基于c-fos介导MAPK信号通路探讨梓醇抗卵巢衰退作用机制

Catalpol is a active component in Rehmannia Root, and has extensive pharmacological effects and abundant sources. At present, catalpol’s research concentrated on the treatment of neurological diseases and its neuroprotective mechanism. Applicants for the first time confirm the ovarian aging resistance effects of catalpol by granular cell training platform and natural aging rats model, and increasing expression of IGF-1 and c - fos mRNA in the preliminary experiment. The important control factor in MAPK signal pathway of IGF-1 is c - fos. To this object, ovarian tissue of early-aging mice and GC cells were used as the research object. The effect of catalpol on expression and phosphorylation levels of the MAPK signaling pathway and the upstream and downstream gene and protein of c-fos were measured. So as to provide new experimental data support for catalpol treatment of ovarian function decline disease .

梓醇作为中药活性化合物，其研究主要集中在在神经系统疾病治疗及神经保护机制上，申请人明确了它的抗卵巢功能衰退活性，并在前期实验中证实其能升高早老大鼠卵巢组织IGF-1的表达，升高c-fos mRNA的表达。鉴于c-fos是IGF-1信号通路中主要途径——MAPK信号通路中的重要调控因子，为了探明梓醇在卵巢组织中通过c-fos介导的抗卵巢衰退作用机制，申请人以早老大鼠卵巢组织、离体卵巢颗粒细胞为研究对象，在不同程度凋亡破坏及有无梓醇存在条件下，分别考察梓醇对早老大鼠卵巢组织及卵巢颗粒细胞中MAPK信号转导途径的影响、梓醇对c-fos及其上下游元件的基因及蛋白的影响，阐明c-fos基因表达在卵巢功能衰退发病中的生物学效应，初步探讨梓醇以c-fos为靶标的抗卵巢功能衰退衰老作用机理。

梓醇作为中药活性化合物，本研究首先通过早老大鼠模型考察梓醇作用前后卵巢形态及脏器系数、雌孕激素水平、凋亡情况、MAPK 信号转导通路（JNK、p38MAPK、ERK1/2）蛋白表达及磷酸化水平的变化，可见梓醇能在体抑制p38、JNK磷酸化，抑制ERK磷酸化，上调衰老模型大鼠卵巢组织生理生化指标含量，从而改善卵巢分泌雌孕激素能力，对抗大鼠卵巢系统衰老。为了进一步明确梓醇作用机制，通过离体卵巢颗粒细胞模型明确ERK、p38MAPK、JNK信号通路参与了损伤作用，梓醇可通过影响MAPK 通路中c-fos上下游12个差异基因，上调c-fos蛋白水平的表达，其中从而抑制卵巢颗粒细胞这种磷酸化，发挥卵巢保护作用。明确卵巢颗粒细胞功能状态变化调控机制及梓醇作用机制，将为以后阐明在卵巢功能衰退发病机制及梓醇治疗卵巢衰老系统疾病提供理论基础。