功能性消化不良肝胃不和证大鼠胃RhoA/ROCK信号通路变化及四磨汤干预机制

Clinical observation showed that patients in liver-stomach disharmony functional dyspepsia (FD) suffered from obvious stomach dynamic obstacles. Researches indicated that gastric motility was related to calcium sensitization mechanism. RhoA/ROCK signaling pathway involved in calcium sensitization mechanism. While the relationship between gastric dynamic disorders in liver-stomach disharmony FD and RhoA/ROCK signaling pathway was unclear. Our study found that the expression of RhoA and ROCK declined in stomach and gastric motility was remarkably weakened for liver-stomach disharmony FD rats. Simo decoction is the Chinese medicine for Hewei Jiangni and can improve the stomach dynamic obstacles of FD. Gastric motility and the expression of RhoA and ROCK were recovered after simo decoction treated. Besides Y27632 that was an inhibitor for the RhoA/ROCK signaling pathway blocked the enhancement of gastric smooth muscle contraction caused by simo decoction (see our work). Based on the previous study, we chose rat FD models and gastric smooth muscle cells with ROCK down-regulated expression as objectives. We will investigate the correlation between liver-stomach disharmony FD and RhoA/ROCK signaling pathway and intervention of simo decoction using the method of electrophysiology, cytobiology and molecular biology. This study will provide the complement for the pathogenesis of FD gastric dynamic disorders. And it will clarify mechanism between RhoA/ROCK signaling pathway and simo decoction improvement for FD. Furthermore, it will provide experimental basis for further application of simo decoction in clinical Chinese medicine integrated with western medicine.

临床观察显示功能性消化不良（FD）肝胃不和证患者存在明显胃动力障碍。研究表明胃动力与钙敏化机制密切相关，RhoA/ROCK信号通路参与钙敏化过程，但目前尚无该信号通路与FD肝胃不和证胃动力障碍关系的报道。研究发现FD肝胃不和证大鼠胃动力明显减弱且胃组织RhoA和Rock表达下降；四磨汤是改善FD胃动力障碍的中药方剂，有和胃降逆功效，能改善胃动力且恢复RhoA和Rock表达；RhoA/ROCK信号通路抑制剂Y27632阻断四磨汤引起的胃平滑肌肌条收缩增强的作用（工作基础）。本研究拟以FD肝胃不和证大鼠和ROCK低表达胃平滑肌细胞为研究对象，通过电生理、细胞生物及分子生物技术探讨FD肝胃不和证RhoA/ROCK信号通路变化及四磨汤对胃动力障碍干预作用。补充FD肝胃不和证胃动力障碍的病机，阐明RhoA/ROCK信号通路参与四磨汤改善FD肝胃不和证胃动力障碍的机制，为四磨汤中西医临床应用提供依据。

功能性消化不良（FD）肝胃不和证患者存在明显胃动力障碍。四磨汤是改善FD胃动力障碍的中药方剂，有和胃降逆功效，能改善胃动力。胃动力与钙敏化机制密切相关，RhoA/ROCK信号通路参与钙敏化过程，但目前尚无该信号通路与FD肝胃不和证胃动力障碍关系的报道。本研究构建FD肝胃不和证大鼠模型和ROCK低表达胃平滑肌细胞模型，采用分子生物学实验、免疫组化实验、细胞实验及电生理实验探讨了FD肝胃不和证RhoA/ROCK信号通路变化及四磨汤对胃动力障碍干预作用。本研究结果显示，FD肝胃不和证大鼠胃组织和ROCK低表达胃平滑肌细胞模型中RhoA、ROCK、MYPT1和CPI-17 基因及蛋白表达明显降低；四磨汤干预后，RhoA/ROCK信号通路分子的基因和蛋白表达都明显改善；四磨汤能改善Y27632对胃肌条收缩的抑制作用。综上述，阐明FD肝胃不和证大鼠胃内RhoA/ROCK信号通路下调；而四磨汤上调RhoA/ROCK信号通路进而干预FD肝胃不和证胃动力障碍。该研究补充FD肝胃不和证胃动力障碍的病机，阐明RhoA/ROCK信号通路参与四磨汤改善FD肝胃不和证胃动力障碍的机制，为四磨汤中西医临床应用提供依据。