知母皂甙元对老年大鼠脑M受体的调节

The Regulatory Action of ZMS on The Distribution and Content of Brain M-receptors and Its M_1 Subtype in Aged Rats: Studied by Autoradiographic Technique

以３Ｈ－ＱＮＢ和３Ｈ－ＰＺ为放射配基，用放射自显影技术分别测定大鼠大脑皮层、海马、纹状体的Ｍ受体及Ｍ１受体亚型的相对含量。平行实验表明，老年组三个部位的Ｍ及Ｍ１密度均比青年大鼠相应部位的受体密度显著降低；衰老晚期大鼠受体的降低比衰老早期大鼠更显著。衰老早期及晚期的大鼠用知母皂甙元（ＺＭＳ）后，能明显提高相应皮层、海马降低的Ｍ及Ｍ１受体数，有显著性意义；对衰老早期大鼠纹状体部位的Ｍ及Ｍ１受体也有显著提高。三个脑区中，衰老大鼠Ｍ受体的变化和Ｍ１受体亚型的变化趋势基本一致，认为Ｍ受体数的降低主要是Ｍ１受体亚型数减少引起，并且随着衰老进程的发展，降低的程度也愈加明显。ＺＭＳ提高Ｍ受体数，可能是通过提高Ｍ１受体亚型的密度来实现。

In order to study the changes of total M-receptors in different brain areas of aged rats, an autoradiographic technique (ARG) was established using a computerized densitometer to quantitate the grain densities of different brain areas after in situ binding of 3H-QNB with brain slices. Experiments on aged rats revealed that the M cholinergic receptor densities of striatum, hippocampus and cerebral cortex were significantly lower than those of young controls. When ZMS treated and untreated aged rats were compared, the densities of M-receptors of the above areas were found to be significantly higher in ZMS treated rats than untreated animals. Moreover, parallel experiments have been carried out to study the quantitative distribution of M1 receptor subtype in different brain areas using 3H-Pirenzipine as the radiolabelled probe. The results indicated that the changes were similar as the results obtained from total M-receptors in aged animals compared with young rats, and ZMS treated aged rats compared with untreated aged rats. Thus, it is thought that the M1 receptor subtype is vulnerable to aging, and its density is significantly decreased in the aged, while ZMS is able to maintain the M-receptor density at normal level in model animals mainly by elevating the M1 receptor density.