蒙药苏格木勒-3汤调控内质网应激/缝隙连接蛋白抗癫痫作用及其机制研究

Epilepsy is a refractory disease threatening life health of people. In previous study, our research group found that Mongolian medicine Sugemule-3 (SM-3) decoction can effectively prevent and cure central nervous system injury of epileptic rats, and decrease the expressions of endoplasmic reticulum stress marker protein Chop and Connexin43 in rat hippocampus, which indicated that SM-3 maybe prevent and cure epilepsy through regulating endoplasmic reticulum stress pathway and connexin. But the specific functions and mechanisms should be illuminated urgently. In this project, we plan to survey the effects of SM-3 on rat/cell seizure models kindled chronically by pentylenetetrazole (PTZ) from intact animals and cellular level, discuss the specific mechanism of SM-3 in treating epilepsy through Q-PCR, WB, immunohistochemistry, flow cytometry and other molecular biology technologies, and confirm the functions of endoplasmic reticulum stress pathway and connexin in interfering process of SM-3 to epilepsy by suppressing signaling pathways and so on. The ultimate aims are to illuminate the molecular mechanisms of SM-3 in prevention and treatment of epilepsy by regulating endoplasmic reticulum stress pathway and connexin, and confirm the targets of SM-3 in curing epilepsy and improving brain injury, meanwhile combine the Mongolian medicine theory to deeply elucidate the scientific connotation of Mongolian medicine in curing epilepsy, which will lay the foundation for related research of Mongolian medicine.

癫痫病是严重威胁人们生命健康的难治性疾病。本课题组前期研究发现蒙药苏格木勒-3汤（SM-3）可有效防治癫痫大鼠中枢神经系统损伤，并能降低癫痫大鼠海马组织中内质网应激标志蛋白Chop和缝隙连接蛋白Cx43的表达。提示SM-3可能通过调控内质网应激途径及缝隙连接蛋白防治癫痫发作，但其具体作用不明。本课题拟从整体动物和细胞水平观察SM-3对PTZ慢性点燃大鼠/细胞癫痫模型的作用；通过Q-PCR、WB、免疫组化、流式细胞术等分子生物学手段探讨SM-3治疗癫痫发作的具体机制；并采用信号通路抑制剂等手段确证内质网应激途径和缝隙连接蛋白在SM-3干预癫痫中的作用。最终旨在阐明 SM-3调控内质网应激途径和缝隙连接蛋白防治癫痫发生发展的分子机制，确定SM-3治疗癫痫发作，改善脑损伤的作用靶点。并结合蒙医药理论从深层次阐释蒙医治疗癫痫病的科学内涵，为蒙医药相关研究奠定基础。

癫痫病是严重威胁人们生命健康的难治性疾病。本课题组在前期研究基础上，以蒙药苏格木勒-3（SM-3）汤治疗癫痫的作用机制为研究目标：首先在整体动物水平研究SM-3 对戊四唑（PTZ） 慢性点燃大鼠癫痫模型的作用，发现SM-3可以减弱PTZ诱发的大鼠癫痫状态，同时可以有效缓解PTZ导致大鼠学习记忆减弱行为。并初步判定可能影响了大鼠海马组织细胞的凋亡，接着在细胞水平研究SM-3 对PTZ 诱导癫痫细胞模型的作用，发现SM-3提取物可以减弱PTZ诱导细胞凋亡，在接下来的机制研究中发现在整体动物/细胞水平SM-3均可通过调节PTZ 诱导的内质网应激和缝隙连接蛋白升高而起到调控作用，通过上述研究，团队认为，SM-3临床价值较高，为了进一步探索相关机制，我们尝试探索临床难治性癫痫患者缺氧诱导因子（HIF）-1α的表达过程中MiR-153调节的调节及在全面环形RNA水平分析揭示了CircRNA-0067835 / miR-155通路在颞叶癫痫中的调节作用；为后续深入研究SM-3治疗癫痫的临床用途奠定基础。.