大鼠心肌β-肾上腺素受体发育的研究

A developmental study on myocardial β adrenergic receptor in rats

目的探讨发育因素对大鼠心肌β肾上腺素受体（βＡＲ）的影响。方法应用配基结合、酶活性测定，测定不同年龄段Ｗｉｓｔａｒ大鼠心肌βＡＲ密度、受体亚型、腺苷酸环化酶（ＡＣ）活性和对βＡＲ激动剂———异丙肾上腺素反应性以及低甲状腺素大鼠心肌βＡＲ密度。结果大鼠出生时心肌βＡＲ密度平均为１４．３ｆｍｏｌ／ｍｇ（蛋白），成年后平均为３１．６ｆｍｏｌ／ｍｇ（蛋白），心肌βＡＲ密度随年龄的增长而增加（Ｆ值为２３．４６，Ｐ＜０．０１）；β１／β２ＡＲ亚型相对比值，出生时为５１／４９，成年为６０／４０；心肌ＡＣ对βＡＲ激动剂———异丙肾上腺素的反应性，出生时为７６ｐｍｏｌ·ｍｇ－１·ｍｉｎ－１，成年为１２６ｐｍｏｌ·ｍｇ－１·ｍｉｎ－１，各年龄段的差异有显著意义（Ｆ值为８９．００，Ｐ＜０．０１）；ＡＣ基础活性和ＡＣ对ＡＣ激动剂Ｆｏｒｓｋｏｌｉｎ的反应性，各年龄段没有差异；β１ＡＲ拮抗剂抑制成年大鼠心肌ＡＣ对异丙肾上腺素的反应性，β２ＡＲ拮抗剂抑制新生和发育早期大鼠心肌ＡＣ对异丙肾上腺素的反应性；血清甲状腺素减低可使生后１周和成年大鼠心肌βＡＲ密度下降。结论大鼠心肌βＡＲ密度、β１／β２ＡＲ亚型比例、β?

Objective To study the effect of developmental factors on β adrenergic receptor (AR) and its regulatory role in Wistar rat myocardium. Methods With the methods of ligand binding and enzyme activity measurement, β AR density, receptor subtypes, myocardial adenylate cyclase (AC) activity, its age related responsiveness to β AR agonist isoprenalin, and myocardial β AR density were measured in rats at different age stages. Also, myocardial β AR density was detected in hypothyroxin rats. Results Myocardial β AR density of rats was 14.3fmol/mg protein at birth, and 31.6 fmol/mg protein in adult. It increased with age ( F =23.46, P < 0.01). Relative ratio of β 1/β 2 AR was 51/49 at birth, and 60/40 in adult. The responsiveness of myocardial AC to β AR agonist isoprenalin was 76 pmol·mg -1 ·min -1 at birth and 126 pmol·mg -1 ·min -1 in adult ( F = 89.00, P <0.01). There was no difference in basic AC activity and responsiveness to AC agonist forskolin between rats at birth and in adult. Beta 1 antagonist inhibited the responsiveness of AC to isoprenalin in adult rats, while β 2 AR antagonist inhibited the responsiveness of AC to isoprenalin in newborn and young rats. Serum hypothyroxin decreased myocardial β AR densities in the newborn and adult rats. Conclusion Beta AR density, relative ratio of its subtypes and β AR regulatory effect on myocardial AC were all influenced by developmental factors.