四氯化碳致小鼠急性肝损伤的性别差异及其与雄激素受体表达的关系

目的比较CCl4对不同性别小鼠急性肝损伤的诱导作用及其对肝脏雄激素受体(AR)表达的影响。方法健康成年昆明小鼠70只,随机分为CCl4雄性组、CCl4雌性组、雄性对照组,雌性对照组。50%CCl4-粟米油溶液皮下注射,0.6ml/100g体重,1周2次,诱导小鼠急性肝损伤。造模第7天处死各组动物取材固定,常规HE染色比较不同组别小鼠肝组织病理变化;免疫组织化学法检测各组小鼠肝脏AR的表达,根据阳性细胞反应强度及百分比设定0级(阴性)及1-3级(阳性)标准,双盲计分法统计各组AR表达分值。结果实验组CCl4造模过程中雄性组小鼠死亡率为60%(15/25),明显高于雌性组(12%,3/25),对照组小鼠无死亡(0/10,0/10)。肝组织HE染色结果可见CCl4诱导的急性肝损伤主要部位为肝小叶周围的门管区及界板区,损伤部位肝细胞出现脂肪变,少数肝组织出现点状坏死。免疫组化显示雄性及雌性对照组小鼠肝细胞AR呈弱阳性表达,不同性别小鼠肝细胞AR表达差别无统计学意义;实验组各组别肝小叶周围受损肝细胞出现较强的AR表达,其中CCl4雄性组AR表达分值明显高于CCl4雌性组小鼠(P<0.01)。结论雄性小鼠对急性肝损伤的耐受性低于雌性小鼠,其中AR的高表达与CCl4诱导的急性肝损伤性别差异密切相关。

Sex differences of the mouse hepatic injury induced by carbon tetrachloride and its correlation with the expression of androgen receptor

Objective To compare the differences of male and female mouse hepatic injury induced by carbon tetrachloride CCl4 administration and its correlation with the expression of androgen receptor. Methods 70 mice (male and female) were divided into CCl4-male group, CCl4-female group, male control group and female control group. CCl4 were injected subcutaneously 0.6 ml / 100 g body weight ( 1∶1 volume in corn oil) twice weekly. The mice were sacrificed at the 7th day. Liver pathology was evaluated by hematoxylin-eosin staining and the expression of androgen receptor in the liver was detected by immunohistochemistry. A staining index obtained according to the intensity and percentage of AR immuno-positive cells in the liver sections (values 0:negative, 1-3: positive). Results The mortality of the mice in CCl4-male group(60%,15 / 25) was higher than that of CCl4-female group (12%,3 / 25), there was no mouse dead in control groups (0 / 10). The hepatic injury induced by CCl4 was mainly appeared in the portal area around the hepatic lobule, slight steatosis and spotty necrosis was observed. AR expression can be detected in control groups with slight immuno-reaction (IR) and there was no difference between the male control group and the female control group. The score of AR-IR in CCl4-male group was significantly higher than that in CCl4-female group (P<0.05). Conclusion The male mice possess a lower tolerance to the acute liver injury than female mice do and the higher expression of AR was correlated with the sex differences of hepatic injury induced by CCl4.