【摘要】 目的以钙调神经磷酸酶(Ca N)和钙蛋白酶Ⅰ(CalpainⅠ)为研究对象,探讨美托洛尔预防腹主动脉缩窄大鼠心肌肥厚的机制。方法 30只SD大鼠建立腹主动脉缩窄模型,造模成功者随机分为假手术组(n=10)、腹主动脉缩窄手术组(n=9)和美托洛尔组(n=9,在腹主动脉缩窄基础上每日予美托洛尔干预)。术后4周检测大鼠血压[收缩压(SBP)/舒张压(DBP)]及心肌肥厚程度变化[左心室质量/体质量的比值(LVW/BW表示)],逆转录PCR(RT-PCR)法检测Ca N m RNA表达,Western blot法检测Ca N和CalpainⅠ蛋白表达。检测各组的Ca N酶活性。结果手术组大鼠SBP、DBP、LVW/BW,心肌Ca N m RNA、Ca N蛋白、Ca N活性及CalpainⅠ蛋白表达均较假手术组增高(P<0.05)。美托洛尔组大鼠SBP、DBP虽较手术组略下降,但差异无统计学意义(P>0.05),且仍高于假手术组(P<0.05)。与手术组相比,美托洛尔组大鼠LVW/BW、心肌中Ca N m RNA、蛋白表达和酶活性,CalpainⅠ蛋白显著下降(P<0.05),与假手术组差异均无统计学意义。结论美托洛尔可通过抑制CalpainⅠ,调控Ca N信号通路,从而预防压力超负荷大鼠心肌肥厚的发生。更多还原

【Abstract】 Objective To study the mechanism of metoprolol preventing pressure overload induced myocardialhypertrophy through inhibiting calcineurin(Ca N) and Calpain Ⅰ signaling pathway in rat model of coarctation of abdominalaorta.MethodsThirty SD rats were used for hypertension rat model induced by coarctation of suprarenal abdominal aorta.Model rats were divided into three groups, sham operation group(n=10), abdominal aortic coarctation group(n=9) andmetoprolol group(n=9). The changes of blood pressure [systolic blood pressure(SBP) and diastolic blood pressure(DBP)] andmyocardial hypertrophy [the ratio of left ventricular mass/body mass(LVW/BW)] were measured. RT-PCR was used todetect the expression of Ca N m RNA, and Western blot assay was used to detect expressions of Ca N and Calpain Ⅰ proteins.The activity of Ca N enzyme was detected and compared between three groups.ResultsCompared with the sham-operatedsham operation group, values of SBP, DBP, LVW/BW, protein expressions and activities of Ca N m RNA, Ca N and Calpain Ⅰwere significantly increased in operation group(P<0.05). There were no significant differences in SBP and DBP betweenmetoprolol-treated group and the operation group(P>0.05). Furthermore, values of SBP and DBP were significantly higherin metoprolol-treated group than those of sham group(P<0.05). Compared with operation group, values of LVW/BW, theprotein expression and activity of Ca N m RNA and Calpain Ⅰ were significantly decreased in metoprolol group(P<0.05),which were no significant differences compared with sham group.ConclusionMetoprolol prevents myocardial hypertrophyin abdominal aorta coarctative rats, through inhibiting Calpain Ⅰ and Ca N signaling pathways.更多还原