[1]张世鲁,张 丽,温文杰,等.全反式维甲酸对糖尿病肾病模型大鼠转化生长因子β1基因甲基化水平影响的实验研究[J].陕西医学杂志,2023,52(7):788-792.[doi:DOI:10.3969/j.issn.1000-7377.2023.07.003]
 ZHANG Shilu,ZHANG Li,WEN Wenjie,et al.Effects of all-trans retinoic acid on methylation level of TGF-β1 gene in diabetic nephropathy rat models[J].,2023,52(7):788-792.[doi:DOI:10.3969/j.issn.1000-7377.2023.07.003]
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全反式维甲酸对糖尿病肾病模型大鼠转化生长因子β1基因甲基化水平影响的实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年7期
页码:
788-792
栏目:
基础研究
出版日期:
2023-07-05

文章信息/Info

Title:
Effects of all-trans retinoic acid on methylation level of TGF-β1 gene in diabetic nephropathy rat models
作者:
张世鲁12 张 丽12温文杰3张启伦3武晓影3薛竞帆3 周 婉3 叶山东13
(1.中国科学技术大学附属第一医院内分泌科糖尿病实验室,安徽 合肥 230001; 2.皖南医学院研究生学院,安徽 芜湖 241002; 3.中国科技大学生命科学与医学部,安徽 合肥 230001)
Author(s):
ZHANG ShiluZHANG LiWEN WenjieZHANG QilunWU XiaoyingXUE JingfanZHOU WanYE Shandong
(Diabetes Laboratory,Department of Endocrinology,First Affiliated Hospital of University of Science and Technology of China,Hefei 230001,China)
关键词:
全反式维甲酸 糖尿病肾病 肾脏纤维化 转化生长因子β1 甲基化
Keywords:
All-trans retinoic acid Diabetic nephropathy Renal fibrosis TGF-β1 Methylation
分类号:
R 587.2
DOI:
DOI:10.3969/j.issn.1000-7377.2023.07.003
文献标志码:
A
摘要:
目的:探讨全反式维甲酸(ATRA)对糖尿病肾病(DN)模型转化生长因子β1(TGF-β1)基因甲基化水平的影响。方法:将30只成年雄性SD大鼠随机分为对照组、DN组、DN+ATRA组,每组10只。采用高糖高脂饮食加腹腔注射小剂量链脲佐菌素建立DN大鼠模型,对照组和DN组给予等体积0.9%氯化钠溶液灌胃,DN+ATRA组给予5 mg/kg ATRA灌胃,连续干预4周。观察各组大鼠24 h尿蛋白和血液生化指标,肾脏组织行HE染色和PAS染色,选择MS-PCR检测各组大鼠肾脏中TGF-β1基因的DNA甲基化水平,选择逆转录聚合酶链式反应(RT-PCR)、Western blot法及免疫组织化学检测肾脏组织TGF-β1 mRNA及蛋白表达。结果:与对照组比较,DN组大鼠空腹血糖(FBG)、血肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白升高(均P<0.05)。与DN组比较,DN+ATRA组大鼠FBG、BUN、Scr、24 h尿蛋白降低,但高于对照组(均P<0.05)。HE染色和PAS染色DN组肾小球形状不规则,系膜基质增多着玫瑰红色,部分肾小管有萎缩且存在管腔扩张,肾小管周围有较多炎症细胞浸润和组织增生,DN+ATRA组大鼠肾脏组织病变情况明显减轻。DN组大鼠肾脏组织TGF-β1基因的DNA甲基化水平相较于对照组显著降低,DN+ATRA组大鼠肾脏组织TGF-β1基因的DNA甲基化水平相较于DN组显著升高(P<0.05)。对照组大鼠肾脏组织TGF-β1mRNA及蛋白水平显著低于DN组,DN+ATRA组大鼠肾脏组织TGF-β1mRNA和蛋白水平显著高于对照组,低于DN组(均P<0.05)。结论:ATRA能通过升高TGF-β1基因的DNA甲基化水平,抑制DN大鼠肾脏组织TGF-β1mRNA和蛋白表达,改善DN大鼠肾脏组织的纤维化程度。
Abstract:
Objective:To investigate the effects of all-trans retinoic acid(ATRA)on the methylation level of transforming growth factor β1(TGF-β1)gene in diabetic nephropathy(DN)model.Methods:Thirty adult male SD rats were randomly divided into control group,DN group,DN+ATRA group,with 10 rats in each group.A rat model of DN was established by high-sugar and high-fat diet plus intraperitoneal injection of low-dose streptozotocin.The normal group and DN group were given gavage with the same volume of 0.9% sodium chloride solution,and 5 mg/kg ATRA was given for gastric gavage in the DN+ATRA group for 4 weeks.The 24-hour urine protein and blood biochemical indexes of rats in each group were observed.HE staining and PAS staining were performed for kidney tissue.The methylation level of TGF-β1 gene in the kidneys of each group was detected by MS-PCR.RT-PCR,Western blot and immunohistochemistry were used to detect the expressions of TGF-β1 mRNA and protein in renal tissue.Results:Compared with control group,the levels of FBG,Scr,BUN and 24-hour urine protein were increased in DN group(all P<0.05).Compared with DN group,the levels of FBG,BUN,Scr and 24-hour urine protein were decreased in DN+ATRA group,but higher than those in control group(all P<0.05).HE staining and PAS staining showed that the glomerular shape was irregular,the mesangial matrix was increased and the rose-red color appeared,some renal tubules were atrophic and luminal dilatation existed,and there were more inflammatory cell infiltration and tissue proliferation around the renal tubules in DN group; the pathological changes of renal tissue in DN+ATRA group were significantly alleviated.The DNA methylation level of TGF-β1 gene in renal tissue of rats in DN group was significantly lower than that in the control group,and the DNA methylation level of TGF-β1 gene in renal tissue of rats in DN+ATRA group was significantly higher than that in DN group(all P<0.05).The levels of TGF-β1 mRNA and protein in control group were significantly lower than those in DN group,and those in the DN+ATRA group were significantly higher than those in control group and lower than those in DN group(all P<0.05).Conclusion:ATRA can inhibit the expressions of TGF-β1 mRNA and protein in the kidney of DN rats by increasing the level of DNA methylation of TGF-β1 gene,and improve the degree of fibrosis in the kidney of DN rats.

参考文献/References:

[1] 闫 妮,刘玲娇,余湘尤,等.中性粒细胞与淋巴细胞比值在2型糖尿病合并糖尿病肾病患者中的变化及检测价值研究[J].陕西医学杂志,2021,50(6):673-677.
[2] 方锦颖,王一冲,神原优滋,等.基于网络药理学和分子对接探究肾康注射液治疗糖尿病肾病作用机制[J].陕西中医,2021,42(12):1798-1802.
[3] 蒋俊兰,刘尚全.血尿酸/肌酐比值与早期糖尿病肾脏病进展的关系[J].国际内分泌代谢杂志,2022,42(1):17-20,31.
[4] 沈金峰,胡良伟,胡 芳,等.加味参芪地黄汤对糖尿病肾病TGF-β1、VEGF的影响[J].辽宁中医杂志,2021,48(7):91-95.
[5] Rafiee Z,Orazizadeh M,Nejad-Dehbashi F,et al.Mesenchymal stem cells derived from the kidneycan ameliorate diabetic nephropathy through the TGF-β/Smad signaling pathway[J].Environ Sci Pollut Res Int,2022,29(35):53212-53224.
[6] 李正东,方 凡,徐 波,等.全反式维甲酸对抗肾小球基底膜肾炎小鼠模型肾脏损害的保护作用[J].中华肾病研究电子杂志,2019,8(3):114-120.
[7] 张 倩,杨丽铃,吴 琼,等.糖尿病肾病患者TGF-β1基因表达调控区甲基化水平变化[J].中华肾脏病杂志,2016,32(2):99-105.
[8] Rafiee Z,Orazizadeh M,Nejad-Dehbashi F,et al.Mesenchymal stem cells derived from the kidney can ameliorate diabetic nephropathy through the TGF-β/Smad signaling pathway[J].Environ Sci Pollut Res Int,2022,29(35):53212-53224.
[9] Siriwattanasit N,Satirapoj B,Supasyndh O.Effect of oral carnosine supplementation on urinary TGF-β in diabetic nephropathy:A randomized controlled trial[J].BMC Nephrol,2021,22(1):236.
[10] 陈 旭,吴建华,郭乃凤,等.全反式维甲酸对环孢素诱导的肾小球系膜细胞增殖与凋亡的影响及其机制[J].器官移植,2017,8(6):465-471.
[11] 张 磊,陈秀萍,蒋 玲,等.全反式维甲酸对肾小球硬化大鼠肾小球TRPC6表达的影响[J].实用医学杂志,2016,32(23):3827-3831.
[12] 陈艳霞,房向东,黄 翀,等.全反式维甲酸对高糖诱导肾小管上皮细胞增殖及凋亡的影响[J].天津医药,2016,44(1):50-52.
[13] 李红艳,苏彩虹,李静纯,等.全反式维甲酸对大鼠缺血再灌注肾损伤的保护作用[J].中国医师杂志,2018,20(9):1316-1319.
[14] 周添标,钟红珍,钟志青,等.全反式维甲酸对大鼠肾间质纤维化的延缓作用及其可能分子机制[J].广西医学,2020,42(7):830-834.
[15] 陆晓涵,吕富刚,孔凡武.DNA甲基化调节糖尿病肾脏病肾脏纤维化的研究进展[J].国际遗传学杂志,2022,45(3):214-219.
[16] Hassan HM,Mahran YF,Ghanim A.Ganoderma lucidum ameliorates the diabetic nephropathy via down-regulatory effect on TGF-β1 and TLR-4/NF-κB signalling pathways[J].J Pharm Pharmacol,2021,73(9):1250-1261.
[17] Habib HA,Heeba GH,Khalifa M.Comparative effects of incretin-based therapy on early-onset diabetic nephropathy in rats:Role of TNF-α,TGF-β and c-caspase-3[J].Life Sci,2021,278(2):119624.
[18] Mohammed ME,Abbas AM,Badi RM,et al.Effect of Acacia senegal on TGF-β1 and vascular mediators in a rat model of diabetic nephropathy[J].Arch Physiol Biochem,2020,128(6):1548-1558.
[19] 李国宏,纪品川,王雅君.黄芪桂枝五物汤对老年糖尿病肾病转化生长因子-β基因表达调控区甲基化的影响[J].世界中医药,2018,13(3):644-647.
[20] 许召君,陈小彬,才保加,等.全反式维甲酸与肝脏疾病的关系及其分子机制研究进展[J].中国普通外科杂志,2021,30(7):859-865.
[21] 陈 珂,许君望,周 琦,等.全反式维甲酸对TGF-β1刺激的肝星状细胞COL1α2、MMP-2、TIMP-1以及信号通路的影响[J].西安交通大学学报,2017,38(6):857-861.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81800713); 安徽省中央引导地方科技发展专项课题(2017070802D147)
更新日期/Last Update: 2023-07-05