ABSTRACT
Diabetic nephropathy （DN） is among the common microvascular complications of diabetes. In recent years， the incidence has been on the rise with the increase in prevalence of diabetes， threatening the health of human. The early stage of DN is characterized by excessive accumulation of extracellular matrix （ECM） and thickening of glomerular basement membrane which result in glomerular mesangial proliferation and massive collagen deposition. The late stage features glomerular sclerosis and renal fibrosis （RF）. It has been confirmed that RF is the key pathological process for the development of DN. Therefore， it is the research focus to explore the pathogenesis and treatment methods of RF. It has been frequently verified that Chinese medicine is superior in the treatment of diabetic RF. It relieves diabetic RF by regulating transforming growth factor-β （TGF-β）， secretory glycoprotein （Wnt）/β-catenin， nuclear factor-κB （NF-κB）， Notch， mitogen-activated protein kinase （MAPK）， and other signaling pathways. Therefore， this paper reviews the pathogenesis of diabetic RF and the treatment with Chinese medicine， which is expected to serve as a reference for clinical application of Chinese medicine in the treatment of diabetic RF.
ABSTRACT
Objective:From a new perspective，to explore therapeutic effect of Huidouba (HDB) on alleviating kidney oxidative damage in rats with diabetic nephropathy (DN) and provide a scientific basis for developing HDB as a potential Tibetan medicine for treatment of DN. Method:Rats were fed with high-fat diet (HFD) and injected with streptozocin (STZ, 65 mg·kg-1) intraperitoneally to induce DN model, while rats in Blank group were injected with an equal volume of vehicle and fed with normal chow. The successfully modeling DN rats were randomly divided into three groups, 8 rats per group, DN model group (10 mL·kg-1·d-1), Metformin group (0.045 g·kg-1·d-1) and HDB group (0.18 g·kg-1·d-1). Monitor body weight (BW) and fasting blood glucose (FBG) weekly, and collect 24 hours urine before and after medication to examine microalbuminuria (mAlb). Calculate kidney index (KI) after sacrificing, analyze mAlb, serum creatinine (SCr) and blood urea nitrogen (BUN) with a fully automatic biochemical analyzer. Histopathology of kidney was observed by Masson staining. Lipid peroxidation malondialdehyde (MDA) assay kit was used to examine MDA content in kidney tissue. Nox4, as a subtype of triphosphopyridine nucleotide (NADPH) oxidase family was determined by Western blot and immunofluorescence assay of kidney tissue. Result:Compared with blank group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in DN model group were increased (P<0.01), tissue damage was obvious and Nox4 expression in glumeruli was increased significantly (P<0.01). Compared with DN model group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in drug administration groups were decreased (P<0.01), kidney injury was alleviated and Nox4 expression was down-regulated（P<0.01）. Conclusion:HDB as a Yiqiyangyin Tibetan medicine, could ease oxidative stress injury of kidney and reduce proteinuria in DN rats, thus prevent the development of DN. Its mechanism is closely related to down-regulating Nox4 expression of kidney tissue in DN rats.