法舒地尔对压力超负荷大鼠左心室肥厚的改善作用
Protective effect of fasudil against left ventricular hypertrophy in rats with pressure overload
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摘要: 目的:探讨法舒地尔对压力超负荷大鼠左心室肥厚的影响及可能的作用机制。方法:42只6周龄SD大鼠行腹主动脉缩窄术制备压力超负荷模型作为手术组,另取8只大鼠作为假手术组(Sham组)。术后4周将存活的28只腹主动脉缩窄大鼠随机分为模型组(Model组)、法舒地尔高剂量组(FH组)和法舒地尔低剂量组(FL组)。4周后,计算各组大鼠左心室质量指数(LVMI),观察心肌病理改变,检测心肌细胞直径(MD),碱水法测定心肌羟脯氨酸(HYP)含量,酶联免疫吸附试验测定血浆和心肌血管紧张素Ⅱ(AngⅡ)浓度,免疫组织化学法半定量分析心肌磷酸化肌球蛋白磷酸酶靶蛋白亚基1(p-MYPT1)、基质金属蛋白酶9(MMP9)和组织金属蛋白酶组织抑制剂1(TIMP1)的表达水平。结果:与Sham组比较,Model组心肌细胞肥大,间质大量胶原沉积,LVMI、MD、HYP含量和AngⅡ浓度均明显升高,p-MYPT1、MMP9和TIMP1的表达显著上调,MMP9/TIMP1比值明显下降(P<0.01);与Model组比较,FH组和FL组心肌细胞肥大和胶原沉积有所改善,LVMI、MD、HYP和AngⅡ含量均下降(P<0.05~P<0.01),p-MYPT1、MMP9和TIMP1的表达均明显下调(P<0.01)。结论:法舒地尔改善压力超负荷大鼠左心室肥厚的作用可能与调节心肌MMP9和TIMP1表达有关。Abstract: Objective: To investigate the effects of fasudil on left ventricular hypertrophy in rats with pressure overload, and its possible mechanism. Methods: Pressure overload model in 42 male 6-week-old SD rats were established by abdominal aorta constriction, and divided into the operation group. Eight healthy rats were set as sham group. Twenty-eight survival abdominal aorta constriction rats after 4 weeks of operation were randomly divided into the model group, high dose fasudil group(FH group) and low dose fasudil group(FL group). After four weeks of drug intervention, the left ventricular mass indexes(LVMI) of all groups were calculated. The myocardial pathological changes were observed. The myocyte diameters(MD) were detected. Myocardial hydroxyproline(HYP) contents were determinated by alkali hydrolysis. Plasma and myocardial AngⅡ concentrations were detected by enzyme linked immunosorbent assay. Myocardial expression levels of phosphorylated myosin phosphatase targeting protein subunit 1(p-MYPT1), matrix metalloproteinase 9(MMP9) and tissue inhibitor of metalloproteinase 1(TIMP1) were analyzed by immunohistochemical staining. Results: Compared with the sham group, myocardial cells hypertrophy and collagen deposition in myocardial interstitium were found, the levels of LVMI, MD, HYP, AngⅡ, p-MYPT1, MMP9 and TIMP1 increased significantly, and the ratio of MMP9/TIMP1 decreased significantly in model group(P<0.01). Compared with the model group, myocardial cells hypertrophy and collagen deposition were improved, and the levels of LVMI, MD, HYP, Ang Ⅱ, p-MYPT1, MMP9, TIMP1 decreased significantly in FH group and FL group(P<0.05 to P<0.01). Conclusions: Fasudil improving left ventricular hypertrophy in pressure overload rats maybe related to the regulating myocardial MMP9 and TIMP1 expression levels
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Key words:
- left ventricular hypertrophy /
- fasudil /
- pressure overload /
- rat
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