天津医药

天津医药 ›› 2022, Vol. 50 ›› Issue (7): 693-697.doi: 10.11958/20212756

• 实验研究 • 上一篇    下一篇

罗替加肽抑制糖尿病大鼠胃平滑肌自主收缩运动的实验研究

孙海贝，包伊特格乐，张默函   

  1. 延边大学医学院（邮编133000）
  • 收稿日期:2021-12-15 修回日期:2022-03-10 出版日期:2022-07-15 发布日期:2022-07-15
  • 基金资助:
    国家自然科学基金资助项目（82060154）

Inhibitory effect of Rotigaptide on autonomic contraction of gastric smooth muscle in diabetic rats

SUN Haibei, BAO Yitegele, ZHANG Mohan   

  1. Yanbian University College of Medicine, Yanji 133000, China
  • Received:2021-12-15 Revised:2022-03-10 Published:2022-07-15 Online:2022-07-15

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摘要： 目的　探讨罗替加肽对糖尿病大鼠胃平滑肌自主收缩运动的影响及机制。方法　以链脲佐菌素诱导制备糖尿病大鼠模型，实验分为正常对照组和模型组。离体肌条实验观察罗替加肽处理前后2组大鼠胃平滑肌自主收缩运动的变化；Western blot法检测正常对照组、模型组及模型组经罗替加肽处理后（模型+罗替加肽组）的胃平滑肌组织膜蛋白和浆蛋白中连接蛋白43（Cx43）、蛋白激酶C（PKCα）的表达以及膜蛋白中p-Cx43 Ser368及p-PKCα Thr497的表达。结果　与正常对照组比较，模型组胃平滑肌自主收缩运动的振幅和频率均降低（均P＜0.05）。正常对照组与罗替加肽处理后（正常对照+罗替加肽组）比较胃平滑肌自主收缩运动振幅和频率无变化；罗替加肽处理后（模型+罗替加肽组）的胃平滑肌自主收缩运动振幅和频率较处理前（模型组）降低（均P＜0.05）。与正常对照组比较，模型组膜蛋白Cx43含量增加，浆蛋白Cx43含量降低，Cx43的膜浆比与膜蛋白p-Cx43 Ser368含量均增加（均P＜0.05）；模型+罗替加肽组与模型组相比，膜蛋白Cx43含量降低，浆蛋白Cx43含量增加，Cx43的膜浆比降低（P＜0.05）。与正常对照组比较，模型组膜蛋白PKCα含量降低，浆蛋白PKCα含量增加，PKCα的膜浆比及膜蛋白p-PKCα Thr497含量均降低（P＜0.05）；模型+罗替加肽组与模型组相比，膜蛋白p-PKCα Thr497含量增加（P＜0.05）。结论　罗替加肽可通过PKCα-Cx43通路下调缝隙连接数量及缝隙连接半通道开放率，抑制糖尿病大鼠胃平滑肌自主收缩运动。

关键词: 糖尿病, 肌, 平滑, 胃, 肌收缩, 连接蛋白43, 蛋白激酶Cα, 大鼠, Sprague-Dawley, 罗替加肽

Abstract: Objective　To discuss the effect and mechanism of Rotigaptide on the autonomic contractile movement of gastric smooth muscle in diabetic rats. Methods　The diabetic rat model (DM) was induced by streptozotocin (STZ). SD rats were divided into the control group and the DM group. In vitro muscle strip experiment was performed to observe changes of the autonomic contractile movement of the gastric smooth muscle before and after treatment with Rotigaptide in each group. Western blot assay was used to detect expression levels of Cx43 and PKCα in membrane protein and pulp protein, p-Cx43 Ser368 and p-PKCα Thr497 in gastric smooth muscle tissue of the control group, the DM group and the Rotigaptide group. Results　Compared with the control group, the amplitude and frequency of autonomic contraction in gastric smooth muscle contraction were decreased in the DM group (P＜0.05). In the control group, there were no changes in amplitude and frequency of autonomic contraction in gastric smooth muscle after treatment with Rotigaptide. In the DM group, after treatment with Rotigaptide, the amplitude and frequency of autonomic contraction in gastric smooth muscle contraction were significantly reduced (P＜0.05). Compared with the control group, the Cx43 content of membrane protein was increased, the Cx43 content of pulp protein was decreased, the membrane Cx43/pulp Cx43 ratio increased, and the p-Cx43 Ser368 content of membrane protein was increased in the DM group (P＜0.05). Compared with the DM group, the Cx43 content of membrane protein was decreased (P＜0.05), the Cx43 content of pulp protein was increased and the membrane Cx43/pulp Cx43 ratio was decreased in the Rotigaptide group (P＜0.05). Compared with the control group, the content of membrane protein PKCα was decreased, the content of pulp protein PKCα was increased and the membrane PKCα/pulp PKCα ratio was decreased in the DM group (P＜0.05). Compared with the DM group, the content of membrane protein p-PKCα Thr497 was increased in the Rotigaptide group (P＜0.05). Conclusion　Rotigaptide inhibits autonomic contraction of gastric smooth muscle in diabetic rats by down-regulating the number and the opening rate of gap junction by PKCα-Cx43 pathway activity.

Key words: diabetes mellitus, muscle, smooth, stomach, muscle contraction, connexin 43, protein kinase C-alpha, rats, Sprague-Dawley, Rotigaptide