[1]赵艳龙,田普训△,程小红△,等.地西他滨对小鼠肾缺血再灌注损伤作用的实验研究*[J].陕西医学杂志,2020,49(3):267-273,278.
　ZHAO Yanlong,TIAN Puxun,CHENG Xiaohong,et al.Effects of decitabine on renal ischemia reperfusion injury[J].,2020,49(3):267-273,278.
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地西他滨对小鼠肾缺血再灌注损伤作用的实验研究*
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
49
期数:
2020年3期
页码:
267-273,278
栏目:
基础研究
出版日期:
2020-03-05

文章信息/Info

Title:
Effects of decitabine on renal ischemia reperfusion injury
文章编号:
DOI:〖HT5K〗10.3969/j.issn.10007377.2020.03.003
作者:
赵艳龙1; 田普训2△; 程小红3△; 丁晨光2; 田 耘3; 于小勇3; 史 健3; 徐 薇3; 张 鹏3; 宋阿苗3
1.陕西省中医医院肾病医院血液透析室(西安710003); 2.西安交通大学第一附属医院肾脏病医院肾移植科(西安710061); 3.陕西省中医医院肾病医院肾病科(西安710003)
Author(s):
ZHAO Yanlong; TIAN Puxun; CHENG Xiaohong; et al.
Department of Hemodialysis,Hospital of Nephropathy,Shaanxi Traditional Chinese Medicine Hospital(Xi'an 710003)
关键词:
地西他滨;  肾脏;  缺血再灌注损伤;  调整性T淋巴细胞;  M2型巨噬细胞;  小鼠
Keywords:
Decitabine;  Kideny;  Ischemia reperfusion injury;  Treg;  M2 macrophages;  Mice
分类号:
R392.5
文献标志码:
A
摘要:
目的:探讨DNA甲基转移酶抑制剂地西他滨对小鼠肾缺血再灌注损伤的影响。方法:体外MTT法检测地西他滨对小鼠肾小管上皮细胞(HK-2)增殖的影响,流式细胞仪检测地西他滨是否可诱导HK-2细胞凋亡及对缺氧-复氧诱导的HK-2细胞凋亡的影响; 地西他滨预处理C57BL/6小鼠4d,建立肾缺血再灌注损伤模型(IRI),地西他滨继续干预2d后检测肾功,采用HE染色观察肾组织病理变化,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)评估肾小管上皮细胞的凋亡、增殖细胞核抗原(PCNA)的免疫荧光染色检测小管细胞增值,免疫组化检测肾组织嗜中性粒细胞浸润、流式细胞仪分析肾组织调整性T细胞(Treg)、M2型巨噬细胞表达。结果:随浓度增加,地西他滨抑制HK-2细胞增殖及诱导其凋亡作用明显增强(P<0.01或0.05),低剂量地西他滨可抑制缺氧-复氧诱导的HK-2凋亡(P<0.01),改善肾IRI小鼠肾功(P<0.01)及病理损伤(P<0.05),抑制肾小管上皮细胞的凋亡(P<0.01),减少肾组织内炎性嗜中性粒细胞浸润(P<0.01),增加免疫调整性T淋巴细胞(Treg)及M2型巨噬细胞表达(P<0.01)。结论:地西他滨通过抑制肾小管上皮细胞凋亡、肾组织炎细胞浸润,对小鼠肾缺血再灌注损伤发挥保护作用,地西他滨可能成为干预肾IRI的新策略。
Abstract:
Objective:To investigate the effects of DNA methyltransferase inhibitor decitabine(DCA)on renal ischemia reperfusion injury(IRI). Methods:The effects of DCA on proliferation of renal tubular epithelial cells(HK-2)were detected by MTT. HK-2 apoptosis,induced by different concentration DCA and anoxic reoxygenation,was determined by flow cytometer. In vivo,DCA intervention was applied 4 days before and 2 days after IRI modeling in male C57BL/6 mice. The renal function,renal pathological trauma,tubular cells apoptosis and proliferation,renal neutrophils infiltration,renal expressions of Tregs and M2 macrophages were detected by biochemical analyzer,hematoxylin and eosin(HE)staining,TUNEL assay,immunofluorescent staining,immunohistochemistry and flow cytometry,respectively. Results:The inhibition of HK-2 cells proliferation and induction of apoptosis by DCA were significantly increased with increasing concentration(P<0.01 or 0.05). Low-dose DCA decreased HK-2 apoptosis induced by anoxic reoxygenation(P<0.01). In vivo,DCA also protected against renal IRI and decreased tubular cells apoptosis(P<0.01 or 0.05). Meanwhile,DCA suppressed neutrophils infiltration(P<0.05)and increased expressions of Tregs and M2 macrophages in the renal after IRI(P<0.01).Conclusion:DCA effectively protect against renal IRI by reducing tubular cells apoptosis and inflammation cells infiltration. DCA may become a therapeutic strategy for renal IRI.

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备注/Memo

备注/Memo:
*国家自然科学基金资助项目(81873176,81870514)
更新日期/Last Update: 2020-03-25