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Cortistatin-14 在小鼠胃肠道动力中的作用。

The role of Cortistatin-14 in the gastrointestinal motility in mice.

机构信息

Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, China.

Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, China.

出版信息

Pharmacol Rep. 2018 Apr;70(2):355-363. doi: 10.1016/j.pharep.2017.09.004. Epub 2017 Sep 18.

Abstract

BACKGROUND

This study aimed to investigate the functional roles of Cortistatin-14 (CST-14) in the gastrointestinal (GI) motility.

METHODS

For in vivo study, mice were randomly divided into control, ip injected CST-14 (0.1, 0.5, 1, 5, 10mg/kg)+control group, icv injected CST-14 (5μg)+control group, dextran sulfate sodium-induced colitis group, CST-14+colitis group, castor oil-induced diarrhea group, CST-14+diarrhea group. We carried out these experiments by quantitative real-time PCR, GI transit, bead expulsion and fecal pellet output. For in vitro study, effects of CST-14 were investigated in the longitudinal and circular muscle contractions of jejum, ileum, and colon.

RESULTS

In vivo, the expression of CST-14 mRNA was significantly decreased in the colon of colitis mice and CST-14 significantly inhibited GI transit rate in colitis mice, and delayed the emergence of liquid feces in castor oil-induced diarrhea mouse model. Additionally, ip injection of CST-14, but not icv injected, remarkably inhibited GI transit, bead expulsion and fecal pellet output in mice. In vitro assays, CST-14 (10M) could relax the rhythms of the longitudinal muscles and circular muscles of the jejunum, ileum and colon of mice. The further study indicated that the roles of CST-14 in mouse GI motility were significantly reversed by c-SOM (sstr1-5 antagonist), especially sstr2 and sstr3 and propranolol (β-adrenoceptor blocker), suggesting that somatostatin system and noradrenaline system were involved in the inhibiting effects of CST-14 in GI.

CONCLUSION

Such inhibiting effects imply that CST-14 system in gastrointestinal motility might be a new target for treatment of GI tract disorder.

摘要

背景

本研究旨在探讨 Cortistatin-14(CST-14)在胃肠道(GI)运动中的功能作用。

方法

在体内研究中,将小鼠随机分为对照组、CST-14(0.1、0.5、1、5、10mg/kg)+对照组、CST-14(5μg)+对照组、葡聚糖硫酸钠诱导的结肠炎组、CST-14+结肠炎组、蓖麻油诱导的腹泻组、CST-14+腹泻组。我们通过定量实时 PCR、GI 转运、珠排出和粪便颗粒输出来进行这些实验。在体外研究中,研究了 CST-14 对空肠、回肠和结肠纵肌和环肌收缩的影响。

结果

在体内,结肠炎小鼠结肠 CST-14 mRNA 的表达明显降低,CST-14 显著抑制结肠炎小鼠的 GI 转运率,并延迟蓖麻油诱导的腹泻小鼠模型中液体粪便的出现。此外,CST-14(10M)的腹腔注射而不是脑室内注射,显著抑制了小鼠的 GI 转运、珠排出和粪便颗粒输出。体外试验表明,CST-14 可使小鼠空肠、回肠和结肠的纵肌和环肌节律松弛。进一步的研究表明,CST-14 在小鼠 GI 运动中的作用被 c-SOM(sstr1-5 拮抗剂)显著逆转,特别是 sstr2 和 sstr3 和普萘洛尔(β-肾上腺素受体阻滞剂),提示生长抑素系统和去甲肾上腺素系统参与了 CST-14 在 GI 中的抑制作用。

结论

这种抑制作用表明,CST-14 系统在胃肠道动力中可能是治疗胃肠道疾病的新靶点。

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