中华老年心脑血管病杂志

目的 探究有氧运动联合红花黄素对高血压大鼠心血管重构、心肌细胞离子通道以及转化生长因子β(transforming growth factor β,TGF-β)/SMAD家族成员(SMAD family member, Smad)信号通路的影响。方法 选择正常血压大鼠8只作为对照组，将自发性高血压大鼠32只采用随机数字法分为高血压组、有氧运动组(有氧运动训练)、红花黄素组(50 mg/kg红花黄素灌胃)、联合干预组(有氧运动训练+红花黄素灌胃)，每组8只。采用无创大鼠尾动脉血压测量仪检测收缩压、舒张压和平均动脉压(mean arterial pressure,MAP)；测量心脏总质量以及左心室质量，计算心脏质量指数(heart weight index,HWI)及左心室质量指数(left ventricular mass index,LVMI)；膜片钳技术检测L型钙通道电流(L-type calcium channel current,I_Ca-L)密度、瞬时外向钾电流(transient outward potassium current,I_to)密度；苏木精-伊红染色和Masson染色观察心肌组织病理程度；Western blot法分析TGF-β/Smad信号通路关键蛋白表达。结果 与对照组比较，高血压组、有氧运动组、红花黄素组及联合干预组收缩压、舒张压和MAP、HWI、LVMI、I_Ca-L、TGF-β₁、磷酸化Smad2、磷酸化Smad3表达明显升高，I_to表达明显降低，高血压组、有氧运动组、红花黄素组Smad7表达明显降低，差异有统计学意义(P<0.05)；与高血压组比较，有氧运动组、红花黄素组以及联合干预组收缩压、舒张压和MAP、HWI、LVMI、I_Ca-L、TGF-β₁、磷酸化Smad2、磷酸化Smad3表达明显降低，I_to、Smad7表达明显升高，差异有统计学意义(P<0.05)；与有氧运动组和红花黄素组比较，联合干预组收缩压[(135.82±5.47)mm Hg(1 mm Hg=0.133 kPa) vs(152.45±6.23)mm Hg、(148.72±5.89) mm Hg,P<0.05]、舒张压[(88.45±3.78)mm Hg vs(98.34±4.56)mm Hg、(96.67±4.32)mm Hg,P<0.05]和MAP[(104.91±4.63)mm Hg vs(116.71±5.42)mm Hg、(114.36±5.18)mm Hg,P<0.05]明显降低；联合干预组HWI、LVMI、I_Ca-L、TGF-β₁、磷酸化Smad2、磷酸化Smad3表达明显低于有氧运动组和红花黄素组，I_to、Smad7表达明显高于有氧运动组和红花黄素组，差异有统计学意义(P<0.05)。结论 有氧运动联合红花黄素能够降低血压、减轻心脏重构、调节心肌细胞离子通道功能以及抑制TGF-β/Smad信号通路过度激活。

Objective To investigate the effects of aerobic exercise(AE) combined with safflower yellow(SY) on cardiovascular remodeling, ion channels in cardiomyocytes, and the transforming growth factor β(TGF-β)/Smad signaling pathway in hypertensive rats. Methods Eight normotensive rats were selected as the control group. Thirty-two spontaneously hypertensive rats(SHRs) were randomly divided into a hypertensive group, an AE group(AE training), a safflower yellow group(gavage administration of 50 mg/kg SY), and combined intervention group(aerobic exercise training + SY), with 8 rats in each group. A non-invasive rat tail artery blood pressure monitor was used to measure systolic blood pressure(SBP), diastolic blood pressure(DBP), and mean arterial pressure(MAP). The total heart weight and left ventricular weight were measured to calculate heart weight index(HWI) and left ventricular weight index(LVWI). Patch-clamp technique was employed to detect the density of L-type calcium channel current(I_Ca-L) and transient outward potassium current(I_to). HE staining and Masson staining were performed to observe the pathological changes in myocardial tissue. Western blot analysis was applied to detect the expression of key proteins in the TGF-β/Smad signaling pathway. Results Compared with the control group, the SBP, DBP, MAP, HWI, LVWI, amplitude of I_Ca-L density, and expression levels of TGF-β₁, p-Smad2, and p-Smad3 were significantly increased, while the I_to expression was significantly decreased in the hypertensive group, AE group, SY group, and combined intervention group; the Smad7 expression was obviously decreased in the other three groups except the combined intervention group(P<0.05). The AE group, SY group, and combined intervention group exhibited significantly reduced SBP, DBP and MAP, HWI, LVWI, amplitude of I_Ca-L density, and expression of TGF-β₁, p-Smad2, and p-Smad3, whereas elevated I_to density and Smad7 expression when compared with the hypertensive group(P<0.05). Combined intervention of AE and SY resulted in more significant decreases in SBP [135.82±5.47 mm Hg(1 mm Hg=0.133 kPa) vs 152.45±6.23 mm Hg and 148.72±5.89 mm Hg, P<0.05], DBP(88.45±3.78 mm Hg vs 98.34±4.56 mm Hg and 96.67±4.32 mm Hg, P<0.05) and MAP(104.91±4.63 mm Hg vs 116.71±5.42 mm Hg and 114.36±5.18 mm Hg, P<0.05), HWI, LVWI, amplitude of I_Ca-L density, and the expression levels of TGF-β₁, p-Smad2, and p-Smad3, as well as more remarkable increases in I_to density and Smad7 expression in comparison with the AE group and the SY group(P<0.05). Conclusion Combination of AE and SY can reduce blood pressure, alleviate cardiac remodeling, regulate the function of myocardial cell ion channels, and inhibit the overactivation of the TGF-β/Smad signaling pathway.