EZH2在大鼠睾丸扭转后缺血再灌注损伤中的作用及机制

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摘要目的探讨Zeste同源物增强子2（EZH2）在大鼠睾丸扭转复位后缺血再灌注损伤中的作用及机制。方法 18只成年健康雄性SD大鼠按照随机数字表法分为对照组、缺血组和EZH2抑制剂组，每组6只。对照组：将游离后的睾丸顺时针扭转720°后立即复位、固定；缺血组和EZH2抑制剂组：将游离后的睾丸顺时针扭转720°，维持2 h后将扭转的睾丸复位、固定。EZH2抑制剂组在扭转造模前腹腔注射EZH2抑制剂UNC1999 [50 mg/（kg·d）]，连续3 d。对照组和缺血再灌注组腹腔注射同体积磷酸缓冲盐溶液（PBS）。各组大鼠在扭转再复位4 h后处死，获取缺血后的睾丸组织，检测三组睾丸组织中的超氧化物歧化酶活性（SOD）和丙二醛（MDA）含量；苏木精-伊红染色和原位末端转移酶标记技术法观察组织病理学改变和生精细胞凋亡指数（AI）；免疫蛋白印迹检测各组睾丸组织EZH2、核因子E2相关因子2（Nrf2）、血红素氧合酶-1（HO-1）的表达水平。结果与对照组比较，缺血组和EZH2抑制剂组在睾丸复位后SOD活性下降，Nrf2、HO-1表达降低，MDA、AI、EZH2水平升高，差异均有统计学意义（均P < 0.05）。与缺血组比较，EZH2抑制剂组的SOD活性升高，Nrf2、HO-1的表达升高，MDA、AI、EZH2水平降低，差异均有统计学意义（均P < 0.05）。结论 EZH2在睾丸缺血再灌注过程中发挥重要作用，EZH2抑制剂可保护睾丸扭转复位后的缺血再灌注损伤，其机制可能是通过增强Nrf2/HO-1通路、抑制细胞凋亡来实现。

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	钟云萍张健健王磊刘修恒▲

关键词 ： Zeste同源物增强子2, 睾丸, 扭转, 缺血

Abstract：Objective To investigate the effects of EZH2 on testicular ischemia-reperfusion injury in rats. Methods Eighteen adult healthy male SD rats were randomly divided into control group, ischemia group and EZH2 inhibition group, 6 rats in each group. The free testicles were immediately repositioned and fixed after clockwise torsion of 720° in control group. The free testicles were rotated torsion of 720° and maintained for 2 h in ischemia group and EZH2 inhibition group. Before clockwising torsion, EZH2 inhibitor group was intraperitoneally injected with E2H2 inhibitor UNC1999 [50 mg/(kg·d)] for 3 days, while the control group and ischemia group were intraperitoneally injected with the phosphate buffer saline (PBS) of same volume. Rats in each group were sacrificed after 4 h of torsion and reposition, and the ischemic testicular tissues were obtained. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Histopathoiogical changes and germ cell apoptosis indices (AI) were observed using hematoxylin-eosin staining and in situ terminal transferase labeling technique. The expressions of EZH2, NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected using Western blot. Results Compared with control group, the activity of SOD and the expression of Nrf2 and HO-1 were decreased after reduction, the expressions of MD, AI and EZH2 were increased in ischemic group and EZH2 inhibitor group, the differences were statistically significant (all P < 0.05). Compared with ischemic group, the activity of SOD and the expression of Nrf2 and HO-1 were increased after reduction, the expressions of MDA, AI and EZH2 were decreased in EZH2 inhibitor group, the differences were statistically significant (all P < 0.05). Conclusion EZH2 plays an important role in testicular ischemia-reperfusion injury. EZH2 inhibitor exerts a beneficial effect of testicles torsion repositioned after ischemia-reperfusion injury. This effect may be achieved through enhancing Nrf2/HO-1 expression and inhibiting apoptosis.

Key words： Zeste homologous enhancer 2 Testicle Torsion Ischemia

基金资助:湖北省自然科学基金青年项目（2017CFB181）；
湖北省武汉市青年科技晨光计划项目（2017050304010281）。

通讯作者: ▲通讯作者

引用本文:

钟云萍张健健王磊刘修恒▲. EZH2在大鼠睾丸扭转后缺血再灌注损伤中的作用及机制[J]. 中国医药导报, 2019, 16(28): 21-24.
ZHONG Yunping ZHANG Jianjian WANG Lei LIU Xiuheng▲. Effect of EZH2 on testicular ischemia-reperfusion injury in rats. 中国医药导报, 2019, 16(28): 21-24.

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[1] 侯鸿发，苏永辉，卜巨源，等.EZH2表达与结直肠癌肿瘤细胞增殖和血管生成及预后的关系[J].中山大学学报：医学科学版，2017，38（6）：866-872.
[2] 陈松燕，郑翠苹，吴圣豪，等.DNA甲基转移酶与EZH2在急性白血病中的表达及临床意义[J].武汉大学学报：医学版，2017，38（1）：74-76，99.
[3] Yazawa H，Sasagawa I，Suzuki Y，et al. Glucocorticoid hormone can suppress apoptosis of rat testicular germ cells induced by testicular ischemia [J]. Fertil Steril，2001，75（5）：980-985.
[4] 刘卫华，邓红琴.外源性硫化氢对大鼠睾丸缺血再灌注损伤的保护作用[J].中国医药导报，2017，14（5）：25-27， 34，封4.
[5] 赵豫刚，郑新民，周吉，等.睾丸扭转复位后生精上皮细胞核转录因子表达的改变及其凋亡[J].中华医学杂志，2006（20）：1381-1385.
[6] Kapoor S. Testicular torsion：a race against time [J]. Int J Clin Pract，2008，62（5）：821-827.
[7] Lysiak JJ，Nguyen QA，Turner TT. Peptide and nonpeptide reactive oxygen scavengers provide partial rescue of the testis after torsion [J].J Androl，2002，23（3）：400-409.
[8] Filho DW，Torres MA，Bordin AL，et al. Spermatic cord torsion，reactive oxygen and nitrogen species and ischemia-reperfusion injury [J]. Mol Aspects Med，2004，25（1-2）：199-210.
[9] 胡东来，舒强.新生儿睾丸扭转的临床分析[J].中华泌尿外科杂志，2017，38（2）：118-121.
[10] Lysiak JJ，Turner SD，Nguyen QA，et al. Essential role of neutrophils in germ cell-specific apoptosis following ischemia/reperfusion injury of the mouse testis [J].Biol Reprod，2001，65（3）：718-725.
[11] 吕晓晓，姚美玲，胡晓康，等.灯盏花素对青春前期大鼠睾丸扭转复位双侧睾丸的保护作用[J].中华男科学杂志，2016，22（4）：300-305.
[12] 张华锋，赵佳，徐道明.白藜芦醇对大鼠睾丸扭转损伤的保护作用[J].中华实验外科杂志，2015，32（6）：1473.
[13] 郭晶晶，俞丽云，黄美，等.持续低流量复灌注对兔睾丸不全扭转细胞凋亡的影响[J].中国男科学杂志，2015， 29（1）：22-27.
[14] 陈聪，薛恩生，钱清富，等.靶向超声微泡造影评价低分子肝素对兔睾丸缺血再灌注损伤保护作用的实验研究[J].中国超声医学杂志，2018，34（8）：743-746.
[15] Miti■ T，Caporali A，Floris I，et al. EZH2 modulates angiogenesis in vitro and in a mouse model of limb ischemia [J]. Mol Ther，2015，23（1）：32-42.
[16] Gong C，Yao S，Gomes AR，et al. BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation and epigenetic silencing through targeting EZH2 in breast cancer [J]. Oncogenesis，2016，5：e214.
[17] 李文川，高良奎，李浩航，等.左卡尼汀通过激活Nrf2/HO-1途径减轻大鼠肝脏热缺血再灌注损伤[J].中华肝胆外科杂志，2017，23（2）：121-125.
[18] 张玉琴，李鸷，李煌，等.栝楼桂枝颗粒激活Nrf2信号通路减轻脑缺血再灌注损伤大鼠氧化应激损伤作用[J].中国实验方剂学杂志，2017，23（21）：112-116.
[19] 贾宝超，关键，戴辛鹏，等.Nrf2、HO-1在口腔鳞癌组织中的表达及其临床意义[J].口腔医学研究，2017，33（2）：207-210.
[20] 滕志朋，余天平，王晨，等.人脑胶质母细胞瘤中Nrf-2和HO-1的表达及意义[J].临床与实验病理学杂志，2012， 28（9）：1011-1014.