜观察心肌超微结构,同时检测血清和心肌组织活性氧(ROS)水平、超氧化酶歧化酶(SOD)活力、丙二醛(MDA)含量。结果给药6w后,缬沙坦组血清PIIIP、PIVP、HA含量、心肌羟脯氨酸和胶原蛋白含量明显低于SHR组(P<0.01);电镜显示缬沙坦组心肌与SHR组比较,肌原纤维较清晰,排列整齐,横纹清楚,间质胶原纤维无明显增生;缬沙坦组血清和心肌组织SOD活力明显高于SHR组,而ROS水平、MDA含量明显低于SHR组(P<0.01)。结论缬沙坦可改善高血压诱发的心肌细胞外基质重塑,其机制与其抗氧化应激作用有关。

Objective To explore the effect of valsartan on myocardial extracelluar matrix remodeling and oxidative stress induced by hypertension.MethodSixteen weeks old male spontaneously hypertensive rats(SHR) were randomly divided into two groups each of which has six rats:valsartan group and negative control group (SHR group). Six same weeks old mate Wistar-Kyoto rats (WKY) were selected as normal control group (WKY group).After all rats were fed with drugs for six weeks. The serum levels of pro-collagen Ⅲ(PⅢP),pro-collagen Ⅳ(PⅣP),hyaluronic acid(HA),the levels of myocardical hydroxyproline and collagen protein were separately determined.Ultrastructure of cardiac muscle was observed with transmission electron microscope.Simultaneously the levels of serumal and myocardical SOD、MDA were determined.ResultsAfter 6 weeks,the serum levels of PⅢP,PⅣP,HA and the levels of myocardical hydroxyproline and collagen protein of valsartan group were significantly lower than those of SHR group (P<0.01). Electron microscope displayed that compared with SHR group,myofibrils were clearer,their rank was orderly,transverse striations in them were clear and interstitial collagen fibers didn't hyperplasy obviously in cardiac muscle of valsartan group;The levels of Serumal and myocardical SOD of vatsartan group were significantly higher,while the levels of serumal and myocardical MDA were significantly lower than those of SHR group (P<0.01).ConclusionsValsartan can improve myocardial extracelluar matrix remodeling induced by hypertension,the mechanism of which may be related with antioxidation.