热休克预处理对对乙酰氨基酚所致小鼠急性肝损伤的保护作用

目的探讨热休克预处理对对乙酰氨基酚(AAP)诱导的小鼠急性肝损伤的保护作用。方法40℃分别热休克(HS)处理小鼠10min(HS10组)、20min(HS20组)和30min(HS30组),室温恢复8h后,小鼠ip给予AAP 550mg·kg-1诱导急性肝损伤,分别于AAP后0,6,24,42和72h进行相关指标检测。赖氏法检测小鼠血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性,HE染色进行病理学分析,免疫组化法检测给予AAP后0 h,小鼠肝热休克蛋白70(HSP70),细胞色素P4501A2(CYP1A2)和增殖细胞核抗原(PCNA)的表达,Western印迹法检测给予AAP后0,6,24,42和72h时小鼠PCNA的表达。结果与AAP对照组相比,HS20组小鼠血清中AST和ALT酶活水平显著降低(P<0.05),而HS10组和HS30组小鼠无显著差异。与AAP对照组相比,HS20显著降低了AAP诱导的小鼠肝损伤程度(P<0.05),而HS10和HS30未显著降低肝损伤的程度。HS20显著诱导了小鼠肝HSP70(P<0.01),CYP1A2(P<0.01)和PCNA(P<0.05)的表达,而HS10和HS30显著诱导了小鼠肝HSP70和CYP1A2(P<0.05)的表达,但未明显诱导PCNA的表达。与HS10和HS30相比,HS20更加显著地诱导了HSP70和CYP1A2的表达(P<0.05)。HS20组小鼠在注射AAP后0,6,24,42和72h,小鼠肝PCNA的表达均显著高于AAP对照组(P<0.05)、HS10和HS30组(P<0.05)。结论 40℃热休克预处理20min可以有效降低AAP诱导的小鼠急性肝损伤程度,加速肝损伤后的修复。

Protective effect of heat shock pretreatment on acute liver injury induced by acetaminophen in mice

OBJECTIVE To explore the protective effect of heat shock pretreatment on acute liver injury induced by acetaminophen (AAP) in mice. METHODS Mice received heat shock preconditioning at 40℃ for 10 min (HS10), 20 min (HS20), 30 min (HS30) and recovered at room temperature for 8 h. Then actue liver injury was induced after mice were ip given AAP 550 mg·kg^-1. The relevant indicators were detected in mice at 0, 6, 24, 42 and 72 h after AAP injection. HE staining was used to analyze the pathology in mice. The expression level of heat shock protein 70 (HSP70), cytochrome P4501A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry in mice at 0 h after AAP administration. The expression level of PCNA was also detected at 0, 6, 24, 42 and 72 h after AAP injection by Western blotting. RESULTS Compared with AAP control group, the serum aspartate aminotransaminase (AST) and alanine transaminase (ALT) levels in HS20 group significantly decreased (P<0.05), but there was no signifcant difference in HS10 and HS30 groups. HS20 significantly reduced liver injury (P<0.05), but HS10 and HS30 did not remarkably reduce liver injury after AAP injection. The expression of HSP70, CYP1A2 (P<0.01) and PCNA (P<0.05) was remarkably induced in livers of HS20 group. HSP70 and CYP1A2 (P<0.05) were significantly induced in HS10 and HS30 groups, but PCNA was not significantly induced in HS10 and HS30 groups. The expression of HSP70 and CYP1A2 in HS20 group was higher than those in HS10 and HS30 groups (P<0.05). Its expression of PCNA was significantly higher than that in AAP control group, HS10 and HS30 groups at 0, 6, 24, 42 and 72 h after AAP injection (P<0.05). CONCLUSION Heat shock pretreatment at 40℃ for 20 min can reduce liver injury induced by AAP and accelerate liver repair in mice.