肾炎防衰液通过调节自噬与泛素蛋白酶体降解途径抑制糖尿病肾脏病TGF-β/Smad通路失衡的作用机制研究

在前期研究中我们发现肾炎防衰液治疗糖尿病肾脏病（DKD）与抑制TGF-β/Smad通路有关，因此提出假说：其对抗TGF-β/Smad通路失衡与机体两条调控蛋白降解的重要途径有关，其通过激活自噬及阻断泛素蛋白酶体降解通路分别增加了TGF-β/Smad通路中正及负性调控蛋白的降解。本研究首先探讨DKD患者肾脏细胞TGF-β/Smad及两条降解通路中各关键蛋白表达的相互关系；然后借DKD动物模型，探讨肾炎防衰液抑制TGF-β/Smad通路是否与激活自噬或抑制泛素蛋白酶体通路进而增加或减少相关蛋白降解有关，与干预哪些节点有关；最后借DKD致病因素诱导的肾脏细胞模型，以基因干预或化学试剂阻断上述降解通路，探讨肾炎防衰液含药血清是否通过干预上述两条通路发挥作用，并进一步研究其干预TGF-β/Smad通路中哪些关键蛋白的降解，并最终有望基于中医阴阳平衡理论阐明“肾络癥瘕”理论的科学内涵。

Our previous research had confirmed Shenyanfangshuai fluid’s efficacy in diabetic kidney disease (DKD) by inhibiting TGF-β/Smad pathway. So we put forward a hypothesis that its inhibiting effect on TGF-β/Smad pathway may be associated with two protein degradation pathways by activating autophagy and inhibiting ubiquitin-proteasome pathway. In this study we first investigate the relationship between the key proteins of TGF-β/Smad pathway and the two protein-degradation pathways in DKD patients. Then we investigate whether Shenyanfangshuai fluid’s efficacy was associated with activating autophagy and inhibiting ubiquitin proteasome pathway in rat models. And at last further investigate whether Shenyanfangshuai fluid’s efficacy was associated with the two pathways and find the specific protein of TGF-β/Smad pathway they act on via genetic interference or chemical interference in cell models. and finally it is expected to elucidate the meaning of Shenluozhengjia theory on the basic of TCM yin and yang theory .