糖尿病肾脏病“内热致癥”病机内涵

Pathogenesis and Connotation of"Internal Heat Induced Lump Syndrome"of Diabetic Kidney Disease

线粒体功能障碍是糖尿病肾脏病(diabetic kidney disease,DKD)的重要发病机制。持续高血糖状态可能通过抑制AMPK-ULK1通路,抑制线粒体自噬,导致受损线粒体未能被及时清除,线粒体功能受损,从而加快DKD的进展。另外,基于“内热致癥”理论,DKD基本病机为伤阴耗气,痰郁热瘀互相胶结于络脉,形成微型癥瘕,“内热”是肾络癥瘕形成的初始病机,并贯穿于病程始终。随着DKD进程内热证表现形式不同,兼夹证候亦不同:早期内热主要表现为燥热、郁热,常并见阴虚证、气虚证;中期主要表现为结热、湿热,常并见气虚证,逐渐形成肾络微型癥瘕;晚期主要为浊热、湿热,阳虚证比例升高,浊毒内生。中医药对延缓DKD的进展有明确效果,清热消癥法可减轻机体蛋白尿、改善自噬受阻状态。探讨清热消癥法能否通过调控能量代谢的关键传感器——AMPK-ULK1通路,激活线粒体自噬,清除损伤的线粒体,改善线粒体功能,减轻肾小球硬化,延缓DKD发展。

Mitochondrial dysfunction is one of the important pathogenesis of diabetic kidney disease(DKD).Sustained hyperglycemia may inhibit mitochondrial autophagy by inhibiting AMPK-ULK1 pathway,leading to the failure of timely clearance of damaged mitochondria,impaired mitochondrial function,and accelerating the progression of DKD.In addition,based on the theory of"internal Heat induced lump",the basic etiology of DKD was damage to Yin and loss of Qi,as well as the mixed Phlegm,Heat and depression and stasis forming lump in collateral."Internal Heat"is the initial etiology of lump of renal collateral and could be seen throughout the course of the disease.With the different manifestations of Heat syndrome in the process of DKD,the concurrent syndrome is also different:in the early stage,the main manifestations of internal Heat are desiccated Heat,stagnation Heat as well as Yin deficiency syndrome and Qi deficiency syndrome are often seen.In the middle stage,the manifestations are mainly Heat and Dampness,often accompanied by Qi deficiency syndrome,and gradually miniature lump of kidney collateral get formed.In the late stage,there were mainly turbid Heat and Damp-Heat,the proportion of Yang deficiency syndrome increased and turbid toxicity is produced.Traditional Chinese medicine has a definite effect on delaying the progression of DKD.With clearing Heat and eliminating lump method,the proteinuri can be reduced the impaired autophagy can be recovered.It is of theoretical and scientific significance to explore whether clearing Heat and eliminating disease can activate mitochondrial autophagy,remove damaged mitochondria,improve mitochondrial function,reduce glomerular sclerosis and delay the development of DKD through AMPK-ULK1 pathway,a key sensor of regulating energy metabolism.