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尼替西农对酪氨酸血症Ⅰ型所致肝损伤的保护作用

作者：孙利平 1 常彦祥 2

单位：1.渭南职业技术学院陕西渭南 714000 2.西安医学院第一附属医院胸外肿瘤科西安 710038

关键词：尼替西农 Fah -/- 小鼠酪氨酸血症Ⅰ型肝功能损伤

分类号：

出版年,卷(期):页码：2017,9(3):45-49

摘要：

摘要：目的研究尼替西农对于酪氨酸血症Ⅰ型所致肝损伤的保护作用。方法选取野生型小鼠为健
康对照组（A组，10只），将40只Fah -/- 小鼠随机分为4组（B～E组），每组10只。B组给予尼替西农
0.2 mg/（kg·d），共给药5周，C组给予尼替西农0.2 mg/（kg·d），共给药4周，第5周给予等量生理盐
水，D组给予尼替西农0.2 mg/（kg·d），共给药1周，后4周给予等量生理盐水，A组和E仅给予等量生
理盐水，观察分析治疗期间小鼠的健康状态、体重、血清学指标（ALT、AST和ALP）以及肝组织病
理学变化。结果 B组小鼠的生物化学指标与肝脏组织学改变与A组无显著差异，C、D组停药后小鼠
血清学指标逐渐上升，病理学显示肝脏有一定的损伤，E组小鼠血清学指标持续上升，体重下降，病
理学显示肝脏损伤严重。A～E组小鼠肝组织炎症评分分别为（1.00 ± 0.00）分、（1.19 ± 0.11）分、
（2.09 ± 0.23）分、（3.41 ± 0.31）分和（3.96 ± 0.23）分，其中C组、D组和E组评分显著高于A组，
差异有统计学意义（t值分别为4.241、5.751、6.892，P值分别为0.032、0.021、0.006），B组评分与A
组相比差异无统计学意义（t = 0.512，P = 0.223）。A～E组小鼠肝组织坏死评分分别为（1.00 ± 0.00）
分、（1.07 ± 0.13）分、（2.45 ± 0.26）分、（3.37 ± 0.33）分和（3.76 ± 0.26）分，其中C组、D组和E
组评分显著高于A组，差异有统计学意义（t值分别为4.451、5.669、6.983，P值分别为0.030、0.023、
0.005），B组评分与A组相比差异无统计学意义（t = 0.471，P = 0.269）。结论尼替西农对酪氨酸血
症Ⅰ型所致肝损伤具有良好的保护作用。

Abstract: Objective To evaluate the protective effects of nitisinone on liver injury caused by tyrosinemia
type Ⅰ. Methods Total of 10 wild type mice were selected as healthy controls (group A) and 40 Fah -/- mice
were divided into four groups (group B～E), 10 mice in each group. Mice in group B were given nitisinone
0.2 mg/(kg·d) for 5 weeks, mice in group C were given nitisinone 0.2 mg/(kg·d) for the first 4 weeks and
equivalent normal saline for the last one week, mice in group C were given nitisinone 0.2 mg/(kg·d) for one
week and equivalent normal saline for the last 4 weeks, mice in group A and E were given equivalent normal
saline for 5 weeks. The health status, body weight, serology indexes (ALT, AST and ALP) and pathological
changes of liver tissue in mice were analyzed. Results The serology indicators and liver histologic changes
of mice in group B had no significant differences compared with group A. The serology indicators of mice in
group C and D increased gradually when the nitisinone were stopped given. The serology indicators of mice
in group E increased and body weight decreased, the pathology showed that the liver were damaged severely.
The liver inflammation scores of groups A～E were 1.00 ± 0.00, 1.19 ± 0.11, 2.09 ± 0.23, 3.41 ± 0.31 and
3.96 ± 0.23, respectively. The scores of group C, D and E were significantly higher than that of group A,
the differences were statistically significant (t = 4.241, 5.751, 6.892, P = 0.032, 0.021, 0.006). There was no
significant difference of liver inflammation score between group A and B (t = 0.512，P = 0.223). The liver

necrosis scores of groups A～E were 1.00 ± 0.00, 1.07 ± 0.13, 2.45 ± 0.26, 3.37 ± 0.33 and 3.76 ± 0.26,
respectively. The scores of group C, D and E were significantly higher than that of group A, the differences
were statistically significant (t = 4.451, 5.669, 6.983, P = 0.030, 0.023, 0.005).There was no significant
difference of liver necrosis score between group A and B (t = 0.471，P = 0.269). Conclusion Nitisinone had
a good protective effect on liver injury caused by tyrosinemia type Ⅰ.

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