内吗啡肽-1衍生多肽对人精子活力的影响及机制研究

发布时间：2018-05-15 11:52

本文选题：内吗啡肽-1衍生多肽 + 精子活力　；参考：《兰州大学》2017年硕士论文

【摘要】：在脑内至少存在三种阿片受体,其分别是μ-阿片受体(MOR)、δ-阿片受体(DOR)和κ-阿片受体(KOR)。同时,还发现在人类精子细胞膜上也存在这三种类型的阿片受体,并且已经有研究证明阿片类镇痛药会降低精子活力,而在临床上,确实存在一些慢性疼痛疾病的患者和癌症患者,他们需要长期服用镇痛药物。当这些特殊患者有生育要求时,我们能否提供一种镇痛效果好且对精子活力影响小的药物?方法:通过D-Ala-Gly替代2位的Pro,在N端胍基化以及对5位的Phe进行氯化修饰这三种改造方法,得到HAGDC,GAGPC,GAGDC,HAGPC这四个内吗啡肽-1衍生多肽,并对以上所有多肽的亲和活性、酶解稳定性及镇痛活性进行检测,同时检测在不同浓度下各个类似物在不同时间点对精子活力的影响,并对加入药物后的精液标本进行精子DNA碎片率检测,筛选出镇痛效果强,并且在一定的浓度时对精子活力影响不大的新型镇痛药。结果:类似物GAGPC外周镇痛活性最强,并且随着浓度增大时,可以维持精子活力,而GAGDC虽然在外周的镇痛活性也很强持续时间长,但对精子活力却有明显的抑制作用,这与GAGPC的δ-受体亲和能力相对较高有关,因为当GAGPC的浓度高时,在激活μ-受体的同时也会激动更多的δ-受体,从而减轻对精子活力的影响,以达到维持或保护精子活力的作用。结论:GAGPC是本次研究所筛选出来的镇痛活性好且对精子活力影响小的新型镇痛药物。
[Abstract]:There are at least three kinds of opioid receptors in the brain, namely 渭 -opioid receptor (Mor), 未 -opioid receptor (DORA) and 魏 -opioid receptor (KORA). These three types of opioid receptors have also been found in human sperm cell membranes, and studies have shown that opioid analgesics reduce sperm motility, while clinically, There are some chronic pain patients and cancer patients who need to take analgesic drugs for a long time. When these special patients have fertility requirements, can we provide a drug that has a good analgesic effect and has little effect on sperm motility? Methods: four endomorphine peptide-1-derived peptides were obtained by D-Ala-Gly substitution for 2-position Pros, N-terminal guanidylation and chlorination modification of 5-position Phe, and their affinity to all the above peptides were obtained. The stability of enzymatic hydrolysis and analgesic activity were detected. The effects of analogue at different concentrations on sperm motility at different time points were also detected. The sperm DNA fragment rate of semen samples after adding drugs was detected and the analgesic effect was found to be strong. And at a certain concentration of sperm motility of a new type of analgesics. Results: the peripheral analgesic activity of GAGPC was the strongest, and the sperm motility could be maintained with the increase of the concentration of GAGDC. Although the analgesic activity of GAGDC in the peripheral area was also very strong for a long time, it had obvious inhibitory effect on sperm motility. This is related to the relatively high affinity of the 未 -receptor of GAGPC, because when the concentration of GAGPC is high, it activates the 渭 -receptor and excites more 未 -receptors, which reduces the effect on sperm motility and achieves the function of maintaining or protecting sperm motility. Conclusion: Genus GAGPC is a new analgesic drug with good analgesic activity and little effect on sperm motility.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R402

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