次黄嘌呤－内源性单胺氧化酶（MAO）抑制剂样活性的研究

Study on EndQgenous MAO-inhibitor like action of HyPoxanthine

体外实验证明，嘌呤类化合物对Ｂ－型ＭＡＯ活性有不同程度的抑制作用，其抑制强度为：次黄嘌呤＞鸟便嘌呤＞腺嘌呤＞嘌呤＞黄嘌呤＞尿酸。老龄小鼠（１８月龄）的血、脑及肝组织ＭＡＯ活性较年青小鼠（１月龄）显著升高，而上述组织中嘌呤类化合物的含量却随年龄增加而降低。老龄小鼠肝线粒体外膜ＭＡＯ提取物中次黄嘌呤含量明显低于年青小鼠，但两组ＭＡＯ中腺嘌呤含量却无明显差异。离体温孵实验证明［３Ｈ］次黄嘌呤与老龄小鼠脑和肝ＭＡＯ结合量明显高于年青小鼠。体内结合实验结果亦表明［３Ｈ］次黄嘌呤与老龄小鼠肝ＭＡＯ结合量高于年青小鼠外，并证明［３Ｈ］次黄嘌呤的结合部位是在ＭＡＯ酶蛋白上，而非在辅基上。此外，多次灌服次黄嘌呤２００ｍｇ／ｋｇ可明显抑制老龄小鼠脑ＭＡＯ－Ｂ活性，并使单胺类物质（５－ＨＴ、ＤＡ）含量明显增加。

t was found that MAO--B activitees in blood, liver and brain tissues were increased with advanced age, but thecontent Of purines (hypoxanthine,adenine, xanthine, guanine) and uric acid in the above-mentioned tissues were decreased with advanced age. The amount of hypoxanthine, released from the MAO of aged mice, was lower than that ofthe young mice. However,In vivo and in vitro experiments demonstrated that the binding amount of [3H]hypoxanthine with MAO protein in liver and brain tissues from aged mice increased as compared with young mice. However,Invivo and in vitro experiments demonstrated that the binding amount of[3H]hypoxanthine with MAO protein in liverand brain tissues from aged mice increase and the purines compounds really showed inhibiting effect on MAO-B activity in vitro. The intensities Of their activity are as follows hypoxanthine > Guanine > adenine > purine > xanthine > uricacid. In addition, the repeated administration of hypoxanthine (200mg/kg)could induce significantly inhibition ofMAO-B activity and increased the contents of 5-HT and dopamine in brain tissues of aged mice. The above results suggested that the enhancement of MAO activity was directly related to the decrease in content of hypoxanthine-endogenous inhibitors for MAO in aged mice.