Khaper N, Rigatto C, Seneviratne C, Li T, Singal P K
St Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Canada.
J Mol Cell Cardiol. 1997 Dec;29(12):3335-44. doi: 10.1006/jmcc.1997.0558.
The goal of this study was to examine whether chronic administration of propranolol offers protection against ischemia-reperfusion injury and whether it induces any change in the myocardial endogenous antioxidant enzyme activities and their gene expression. Rats were treated with propranolol (10 mg/kg/day, i.p.) for either 6 or 18 days. Forty-eight h after the last propranolol injection, isolated hearts were subjected to 60 min of global ischemia and 40 min of reperfusion. Resting tension in the control and treated groups after ischemia was 385+/-30 and 150+/-15%; and upon reperfusion was 140+/-11 and 49+/-6%, respectively, as compared to the pre-ischemic values. Recovery of the contractile function in globally ischemic hearts upon reperfusion was about 35% in the treated group as compared to about 16% in the control group at 10 and 20 min. A positive response to catecholamine was observed in hearts from propranolol group (C, 3.41+/-0.36; epi, 6.03+/-0.47 g/g) and was comparable to control hearts (C, 3.55+/-0.31; epi, 6.48+/-0.42 g/g). Myocardial antioxidants, catalase and glutathione peroxidase enzyme activities, in the treated group, prior to ischemia-reperfusion were increased by 67+/-9 and 45+/-11%, respectively, over those in controls. Superoxide dismutase activity did not show any change. The mRNA expression for the three antioxidant enzymes did not change in the hearts of the treated group as compared to control. Lipid peroxidation, both before and after the ischemia-reperfusion episode, was significantly reduced in the propranolol-treated hearts compared to the control group. Hearts studied at the end of reperfusion showed no difference in enzyme activities between treated and control groups. These data show that propranolol treatment of the animals protects against ischemia-reperfusion injury in isolated hearts in the absence of beta-blockade. Increased endogenous antioxidant enzyme activities due to propranolol treatment may have a role in this protection.
本研究的目的是考察长期给予普萘洛尔是否能预防缺血-再灌注损伤，以及它是否会引起心肌内源性抗氧化酶活性及其基因表达的任何变化。大鼠接受普萘洛尔（10mg/kg/天，腹腔注射）治疗6天或18天。在最后一次注射普萘洛尔48小时后，分离心脏并进行60分钟的全心缺血和40分钟的再灌注。与缺血前的值相比，缺血后对照组和治疗组的静息张力分别为385±30%和150±15%；再灌注时分别为140±11%和49±6%。在10分钟和20分钟时，再灌注后全心缺血心脏收缩功能的恢复在治疗组约为35%，而对照组约为16%。在普萘洛尔组的心脏中观察到对儿茶酚胺的阳性反应（C，3.41±0.36；肾上腺素，6.03±0.47g/g），且与对照心脏相当（C，3.55±0.31；肾上腺素，6.48±0.42g/g）。在缺血-再灌注前，治疗组心肌抗氧化剂、过氧化氢酶和谷胱甘肽过氧化物酶的活性分别比对照组增加了67±9%和45±11%。超氧化物歧化酶活性没有显示任何变化。与对照组相比，治疗组心脏中三种抗氧化酶的mRNA表达没有变化。与对照组相比，普萘洛尔治疗的心脏在缺血-再灌注前后的脂质过氧化均显著降低。在再灌注结束时研究的心脏显示，治疗组和对照组之间的酶活性没有差异。这些数据表明，在没有β受体阻滞的情况下，用普萘洛尔治疗动物可预防离体心脏的缺血-再灌注损伤。普萘洛尔治疗导致的内源性抗氧化酶活性增加可能在这种保护中起作用。
