万生芳 李雅琪 王晓丽

摘要：目的 觀察金芪枳术汤对糖尿病胃轻瘫（DGP）GK大鼠胃动力的影响，探讨其作用机制。方法 80只雄性GK大鼠随机选取12只作为正常组，其余68只给予高糖高脂饲料不规则喂养8周制备DGP模型，成模大鼠随机分为模型组、阳性药组和金芪枳术汤低、中、高剂量组，干预12周，测定胃内色素残留率，ELISA检测血浆多巴胺（DA）、乙酰胆碱（ACh）、5-羟色胺（5-HT）含量，HE染色观察胃窦组织病理变化，透射电镜观察胃窦组织黏膜层超微结构，Western blot检测胃窦组织RhoA、ROCK1、ROCK2蛋白表达。结果 与正常组比较，模型组胃内色素残留率升高，DA、ACh、5-HT含量降低，RhoA、ROCK1、ROCK2蛋白表达降低（P<0.01）；与模型组比较，阳性药组和金芪枳术汤高剂量组胃内色素残留率降低，DA、ACh、5-HT含量明显升高，RhoA、ROCK1、ROCK2蛋白表达明显升高（P<0.05，P<0.01），胃窦组织病理变化和黏膜层超微结构明显改善；与阳性药组比较，金芪枳术汤高剂量组胃内色素残留率、DA含量及RhoA、ROCK1、ROCK2蛋白表达差异均无统计学意义（P>0.05）；与金芪枳术汤低剂量组比较，金芪枳术汤高剂量组胃内色素残留率明显降低，DA、ACh、5-HT含量明显升高，RhoA、ROCK1、ROCK2蛋白表达明显升高（P<0.05，P<0.01）。结论 金芪枳术汤能提高DGP大鼠胃动力，促进胃排空，改善和修复胃窦组织黏膜层损伤，这可能与其调节RhoA/ROCK信号通路蛋白表达有关。

关键词：糖尿病胃轻瘫；金芪枳术汤；多巴胺；乙酰胆碱；5-羟色胺；RhoA/ROCK信号通路

DOI：10.3969/j.issn.1005-5304.2018.09.014

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2018）09-0056-05

Abstract： Objective To investigate the effects of Jinqi Zhizhu Decoction （JQZZD） on gastric motility of GK rats with diabetic gastroparesis （DGP）； To discuss its mechanism of action. Methods 12 out of 80 male GK rats were randomly selected as normal group， and others were induced to be DGP model by irregular feeding with high sugar and high fat diet for 8 weeks. The model rats were randomly divided into model group， positive medicine group， JQZZD low-， medium-， and high-dose groups. All rats were given continuous intragastric administration for 12 weeks. The residual rate of pigment in stomach was detected and calculated. The concentration of DA， ACh and 5-HT in plasma were detected by ELISA. The morphological changes of gastric antrum were observed by HE staining. The ultrastructure of mucous layer of gastric antrum was observed by transmission electron microscope. The protein expressions of RhoA， ROCK1 and ROCK2 were detected by Western blot. Results Compared with normal group， the residual rate of pigment in model group increased， while DA， ACh and 5-HT， relative amount of protein expressions of RhoA， ROCK1 and ROCK2 decreased （P<0.01）. Compared with model group， the residual rate of pigment in positive medicine group and JQZZD high-dose group decreased， while DA， ACh and 5-HT， relative amount of protein expressions of RhoA， ROCK1 and ROCK2 increased （P<0.05， P<0.01）， and morphological changes and ultrastructure of mucous layer obviously improved. There was no significant differences in the residual rate of pigment， DA content and protein expressions of RhoA， ROCK1 and ROCK2 between positive medicine group and JQZZD high-dose group （P>0.05）. Compared with JQZZD low-dose group， the residual rate of pigment in JQZZD high-dose group decreased， while DA， ACh and 5-HT， relative amount of protein expressions of RhoA， ROCK1 and ROCK2 increased （P<0.05， P<0.01）. Conclusion JQZZD may improve gastric motility， promote gastric emptying， and improve and repair damage of mucous membrane in the gastric antrum. All of these may be related to regulating protein expressions of RhoA/ROCK signal pathway.

Keywords： diabetic gastroparesis； Jinqi Zhizhu Decoction； dopamine； ACh； 5-HT； RhoA/ROCK signaling pathway

糖尿病胃轻瘫（diabetic gastroparesis，DGP）是糖尿病（diabetes mellitus，DM）消化道慢性并发症之一，其发病率高。DGP的发病机制复杂，与胃神经病变、胃平滑肌细胞受损等因素有关，其主要病理特征和核心环节是平滑肌细胞受损，RhoA/ROCK信号通路是平滑肌收缩调节的重要机制，RhoA是Ras同源物基因组成员之一，RhoA活化后引起一系列下游效应器激活，促进平滑肌收缩。多巴胺（DA）、乙酰胆碱（ACh）和5-羟色胺（5-HT）等神经递质对于胃肠道平滑肌的收缩均有明显的兴奋作用。本实验以DGP大鼠为研究对象，观察金芪枳术汤对DGP大鼠胃内色素残留率，DA、ACh和5-HT等神经递质活性，胃窦黏膜细胞超微结构及胃窦组织RhoA/ROCK信号通路相关因子RhoA、ROCK1、ROCK2蛋白表达的影响，探讨其促进胃动力的作用机制。……