17α-乙炔雌二醇诱导胆汁淤积性肝损伤大鼠模型评价

Evaluation on a rat model with cholestatic liver injury induced by 17α-ethynylestradiol

目的研究不同给药周期下17α-乙炔雌二醇(17α-ethynylestradiol,EE)诱导大鼠胆汁淤积性肝损伤的病理特征和严重程度,探讨造模的最佳给药周期。方法采用雄性SD大鼠,每日以5 mg/kg的EE丙二醇溶液进行皮下注射,分别在给药2 d、5 d、8 d、12 d、16 d观察大鼠一般情况,分批处死并取大鼠血清和肝脏,测定肝指数、肝脏病理组织学变化及血清生化指标。结果与对照组相比,随着EE给药周期的延长,大鼠毛色逐渐呈现发黄,凌乱无光泽,肝肿大明显,肝指数均呈现显著性增加;病理学结果显示,随着造模周期的增加,部分肝细胞出现核膜固缩,肝细胞轻微水肿,随后出现空泡样变性和坏死,部分区域存在炎性浸润,然而上述现象或指标在造模5 d的程度较为严重,即使给药周期延长,严重程度并未显著增加。血清生化结果显示,碱性磷酸酶(AKP)和总胆汁酸(TBA)在造模2 d最先出现异常,而谷丙转氨酶(ALT)活性和谷草转氨酶(AST)在造模5 d才显著升高(P <0. 05);上述指标在5 d时达到最大值,随着EE给药周期的延长,其值并未进一步增加,与5 d时相比,差异无统计学意义(P> 0. 05)。结论 EE皮下注射可以诱导典型的胆汁淤积性肝损伤,造模周期以给药5 d较佳。

Objective To study the pathological features and severity of cholestatic liver injury induced by 17α- ethynylestradiol (EE) in rats under different dosing cycles, and to explore the optimal dosing cycle for modelling. Methods SD rats were injected subcutaneously with 5 mg/kg EE propylene glycol solution every day for 2 days, 5 days , 8 days, 12 days, and 16 days. The general condition of the rats was observed. The rats were sacrificed after different dosing cycles . Rat serum and liver tissues were measured for liver index, liver histopathological changes and serum biochemical indicators. Results Compared with the control group, with extended dosing periods of EE injection, the hair color of the rats gradually appeared yellow, and was disorderly and dull, hepatomegaly was obvious, and the hepatic index showed a significant increase;the pathological results showed that with the prolonged administration of modeling cycles, the nuclear membrane of some hepatocytes contracted, slight edema of hepatocytes could be seen, and then followed by vacuolar degeneration, necrosis and inflammatory infiltration in some areas. However, the above phenomena and indicators were more severe on the 5th day after model establishment. Even though the administration period was prolonged, the severity did not increase significantly. The results of serum biochemistry showed that alkaline phosphatase (AKP) and total bile acid (TBA) were the first abnormalities on the 2nd day after model establishment, while ALT and AST were significantly increased on the 5th day after model establishment ( P <0.05). Above all, the above indexes reached the maximum value on the 5th day, with the prolongation of the EE dosing period, the value did not increase further. On the contrary, there was a decreasing trend, and there was no significant change compared with the 5th day ( P >0.05). Conclusion Subcutaneous injection of EE can induce typical cholestatic liver injury in rats, and the 5th day model period is preferably for EE-induced cholestasis animal models.