缬沙坦对甲亢性心脏病大鼠心肌组织TGF-β1、Smad3和Smad7表达的影响

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目的:探讨缬沙坦对甲亢性心脏病大鼠左室心肌组织中TGF-β1、Smad3和Smad7表达的影响。方法:SD大鼠40只,随机分为对照组、模型组、缬沙坦小剂量组(VL组)和缬沙坦大剂量组(VH组)。模型组、VL和VH组予L-甲状腺素0.5mg/(kg.d)腹腔注射28d,VL组和VH组在建模同时灌胃缬沙坦10和30mg/(kg.d)。造模前后分别采取静脉血,用化学发光法检测血清TT3、TT4水平;第28天行超声心动图检测左室舒张末期内径(LVDD)、左室后壁(LVPW)厚度、室间隔(IVS)厚度;计算心肌肥厚指标;HE染色和Masson染色观察左室心肌组织形态结构,测定左心室肌细胞直径和胶原容积分数,免疫组化法观察TGF-β1、Smad3及Smad7的表达。结果:与对照组相比,模型组大鼠左室腔扩大,室壁增厚,左心指数、心肌细胞直径、胶原容积分数增大;左心室心肌组织TGF-β1、Smad3表达明显增强,Smad7表达略有增加。VH和VL组心肌重构指标均较模型组改善,心肌组织TGF-β1、Smad3表达下降,而Smad7表达明显上升;VH和VL组间各指标差异无统计学意义(P>0.05)。结论:缬沙坦可通过调节TGF-β1、Smad3及Smad7的表达,抑制心肌重构,保护心功能。 Objective: To investigate the effects of valsartan on the expression of TGF-β1, Smad3 and Smad7 in left ventricular myocardium of hyperthyroid heart disease rats. Methods: Forty SD rats were randomly divided into control group, model group, low dose valsartan group (VL group) and high dose valsartan group (VH group). The model group, VL and VH groups were given intraperitoneal injection of L-thyroxine 0.5 mg / (kg · d) for 28 days. VL group and VH group were given valsartan 10 and 30 mg / (kg · d) at the same time. Venous blood samples were taken before and after modeling, and serum TT3 and TT4 levels were detected by chemiluminescence. On the 28th day, left ventricular end-diastolic diameter (LVDD), left ventricular posterior wall thickness (LVPW), interventricular septum (IVS) Thickness, the indexes of cardiac hypertrophy were calculated. The morphology of left ventricular myocardium was observed by HE staining and Masson staining. The diameter and collagen volume fraction of left ventricular myocytes were measured. The expressions of TGF-β1, Smad3 and Smad7 were observed by immunohistochemistry. Results: Compared with the control group, the left ventricular cavity enlargement, ventricular wall thickening, left ventricular index, myocardial cell diameter and collagen volume fraction increased in model group. The expressions of TGF-β1 and Smad3 in left ventricular myocardium were significantly increased The expression increased slightly. The indexes of myocardial remodeling in VH and VL groups were improved compared with those in model group. The expressions of TGF-β1 and Smad3 in myocardium were decreased, while the expression of Smad7 in VH and VL group was significantly increased. There was no significant difference between VH and VL group (P> 0.05). Conclusion: Valsartan can inhibit cardiac remodeling and protect heart function through regulating the expression of TGF-β1, Smad3 and Smad7.
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