糖尿病肾病肾间质纤维化“肾络癥瘕聚散消长”病机内涵

糖尿病肾病肾间质纤维化的主要病理特点为胞外基质降解异常,在肾小球系膜和肾小管间质进行性沉积,这与其"肾络癥瘕聚散消长"的核心病机存在相似之处。转化生长因子(transforming growth factor-bata, TGF-β)/Smad作为致肾间质纤维化的重要通路之一,其平衡失调受UPS和自噬的双重影响,这与中医"肾络癥瘕聚散消长"理论中,"邪聚正散"的失衡状态相一致。前期已证实,和解聚散法可以抑制TGF-β/Smad通路缓解糖尿病肾病肾间质纤维化,其作用机制可能与调节糖尿病肾病病状态下自噬与泛素蛋白降解途径的平衡有关,但仍需加强实验验证明确和解聚散法干预TGF-β/Smad信号通路是否与抑制泛素蛋白酶体降解通路有关,是否与激活自噬有关,进一步研究和解聚散法干预自噬-溶酶体降解途径的具体节点,同时加强体外实验,阐明其含药血清是否通过干预上述通路发挥作用,明确干预上述通路可增加TGF-β/Smad通路中哪些关键蛋白的降解。今后需进一步研究和解聚散法调节糖尿病肾病病状态下自噬与泛素蛋白降解途径的具体节点,明确和解聚散法的配伍、用量,明确TGF-β的平衡调节,有效延缓糖尿病肾病肾间质纤维化,进一步发展"肾络癥瘕聚散消长"病机理论。

Pathogenesis of "Ebb and Flow of Renal Collateral Gatherings" in Renal Interstitial Fibrosis of Diabetic Nephropathy from Perspective of Abnormalities Autophagy and Ubiquitin-Proteasome System

Abnormal degradation of extracellular matrix and progressive deposition in the mesangium and tubule interstitium is the main pathological features of DKD renal interstitial fibrosis, which is similar to the core pathogenesis of "ebb and flow of renal collateral gatherings".As one of the important renal interstitial fibrosis pathways, TGF-β/Smad is affected by both autophagy and the ubiquitin-proteasome system.The unbalanced regulation of this pathway is consistent with the imbalance of "Xie Ju Zheng San"( "ebb and flow of Zheng Qi and Evil factors") in the theory of "Ebb and Flow of Renal Collateral gatherings".It has been proved that and He Jie Ju San Method can inhibit the TGF-β/Smad pathway to alleviate DKD renal interstitial fibrosis, and its mechanism may be related to regulating the balance of autophagy and ubiquitin-protein degradation pathway in DKD disease.However, it is still necessary to strengthen experiments to verify whether the He Jie Ju San Method interferes with TGF-β/Smad signaling pathway is related to the inhibition of the ubiquitin-proteasome degradation pathway and to the activation of autophagy.Further study the specific nodes of the He Jie Ju San Method that interferes with the autophagy-lysosomal degradation pathway, and at the same time strengthen in vitro experiments to clarify whether its medicated serum plays a role by intervening in the above pathways, and which key proteins in the TGF-β/Smad pathway can be degraded can be increased by intervening in the above pathways.In the future, it is necessary to further study the specific nodes of autophagy and ubiquitin protein degradation pathways under the condition of diabetic nephropathy by He Jie Ju San Method, clarify the compatibility and dosage of the method with disaggregation method, and clarify the balance regulation of TGF-β,and effectively delay the renal interstitial fibrosis of diabetic nephropathy, and further develop the pathogenesis theory of "miniature mass of renal collateral gathering, dissipating, growing, and decreasing".