目的 探讨低聚原花青素(oligoprocyanidins, OPC)对糖尿病肾病(diabetic kidney disease,DKD)大鼠足细胞上皮-间质转化(Epithelial-to-Mesenchymal transition, EMT)的影响。方法 选择雄性SD大鼠20只,用链脲佐菌素、高脂高糖饮食制造DKD模型。成模后随机分为模型组和OPC组(常规饲养基础上加喂OPC),另取10只雄性SD大鼠作为对照组。8周后比较各组大鼠的肾功能及组织形态学变化。Western blot分析EMT相关蛋白的水平。结果 OPC能明显降低糖尿病肾病大鼠血糖、血肌酐、尿素氮和尿蛋白水平(P<0.05),减轻DKD大鼠的肾组织形态学改变。电镜下OPC组大鼠足细胞部分融合,出现自噬泡。OPC上调DKD大鼠足细胞的E-cadherin蛋白的表达,下调Vimentin、Twist1蛋白的表达。结论 OPC可诱导DKD大鼠足细胞自噬,减轻足细胞EMT,为DKD的进一步研究提供了基础。
Abstract
Objective To investigate the effect of oligoprocyanidins(OPC) on epithelial-to-mesenchymal transition (EMT) of podocytes in rats with diabetic kidney disease (DKD). Methods Thirty male SD rats were randomly divided into the control group, model group and OPC group [500 mg/(kg·d), 8 weeks]. The renal function of different groups was compared. The histological changes were observed via light and electron microscopy. The levels of EMT-related proteins were analyzed by Western blot. Results OPC could significantly reduce the levels of blood glucose, serum creatinine, urea nitrogen and urinary protein in DKD rats (P<0.05). Under an electron microscope, podocytes in the OPC group partially fused and autophagic vesicles appeared. OPC up-regulated the expression of E-cadherin but down-regulated the expression of vimentin and Twist1 in podocytes of DKD rats. Conclusions OPC can induce podocyte autophagy and reduce podocyte EMT in DKD rats.
关键词
肾小球足细胞 /
上皮-间质转化 /
原花青素 /
自噬
Key words
glomerular podocytes /
epithelial-to-mesenchymal transition /
oligoprocyanidins /
autophagy
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参考文献
[1] 郑 文, 潘少康, 刘东伟,等. 糖尿病肾病治疗进展[J]. 中华肾脏病杂志, 2020, 36(6):476-480.
[2] Marikanty R K, Gupta M K, Cherukuvada S V, et al. Identification of urinary proteins potentially associated with diabetic kidney disease[J].Indian J Nephrol, 2016, 26(6):434-445.
[3] Podgórski P, Konieczny A, Lis L, et al. Glomerular podocytes in diabetic renal disease[J].Adv Clin Exp Med, 2019,28(12):1711-1715.
[4] Han Q, Zhu H, Chen X, et al. Non-genetic mechanisms of diabetic nephropathy[J].Front Med, 2017,11(3):319-332.
[5] 郑铁骑, 邢翔飞. EMT促肾间质纤维化机制及干预药物[J]. 广东医学, 2017, 13(38):146-148.
[6] 王 颖, 张桂芳, 赵 亮,等. 葡萄籽提取物原花青素对糖尿病小鼠的抗氧化作用[J]. 中国老年学杂志, 2014, 34(2):433-435.
[7] 韦金英, 史永红, 任韫卓,等. 葡萄籽原花青素对糖尿病db/db小鼠肾组织细胞表型转化的影响[J]. 临床与实验病理学杂志, 2017,33(8):858-862.
[8] 吕晓楠, 董 铮, 李春进,等. 低聚原花青素对葡聚糖硫酸钠诱导小鼠溃疡性结肠炎的保护作用[J]. 武警医学, 2020, 31(7): 572-575.
[9] 翁晓璐, 林孙东, 倪永青,等. 成纤维细胞生长因子-21通过抑制EMT改善糖尿病肾纤维化[J]. 医学研究杂志, 2019, 48(6):35-41.
[10] 吴 静, 高永棣, 俞佳丽,等. HMGN1在糖尿病肾病小鼠肾小管上皮-间质转化中的作用[J]. 中华内分泌代谢杂志, 2019, 35(8):697-702.
[11] Srivastava S P, Koya D, Kanasaki K. MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT[J]. Biomed Res Int, 2013, 13:125469.
[12] 胡琼英, 艾承锦, 陈高莉,等. 内皮细胞成纤维生长因子受体1缺陷所致EndMT调控TGFβ信号通路诱导上皮细胞EMT[J]. 中华内分泌代谢杂志, 2019, 35(11):969-972.
[13] 王卫娜. 葡萄籽原花青素对糖尿病大鼠肾脏GLUT2及肾功能的影响[J]. 中医临床研究, 2016, 8(11):10-12.
[14] Gonzalez-Abuin N, Pinent M, Casanova M A, et al. Procyanidins and their healthy protective effects against type 2 diabetes[J].Curr Med Chem, 2015,22(1):39-50.
[15] 张尚维,李明星,赵 蕊,等. 糖尿病肾病发生的氧化应激机制及抗氧化治疗的研究进展[J]. 中国药理学与毒理学杂志, 2020, 34(8):76-82.
[16] 邱 腾, 王 迪. 葡萄籽原花青素对糖尿病大鼠肾缺血再灌注损伤的影响[J]. 中国临床药理学杂志, 2020,36(14):2036-2038.
[17] Stohs S J, Ray S. Anti-diabetic and anti-hyperlipidemic effects and safety of salaciareticulata and related species[J].Phytother Res, 2015, 29(7):986-995.
[18] Yang D, Livingston M J, Liu Z,et al. Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential[J].Cell Mol Life Sci,2018,75(4):669-688.
[19] 刘尚军, 彭 兴, 周志宏. 葡萄籽原花青素对自发性高血压大鼠肾纤维化的改善及肾损伤保护作用[J]. 实用医学杂志, 2019,35(17):2683-2687.
[20] 王阜蕾, 张妍春, 陈媛媛,等. STZ诱导的糖尿病模型小鼠肾脏的上皮-间质转分化研究[J]. 现代生物医学进展, 2017, 17(18):3413-3418.
[21] Sun L, Chen Z, Liu X, et al. Curcumin ameliorates epithelial-to-mesenchymal transition of podocytes in vivo and in vitro via regulating caveolin-1[J]. Biomed Pharm, 2014, 68(8):1079-1088.
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