临床与实验病理学杂志2024，Vol.40Issue(5)：509-514,6.DOI:10.13315/j.cnki.cjcep.2024.05.012
A-485 通过抑制 P300/CBP 诱导的 H3K18ac/H3K27ac减轻糖尿病肾小管细胞脂质沉积
A-485 alleviates tubular lipid accumulation by inhibiting H3K18ac/H3K27ac induced by P300/CBP in diabetic mice
摘要
Abstract
Purpose To investigate the protective effect and mechanism of A-485 on renal tubular injury in diabetic mice.Methods Eighteen male C57BL/6J mice were randomly divided into three groups:Control group,diabetic kidney dis-ease(DKD)group and A-485 treatment group.The DKD mice model was established by feeding high-fat diet for 8 weeks and intraperitoneal injection of streptozotocin for 5 days.Subsequent-ly,the A-485 treatment group was given A-485(10 mg/kg/day)by intraperitoneal injection every other day for 4 weeks.After treatment,the renal function,P300 enzyme activity and lipid deposition in renal tissue were measured.Western blot a-nalysis was performed to detect SREBP-1,FASN,ACC,ChREBP,P300,CBP,H3K18ac and H3K27ac protein levels.Results Compared with control mice,the levels of FBG,BUN,Scr and UAE were significantly increased in diabetic mice(FBG:2.52 times,BUN:2.89 times,Scr:2.13 times,UAE:4.21 times),while diabetic mice treatment with A-485 exhibi-ted a remarkable decrease on BUN,Scr and UAE(BUN:0.511 times,Scr:0.636 times,UAE:0.574 times,P＜0.01).The results of the transmission electron microscopy and oil red O stai-ning showed that A-485 treatment prevents lipid droplets forma-tion and up-regulation of SREBP-1,FASN,ACC and ChREBP in renal tubular cells of diabetic mice(SREBP-1:0.544 times,FASN:0.449 times,ACC:0.306 times,ChREBP:0.317 times,P＜0.01).Furthermore,A-485 intervention downregu-lated the enzyme activity of P300(0.546 times)and suppressed the expression of H3K18ac(0.337 times)and H3K27ac(0.308 times,P＜0.01).Conclusion A-485 can significant-ly improve renal lipid metabolic disorder in diabetic mice,which may be achieved by inhibiting p300-induced H3K18ac and H3K27ac.关键词
糖尿病肾病/P300/CBP/A-485/脂质沉积/乙酰化Key words
diabetic kidney disease/P300/CBP/A-485/lipid accumulation/acetylation分类
医药卫生引用本文复制引用
孟丽,朱艳,杨琰,吴婷,任韫卓,杜林珊,曾士洁,杜春阳..A-485 通过抑制 P300/CBP 诱导的 H3K18ac/H3K27ac减轻糖尿病肾小管细胞脂质沉积[J].临床与实验病理学杂志,2024,40(5):509-514,6.基金项目
国家自然科学基金青年基金(82000773)、河北省高等学校科学技术研究项目青年基金(QN2021104)、河北省自然科学基金(H2022206463) （82000773）
