禁食通过HSF1保护肝脏缺血再灌注损伤

Fasting protects mice against hepatic ischemia/reperfusion injury through HSF1

目的探讨短期禁食对肝脏缺血再灌注损伤的影响及和HSF1的关系。方法小鼠随机分为两大组8小组,第一大组为假手术组,再进一步分为4个小组:A组HSF1Alb-小鼠正常饮食,B组HSF1Alb-小鼠禁食16 h,C组HSF1Alb+小鼠正常饮食,D组HSF1Alb+小鼠禁食16 h。对照组只进行开关腹和游离左外叶不进行阻断和开放左外叶血流;第二大组为缺血再灌注组,进一步分为4个小组:E组HSF1Alb-小鼠正常饮食,F组HSF1Alb-小鼠禁食16 h,G组HSF1Alb+小鼠正常饮食,H组HSF1Alb+小鼠禁食16 h。缺血再灌注组进行小鼠左外叶30%的缺血60 min再灌注6 h实验。检测各组小鼠血清ALT、AST。通过比较各组血清转氨酶的水平以及评价肝组织病理损伤的程度,来判断短期禁食及HSF1对小鼠缺血再灌注损伤的影响。结果假手术组禁食和不禁食对血清转氨酶没有明显差别,缺血再灌注组中,HSF1Alb-小鼠禁食组的转氨酶明显低于正常饮食组,但在HSF1Alb+小鼠看不到这一明显的保护作用;HSF1Alb-小鼠禁食组的肝组织损伤明显减轻。结论禁食能明显减轻肝脏缺血再灌注损伤,禁食的肝脏缺血再灌注损伤的保护作用在HSF1-/-小鼠被消除。

Objective To investigate the effect of short-term fasting on hepatic ischemia/reperfusion （IR）injury and its relationship with heat shock factor 1 （HSF1 ）.Methods A hepatic ischemia/reperfusion model was built.The left lateral liver was subjected to 60 minutes of ischemia followed by 6 hours of reperfusion,then the left liver and blood was collected.Male HSF1Alb-and HSF1Alb＋ mice were randomly divided into 2 groups：control group （with false operation）;IR group,which were subjected to ischemia for 60min and reperfusion for 6h.Furthermore,both groups were divided into 4 subgroups according to the fasting and HSF1Alb.Levels of alanine aminotransferase and aspartate aminotransferase,as well as HE staining,in the four subgroups were compared,respectively.Results Fasting dramatically reduced the injury of ischemia/reperfusion,but in HSF1 knockout mice fasting could not alleviate the injury.Conclusion Fasting protected mice against hepatic ischemia/reperfusion injury,in which HSF1 was indispensable.