实用医学杂志 ›› 2020, Vol. 36 ›› Issue (23): 3194-3198.doi: 10.3969/j.issn.1006⁃5725.2020.23.006

• 基础研究 • 上一篇    下一篇

组蛋白甲基化转移酶2在糖尿病肾病小鼠肾组织中的表达变化及其意义

简久莹,张妮, 余婷,王笑笑,伍聪聪,徐卫卫, 郭兵,刘丽荣   

  1. 1贵州医科大学附属医院临床检验中心(贵阳550004);2 贵州医科大学医学检验学院临床血液学教研室(贵阳550004);3 贵阳市第一人民医院输血科(贵阳550002);4贵州医科大学贵州省常见慢性疾病发病机制及药物研究重点实验室(贵阳550025)

  • 出版日期:2020-12-10 发布日期:2020-12-23
  • 通讯作者: 刘丽荣E⁃mail:liliya8656@sina.com

Expression and significance of histone methyltransferase SMYD2 in renal tissue of diabetic nephropathy mice and its expression in renal tissue of diabetic nephropathy mice

JIAN Jiuying,ZHANG Ni,YU Ting,WANG Xiaoxiao,WU Congcong,XU Weiwei ,GUO Bing,LIU Lirong.#br#   

  1. Department of Clinical Hematology,Guizhou Medical University,Guiyang 550004,China;*Clinical Laboratory Center,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China

  • Online:2020-12-10 Published:2020-12-23
  • Contact: LIU Lirong E⁃mail:liliya8568@sina.com
  • Supported by:
    国家自然科学基金资助项目(编号:81860134);贵州省高层次留学人才创新创业择优资助项目(编号:留学人才择优资助合同(2018)01号)

摘要:

目的 检测组蛋白甲基化转移酶2(SET and MYND domain containing 2,SMYD2)在糖尿病小鼠肾组织中的表达变化,分析其与上皮细胞⁃间充质细胞转化(epithelial⁃mesenchymal transformation,EMT)的相关性,为临床上治疗糖尿病肾病(diabetic nephropathy,DN)提供新的方向。方法 24 只雄性C57BL/6小鼠随机分为正常对照(NC)组、DM12周组、DM24周组和DM28周组,每组6只。采用腹腔注射链脲佐菌素(streptozotocin,STZ)复制DM小鼠模型,处死小鼠后收集血清和肾组织,全自动生化分析仪测血糖(BG)、血肌酐(Scr)和尿素氮(BUN);利用HE 和Masson 染色进行肾脏病理分析;应用Western blot 方法检测α⁃平滑肌肌动蛋白(α⁃MA)、波形蛋白(Vimentin)、SMYD2、转化生长因子⁃β1(TGF⁃β1)和E⁃钙黏素(E⁃cadherin)的表达。结果 与NC组相比,DM组小鼠BG、Scr和BUN水平均明显增加(P < 0.05),24周组和28周组肾组织出现明显的病理改变和纤维增生,α⁃MA、Vimentin、SMYD2 和TGF⁃β1 蛋白表达增加(P < 0.05),E⁃cadherin蛋白表达减少(P < 0.05),其中SMYD2与E⁃cadherin的表达呈负相关,与α⁃MA,Vimentin和TGF⁃β1的表达呈正相关。结论 SMYD2在DM小鼠肾组织中表达上调,推测其可能和TGF⁃β1表达上调共同参与EMT的发生,进而参与调控DN的发生发展。

关键词: 组蛋白甲基化转移酶2, 糖尿病肾病, 上皮细胞?间充质细胞转化, 转化生长因子?β1

Abstract: Objective To detect the expression of SET and MYND domain containing 2(SMYD2)inrenal tissue of diabetic mice and analyze its correlation with epithelial⁃ mesenchymal transition(EMT),whichprovides a new direction for the clinical treatment of diabetic nephropathy. Methods Twenty⁃four male C57BL/6mice were randomly assigned to normal control(NC)group,DM12 week group,DM24 week group and DM28week group,6 mice in each group,were intraperitoneal injected with Streptozotocin⁃induced replication of DMmouse model. Mice were sacrificed at the corresponding time. Serum and renal tissue samples were collected.Blood glucose,serum creatinine and blood urea nitrogen were measured by biochemical methods. Pathologicalchanges of renal tissue were observed after HE and Masson staining. The expression of ⁃SMA,Vimentin,SMYD2,TGF⁃β1 and E⁃adherin were detected by Western blot. Results Compared with NC group,blood glucose,serumcreatinine and blood urea nitrogen of the diabetic group increased(< 0.05). Significant pathological changesand fibrous hyperplasia were observed in renal tissues at 24 weeks and 28 weeks. α⁃MA,Vimentin,SMYD2and TGF⁃β1 protein expression wassignificantly increased(< 0.05)at 24 weeks and 28 weeks,E⁃cadherin wasdecreased(< 0.05). The results of correlation analysis showed that SMYD2 was negatively correlated withE⁃cadherin expression and positively correlated with α ⁃MA,Vimentin and TGF⁃ β1 expression. Conclusion SMYD2 expression is upregulated in renal tissue of DM mice,and it is speculated that SMYD2 may participate in the occurrence of EMT together with the up⁃regulation of TGF⁃β1 expression,and thus participate in the regulationof the occurrence and development of DN.

Key words: SET and MYND domain containing 2, diabetic nephropathy, epithelial?mesenchymal transformation, transforming growth factor beta 1