FVB小鼠肾脏对急性缺血再灌注损伤的抗性及其分子机制

发布时间：2018-04-11 03:24

  本文选题：急性肾缺血再灌注损伤 + 内质网应激　； 参考：《福建医科大学》2014年硕士论文

【摘要】：目的： 肾脏急性缺血再灌注损伤是临床非常重要的一个问题。目前对于其发病机理还缺乏认识，因此也还没有找到有针对性的有效治疗措施。本课题通过寻找到对肾脏急性缺血再灌注损伤存在抗性的小鼠种系，通过与容易发生损伤的小鼠肾脏进行比较来探索导致肾脏急性缺血再灌注损伤的关键的致病分子，目的是在了解肾脏急性缺血再灌注损伤分子发病机制的基础上研发靶向治疗药物。 方法： 将FVB、ICR两种小鼠（雄性♂、8-10W）各随机分为正常组和模型组(n=6)，两种小鼠模型组应用先切除右肾再夹闭左肾肾蒂45min的方法来建立急性肾缺血再灌注损伤模型，再灌注24小时后收集模型组小鼠的心脏血、肾脏，应用脲酶法检测各小鼠血浆BUN浓度，采用PAS染色观察小鼠肾组织病理损伤的程度，PCR、 Western-blot检测肾组织chop mRNA、CHOP蛋白的表达，正常组检测同样的指标。 结果： （1）肾组织PAS染色可见：FVB、ICR小鼠模型组肾小管上皮细胞损伤明显重于正常组，有明显的统计学意义（P0.01），ICR鼠模型组肾小管上皮细胞损伤又明显重于FVB鼠模型组，有明显的统计学意义（P0.01）；（2）血浆BUN浓度：FVB、ICR小鼠模型组高于正常组，有明显的统计学意义（P0.01），ICR鼠模型组高于FVB鼠模型组，有明显的统计学意义（P0.01）；（3）PCR：各组之间chop mRNA表达无明显差异（P0.05）；（4）Western-blot：FVB、ICR小鼠模型组CHOP蛋白的表达量高于正常组，有明显的统计学意义（P0.01），ICR小鼠模型组CHOP蛋白的表达量高于FVB鼠模型组（P0.05）。 结论： 在急性肾缺血再灌注损伤模型中ICR小鼠肾小管上皮细胞损伤程度明显重于FVB小鼠，内质网应激相关蛋白CHOP表达也明显上调，提示CHOP在急性肾缺血再灌注损伤中发挥了重要的作用，，FVB小鼠对急性肾缺血再灌注损伤存在抗性，机制可能与CHOP蛋白的表达有关。
[Abstract]:Objective:Acute renal ischemia reperfusion injury is a very important clinical problem.At present, there is a lack of understanding of its pathogenesis, so no targeted and effective treatment has been found.In this study, we find the strain of mice resistant to acute renal ischemia-reperfusion injury, and explore the key pathogenic molecules that lead to acute renal ischemia-reperfusion injury by comparing them with those prone to renal injury.The aim of this study was to investigate the molecular pathogenesis of acute renal ischemia reperfusion injury.Methods:Two kinds of mice (male) were randomly divided into two groups: normal group and model group. The models of acute renal ischemia-reperfusion injury were established by removing the right kidney and then clipping the left kidney pedicle 45min.After 24 hours of reperfusion, the heart blood and kidney of the model group were collected. The plasma BUN concentration of each mouse was detected by urease method. The degree of renal pathological injury was observed by PAS staining. The expression of chop mRNA-chop protein in renal tissue was detected by Western-blot.The same index was detected in the normal group.Results:(1) PAS staining of renal tissue showed that the injury of renal tubular epithelial cells in the PAS group was significantly more serious than that in the normal group, and the injury of renal tubular epithelial cells in the model group was significantly more serious than that in the FVB model group.There was significant statistical significance (P 0.01) the plasma BUN concentration in the model group was higher than that in the normal group, and it was significantly higher in the model group than that in the FVB group.There was no significant difference in the expression of chop mRNA between the two groups. The expression of CHOP protein in the Western-blot1: FVB-ICR model group was higher than that in the normal group, and the expression of CHOP protein in the P0.01 / FVB model group was significantly higher than that in the FVB model group (P0.05).Conclusion:In acute renal ischemia-reperfusion injury model, the injury degree of renal tubular epithelial cells in ICR mice was significantly greater than that in FVB mice, and the expression of endoplasmic reticulum stress-related protein (CHOP) was up-regulated.The results suggest that CHOP plays an important role in acute renal ischemia-reperfusion injury. FVBmice are resistant to acute renal ischemia-reperfusion injury, and the mechanism may be related to the expression of CHOP protein.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692


本文编号：1734215