Kisspeptin-13和Cortistatin-14对小鼠胃肠运动的影响作用研究

发布时间：2018-01-24 14:20

本文关键词： Kisspeptin-13 Cortistatin-14 胃肠运动　出处：《兰州大学》2017年硕士论文　论文类型：学位论文

【摘要】：Kisspeptin-13(Kp-13)是由KiSS基因表达的的蛋白酶解产物,含有13个氨基酸残基。研究表明,GPR54为Kp-13的受体,广泛分布于包括胃肠道在内的多种器官和组织。Kp-13具有多种生理学功能,包括抑制恶性肿瘤细胞的迁移、生殖调节作用以及内分泌调节功能等。然而,尚未有Kp-13对胃肠运动影响的研究。因此本研究讨论了中枢注射Kp-13对小鼠胃肠运动的影响。发现Kp-13(2μg)对小鼠的胃排空没有影响,但是能够明显促进小肠和结肠的运动。GPR54受体的拮抗剂Kp-234可以抑制Kp-13对胃肠运动的促进作用。体外研究发现,Kp-13在胃和小肠的离体肌条上没有作用,但是可以改变结肠环形肌和纵行肌的收缩,同时,Kp-13的这种作用能够被Kp-234拮抗。以上研究表明,Kp-13对胃肠运动的促进作用是通过激活GPR54受体实现的,表明Kp/GPR54系统可能参与胃肠运动的调节。Cortistatin-14(CST-14)是近年来被发现的一种广泛分布于中枢神经系统和外周组织的环肽,由14个氨基酸构成。研究表明,CST-14的氨基酸序列和somatostatin-14(SST-14)高度同源,并且可以结合所有的生长抑素受体。据报道,SST-14可以影响多种胃肠道功能,包括胃肠道的运动、分泌以及电解质和水分的运输等。然而,CST-14在胃肠运动中的作用尚未发现。我们的研究首次证实了CST-14对胃肠运动的影响。侧脑室注射CST-14对小鼠胃肠运动没有影响,而腹腔注射CST-14可以剂量依赖性地抑制小肠和结肠的运动。表明CST-14是通过外周神经系统来调节胃肠运动的。体外研究发现,CST-14可以引起空肠、回肠和结肠离体肌条的收缩,并且可以被SST受体的非选择性抑制剂c-SOM拮抗。之前的研究表明,胃肠道中主要包含三种SST受体(即SSTR-2,SSTR-3和SSTR-5),而CYN154806、ODN-8和BIM23056分别为它们的选择性拮抗剂。实验结果发现,CST-14在小肠和结肠中的作用可以被适当浓度的CYN154806和ODN-8抑制,但不能被BIM23056拮抗,表明CST-14的作用主要是通过激活SSTR-2和SSTR-3受体来发挥的。同时,对各种神经阻断剂进行研究发现,只有心得安可以阻断CST-14的作用,表明去甲肾上腺素能系统可能参与了CST-14对胃肠运动的调节作用。以上结果说明CST-14是通过激活肠神经系统中的SSTR-2和SSTR-3受体来抑制胃肠运动的,并且去甲肾上腺素能系统可能参与了CST-14对胃肠运动的调控。表明CST系统可能作为治疗功能性胃肠疾病的新靶点。
[Abstract]:Kisspeptin-13 Kp-13) is a proteolytic product expressed by KiSS gene and contains 13 amino acid residues. Kp-13, which is widely distributed in many organs and tissues, including gastrointestinal tract, has a variety of physiological functions, including inhibiting the migration of malignant tumor cells, reproductive regulation and endocrine regulation. There has not been any study on the effect of Kp-13 on gastrointestinal motility. Therefore, the effect of central injection of Kp-13 on gastrointestinal motility in mice was discussed. Kp-13(2 渭 g was found. There was no effect on gastric emptying in mice. But Kp-234, an antagonist that can significantly promote the movement of small intestine and colon. GPR54 receptor antagonist, can inhibit the effect of Kp-13 on gastrointestinal motility. Kp-13 has no effect on isolated strips of the stomach and small intestine, but it can change the contraction of the ring and longitudinal muscles of the colon and at the same time. This effect of Kp-13 can be antagonized by Kp-234. It is suggested that Kp-13 promotes gastrointestinal motility by activating GPR54 receptor. This suggests that the Kp/GPR54 system may be involved in the regulation of gastrointestinal motility. Cortistatin-14CST-14). It is a kind of cyclic peptide widely distributed in the central nervous system and peripheral tissues in recent years. The amino acid sequence of CST-14 was highly homologous to somatostatin-14 (SST-14). SST-14 has been reported to affect many gastrointestinal functions, including gastrointestinal motility, secretion, and the transport of electrolytes and water. The role of CST-14 in gastrointestinal motility has not been found. Our study has confirmed the effect of CST-14 on gastrointestinal motility for the first time. CST-14 injection into the lateral ventricle has no effect on gastrointestinal motility in mice. Intraperitoneal injection of CST-14 can inhibit the movement of small intestine and colon in a dose-dependent manner, suggesting that CST-14 regulates gastrointestinal motility through peripheral nervous system. CST-14 can cause contraction of isolated muscle strips of jejunum, ileum and colon and can be antagonized by c-SOM, a non-selective inhibitor of SST receptor. There are three kinds of SST receptors in gastrointestinal tract, namely SSTR-2, SSTR-3 and SSTR-5, and CYN154806. ODN-8 and BIM23056 were their selective antagonists. The role of CST-14 in small intestine and colon can be inhibited by appropriate concentration of CYN154806 and ODN-8, but can not be antagonized by BIM23056. The results suggest that the role of CST-14 is mainly through the activation of SSTR-2 and SSTR-3 receptors. At the same time, various nerve blockers have been found. Only propranolol can block the effect of CST-14. These results suggest that noradrenergic system may be involved in the regulation of gastrointestinal motility by CST-14. These results suggest that CST-14 activates SSTR-2 and SSTR-3 in the enteric nervous system. Receptors to inhibit gastrointestinal motility. Furthermore, noradrenergic system may be involved in the regulation of gastrointestinal motility by CST-14, suggesting that CST system may be a new target for the treatment of functional gastrointestinal diseases.
【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】：R96

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