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