雷帕霉素对肝脏缺血再灌注损伤修复的影响

The Effect of Rapamycin on Repair of Liver Ischemia/Reperfusion Injury

目的应用小鼠肝脏缺血损伤模型研究雷帕霉素对损伤肝脏修复的延迟作用并初步探讨其机制。方法建立Balb/c小鼠肝左中叶缺血损伤模型。将实验小鼠随机分为4组,A组(n=16):雷帕霉素手术组;B组(n=16):生理盐水手术组;C组(n=12):雷帕霉素假手术组;D组(n=12):生理盐水假手术组。给药后第4天对各组小鼠行手术及假手术处理。术后第1天、第4天分批处死各组动物,取出损伤肝组织作组织病理学检测;免疫组织化学方法检测组织内增殖细胞核抗原(PCNA)及细胞周期蛋白D1(CyclinD1)的表达。结果①在术后各检测时间点,A组小鼠肝组织病理学变化明显重于B组,表现为肝细胞有明显肿胀变性,肝板结构紊乱,肝窦结构不清晰,伴有肝细胞坏死;C组及D组未见明显组织病理损伤。②在各时间点,A组小鼠肝组织中PCNA阳性率显著低于B组;而且CyclinD1的阳性率也低于B组,差异有统计学意义(均P<0.05)。C组及D组未见明显PCNA及CyclinD1的表达。结论雷帕霉素阻抑了缺血再灌注损伤肝脏的修复过程,而对正常肝脏无明显损伤作用。

Objective To investigate the effect of rapamycin on repair of liver in the mouse ischemia/reperfusion model. Methods The left median lobe ischemia/reperfusion operation was performed on the Balb/c mice. The experimental mice were randomly divided into 4 groups：（1） rapamycin＋operation group（A, n=16）： The mice were dministered with rapamycin and subjected to operation at day 4; （2） normal saline＋operation group（B, n=16） ： The mice were administered with normal saline and subjected to operation at day 4;（3） rapamycin＋sham operation group（C, n= 12） ： The mice were administered with rapamycin and subjected to the sham operation at day ,1;（4） normal saline＋sham operation group（D, n= 12）： No treatment was given to the mice. Histological changes were observed on the postoperative day 1 and 4. The expression of proliferating cell nuclear antigen and Cyelin D1 in the liver was detected by immunohistoehemistry. Results At time points after operation, histological changes in group A was more severe than in group B. No Histological changes were observed in group C and group D. The expression of proliferating cell nuclear antigen and Cyclin D1 in group A was obviously lower than that in group B （P〈 0.05）. No expression of proliferating cell nuclear antigen and Cyclin D1 was detectable in both group C and group D. Conclusion Rapamyein can depress the recovery of liver injury, but do not harm to the normal liver tissue.