title: Mechanistic study of endogenous skin lesions in diabetic rats.
abstract: Pathological and physiological changes in dermal tissue in a rat model of diabetes mellitus (DM) were investigated. Sixteen male 8-week-old Sprague-Dawley rats were randomized into two groups of eight, the DM group (Group DM) and the normal control group (Group (NC) normal control). Group DM rats were injected with streptozotocin (STZ) intraperitoneally at a dose of 65 mg/kg body weight. Group NC rats were injected with the same volume of citric acid buffer. All rats were sacrificed 12 weeks later. The impact of exposure to (AGE) advanced glycation end products-modified human serum albumin (AGE-HSA) on epidermal cells and ECV304 cells was evaluated in cell culture experiments. The diabetic rats exhibited changes in skin tissue, including a decrease in thickness, disappearance of the multilayer epithelium structure, degeneration of collagen fibres and an increase in the infiltration of inflammatory cells, in addition to a significant increase in skin glucose and AGEs. Moreover, diabetic rats had increased plasma glycosylated protein (GSP) and malondialdehyde (MDA) and decreased plasma glutathione (GSH). The percentage of epidermal cells in S phase was similar between the two group rats; however, there was a marked decrease in the G2/M phase in Group DM. Additionally, exposure of ECV304 cells to AGE-HSA led to a time-dependent and dose-dependent increase in apoptosis. Therefore, the high glucose in the skin tissue, coupled with the accumulation of toxic substances such as AGEs, promote the dysfunction of dermal cells and/or the matrix. This may be a significant mechanism of diabetes-induced early-stage endogenous skin damage.
authors.affiliation: Department of Endocrinology, Chang Zheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiang-fang
authors.initials: XF
authors.lastname: Chen
authors.forename: Wei-dong
authors.initials: WD
authors.lastname: Lin
authors.forename: Shu-liang
authors.initials: SL
authors.lastname: Lu
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.forename: Kui
authors.initials: K
authors.lastname: Ge
authors.forename: Yong-quan
authors.initials: YQ
authors.lastname: Shi
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Zou
authors.forename: Zhi-min
authors.initials: ZM
authors.lastname: Liu
authors.forename: Wan-qing
authors.initials: WQ
authors.lastname: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D004817:Epidermis / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D017127:Glycation End Products, Advanced / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D055806:Microvessels / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology; D000075462:Serum Albumin, Human; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D012871:Skin Diseases / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D017127:Glycation End Products, Advanced; D012709:Serum Albumin; C109748:advanced glycation end products-human serum albumin; D008315:Malondialdehyde; D005978:Glutathione; D005947:Glucose; D000075462:Serum Albumin, Human