基于CNP-cGMP信号通路研究疏肝健脾法对FD肝郁脾虚证大鼠胃窦平滑肌及ICC的干预机制

Functional dyspepsia (FD) is a disease with gastrointestinal motility disorder and accompanied by mental disorders. There are many overlapping symptoms , changeable or convertible and recurrent, difficult to cure and so on. The pathogenesis of FD is complex diversified, gastrointestinal motility disorder is the major pathophysiological basis of FD , while traditional Chinese medicine believe that liver-depression and spleen-deficiency is the main crux of gastrointestinal motility disorder. The recent study found that CNP-cGMP signal transduction pathway is closely associated with gastrointestinal motility disorders. Based on previous research , we put forward a hypothesis based on our previous research: gastrointestinal motility disorders of FD with liver-depression and spleen-deficiency syndrome may be closely related to the CNP-cGMP signal transduction pathway, through reducing the contraction of gastric smooth muscle and inhibiting ICC pacemaker current. Using the liver-soothing spleen-strengthening method (Shuwei Decotion) ,to establish FD of liver-depression and spleen-deficiency syndrome large rat and cell model as study objects by composite causes , applied multiple technology means such as Western-blot, RT-PCR, radiation immune method and total focused microscope and so on, from the CNP-cGMP signal transduction pathway regulating function of smooth muscle contraction ,ICC pacemaker current way to study the influence of liver-soothing spleen-strengthening method(Shuwei Decotion) on FD liver-depression and spleen-deficiency syndrome, providing new ideas and theoretical basis for prevention and treatment of FD.

功能性消化不良（FD）是以胃肠动力障碍为主并多伴有心理精神障碍的一种疾病，有多种症状重叠、多变或相互转换以及反复发作、较难治愈等特点。FD发病机制复杂多元化，胃肠动力障碍是FD的主要的病理生理学基础，而中医认为肝郁脾虚是导致FD胃肠动力障碍的主要症结所在。而近期研究发现CNP-cGMP信号转导途径与胃肠动力障碍密切相关。我们基于前期研究基础提出假说： FD肝郁脾虚证胃肠动力障碍与CNP-cGMP信号转导途径降低胃平滑肌收缩活动和抑制ICC起搏电流密切相关；采用疏肝健脾法（舒胃汤），以复合病因建立FD肝郁脾虚证动物及细胞模型为受试对象，运用Western-blot、RT-PCR、放射免疫法、激光共聚焦显微镜等技术，从CNP-cGMP信号通路调节平滑肌收缩功能、ICC起搏电流途径研究疏肝健脾法（舒胃汤）对FD肝郁脾虚证胃肠动力、胃电节律的影响，为防治FD提供新思路和理论依据。

功能性消化不良（FD）是以胃肠动力障碍为主并多伴有心理精神障碍的一种疾病，有多种症状重叠、多变或相互转换以及反复发作、较难治愈等特点。胃肠动力障碍是FD的主要的病理生理学基础，而中医认为肝郁脾虚是导致FD胃肠动力障碍的主要症结所在。我们基于前期研究基础提出假说： FD肝郁脾虚证胃肠动力障碍与CNP-cGMP信号转导途径降低胃平滑肌收缩活动和抑制ICC起搏电流密切相关；采用疏肝健脾法（舒胃汤），以复合病因建立FD肝郁脾虚证动物及细胞模型为受试对象，运用Western-blot、RT-PCR、放射免疫法、激光共聚焦显微镜等技术，从CNP-cGMP信号通路调节平滑肌收缩功能、ICC起搏电流途径研究疏肝健脾法（舒胃汤）对FD肝郁脾虚证胃肠动力、胃电节律的影响。本研究发现：FD肝郁脾虚证模型大鼠平滑肌细胞膜CNP-cGMP信号通路上cGMP、pGC、CNP、NPR-B表达升高，使平滑肌细胞钙离子浓度下降，平滑肌收缩能力减弱；FD肝郁脾虚证模型大鼠ICCs 细胞膜CNP-cGMP信号通路上NPR-B、pGC和cGMP表达升高，使PKG诱导的磷酸酶活性增加，从而使VGPC、VGCCs和CACCs的电流密度减少，从而证实了FD肝郁脾虚证胃肠动力障碍与CNP-cGMP信号转导途径降低胃平滑肌收缩活动和抑制ICC起搏电流密切相关。舒胃汤改善FD大鼠胃肠动力，加快模型大鼠胃排空和小肠推进，其途径是通过下调平滑肌细胞膜CNP-cGMP信号通路上cGMP、pGC、CNP、NPR-B蛋白含量，使平滑肌细胞钙离子浓度升高，从而恢复平滑肌收缩能力；舒胃汤能下调ICCs 细胞膜CNP-cGMP信号通路上NPR-B、pGC和cGMP，使PKG诱导的磷酸酶活性降低，从而使VGPC、VGCCs和CACCs的电流密度增加，促进胃肠动力，从而阐释了肝健脾法（舒胃汤）通过CNP-cGMP信号通路调节平滑肌收缩功能、ICC起搏电流途径治疗肝郁脾虚证胃肠动力障碍、胃电节律紊乱。