FVB小鼠急性缺血再灌注肾损伤中CHOP蛋白作用的探讨

Renal acute ischemia-reperfusion injury in FVB mice:an involvement of CHOP

目的通过对比ICR、FVB两种小鼠肾脏急性缺血再灌注后的差异，探索导致肾脏急性缺血再灌注损伤的关键致病分子，并探讨其可能机制。方法将ICR、FVB两种小鼠（雄性、8—10周龄）各随机分为模型组和正常对照组（n=12），两种小鼠的模型组采用相同的方法建立肾脏急性缺血再灌注模型（先切除右肾再夹闭左肾肾蒂45rain），再灌注24h后收集模型组小鼠的心脏血、肾脏，检测各小鼠血浆BUN浓度，观察小鼠肾组织病理损伤的程度，Western—blot检测肾组织CHOP蛋白的表达，对照组检测同样的指标。结果（1）。肾组织PAS染色可见：ICR、FVB小鼠模型组肾小管上皮细胞损伤明显重于对照组，差异有统计学意义（P〈0．01），ICR小鼠模型组肾小管上皮细胞损伤又明显重于FVB小鼠模型组（P〈0．01）；（2）血浆BUN浓度：ICR、FVB小鼠模型组高于对照组（P〈0．01），ICR小鼠模型组高于FVB小鼠模型组（P〈0．01）；（3）Western—blot：ICR、FVB小鼠模型组CHOP蛋白的表达量高于对照组（P〈0．01），ICR小鼠模型组CHOP蛋白的表达量高于FVB小鼠模型组（P〈0．05）。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。

Objective To explore a mouse strain that is resistant to acute ischemic kidney injury and to take a step in characterizing the molecular basis for the resistance. Methods Acute renal ischemic injury model was established in male FVB and ICR mice （8 - 10 W of age） by removing fight kidney followed by clamping left renal pedicle for 45 rain. And 24 hours after injury, blood and kidney were collected to detect concentration of blood urea nitrogen （BUN） for assessment of the degree of damage of renal pathology by PAS staining and for the detection of the expression of CHOP in renal tissue by Western-blot. Control group was tested the same indicators as the model group. Additionally, some mice （n = 12/strain） were followed for 72 hours to examine histology of kidney injury evolution. Results （ 1 ） PAS staining of renal tissue showed that kidneys were largely normal in FVB mice after 45 minutes of ischemia while severe renal tubular injury including extensive cell death and the loss of renal structure were present in ICR mice. （2） BUN levels were significant/y increased from baseline in ICR but not in FVB mice. （3） CHOP critically involved in renal tubular cell death was elevated in ischemic ICR mice kidneys but remained relatively normal in isehemic FVB mice kidneys. Conclusion In the acute renal ischemia-reperfusion injury model, the degree of renal tubular epithelial cell injury of ICR mice are more serious than FVB mice, and the expression of endoplasmic retieulum stress related protein CHOP also increases. It is indica- ted that CHOP plays an important role in acute renal ischemia-reperfusion injury. FVB mice are resistant to ischemic renal injury and the mechanism may involve the expression of CHOP protein.