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MEK抑制剂U0126对大鼠睾丸移植缺血再灌注损伤的保护作用

Protective effect of MEK inhibitor (U0126) on donor testes from ischemia-reperfusion injury after orthotopic testicular transplantation in rats
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摘要 目的:探讨大鼠睾丸移植缺血再灌注损伤与细胞外信号调节激酶(ERK)表达的关系,以及MEK抑制剂(U0126)对移植睾丸的保护作用。方法:应用潭付清技术建立大鼠原位异体睾丸移植模型,将实验动物分为7组:1正常对照组;2冷灌注对照组;3假手术对照组;和应用潭付清技术建立大鼠原位异体睾丸移植模型的4睾丸移植1组(移植后30min取材);5睾丸移植2组(移植后1周取材);6U0126预处理1组(U0126预处理并在移植30min后取材);7U0126预处理2组(U0126预处理并在移植1周后取材)。Western blot法测定移植睾丸ERK1、ERK2、pERK1及pERK2的表达水平,光镜和电镜下观察组织学改变,并应用放免法测定移植受体血清T、FSH、LH值。结果:各对照组间的ERK表达、组织学改变及生殖激素水平均无显著差异(P>0.05);睾丸移植1组ERK1、ERK2、pERK1及pERK2表达水平明显高于正常对照组(P<0.05);U0126预处理1组ERK1和ERK2水平较睾丸移植1组无显著差异(P>0.05),而pERK1和pERK2水平显著低于睾丸移植1组(P<0.05);U0126预处理1组的组织学改变与正常对照组类似,但明显轻于睾丸移植1组;U0126预处理2组组织学损伤轻于睾丸移植2组,生殖激素水平与正常对照组无明显差异(P>0.05),但明显高于睾丸移植2组(P<0.01)。结论:大鼠睾丸移植后植睾ERK1、ERK2、pERK1及pERK2的表达水平明显升高,导致移植睾丸组织结构损伤和生殖激素分泌功能减退;U0126可通过抑制ERK1和ERK2磷酸化,减轻移植睾丸的早期出现的缺血再灌注损伤,短期内保护其生精功能,并维持其生殖激素水平。 Objective: To determine the effect of MEK inhibitor (U0126) on donor testes from ischemia-reperfusion injury after orthotopic testicular transplantation in rats. Methods:The rats were divided into 7 groups, Group 1 : normal control ; Group 2 : cold perfusion control ; Group 3 : sham operation control;Group 4:transplanted for 30 min;Group 5:transplanted for 1 week; Group 6:transplanted for 30 min with pretreatment of U0126;Group 7:transplanted for 1 week with pretreatment of U0126. The orthotopic testicular transplantation model was established with cuff. The levels of ERK1,ERK2,pERK1 and pERK2 of donor testes were evaluated; the change of histology and gonadal hormones were measured as well. Results: Group 1,2 and 3 had no significant differences in all results (P〉0.05). The levels of ERK1 ,ERK2 ,pERK1 and pERK2 in Group 4 were significantly increased compared with Group 1 (P〈0.05),the levels of ERK1 and ERK2 in Group 6 were not different from those of Group 4(P〉0.05),but the levels of pERK1 and pERK2 in Group 6 were lower than those in Group 4 significantly(P〈0.05),the histological changes in Group 6 were similar to Group 1 but milder than that in Group 4. The histological injury was more severe in Group 5 than that in Group 7,and the levels of gonadal hormones in Group 5 were lower than those in Group 7 (P〈0. 05)which remained at the normal levels. Conclusion: U0126 has a protective effect on the donor testes in a short period through inhibiting expression of pERK1/2 activated by testicular transplantation.
出处 《浙江大学学报(医学版)》 CAS CSCD 北大核心 2009年第1期81-88,共8页 Journal of Zhejiang University(Medical Sciences)
关键词 睾丸移植 再灌注损伤 疾病模型 动物 细胞外信号调节MAP激酶类/代谢 丝裂原激活蛋白激酶类/代谢 缺血 Testis/transpl Reperfusion injury regulated MAP kinases/metabol Ischemia Disease models,animal Extracellular signal- Mitogen-activated protein kinases/metabol
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