A natural process of cirrhosis resolution and deceleration of liver regeneration after thioacetamide withdrawal in a rat model
A natural process of cirrhosis resolution and deceleration of liver regeneration after thioacetamide withdrawal in a rat model
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大鼠模型中硫代乙酰胺戒断后肝硬化消退和肝再生减慢的自然过程
DOI：
10.1007/s11033-010-0281-1
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发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Jiang, Guo-Liang
中科院分区：
文献类型：
--
作者：
Gu, Ke;Zhao, Jian-Dong;Jiang, Guo-Liang
作为TAA诱导肝硬化大鼠部分肝脏照射的放射生物学研究的一部分，我们观察了TAA停药后120天大鼠硫代乙酰胺（TAA）诱导肝硬化的特征。肝硬化和再生的自然过程被记录为解释部分肝脏照射研究结果的基线条件。0.03% TAA水灌胃29周，成功诱导大鼠肝硬化，造模率96%。建立肝硬化模型后，观察TAA停药120 d后大鼠肝硬化及再生的动态变化。观察到以下特点：(1)组织学改变；(2)肝功能；(3)肝硬化：三色染色，定量测定水解肝组织羟脯氨酸和tgf - β 1；(4)肝再生：流式细胞术检测肝脏指数、肝细胞有丝分裂指数（MI）、肝细胞增殖指数（PI）、免疫组化检测PCNA标记指数（LI）和PCNA mRNA表达；(5)生长因子：血清HGF、VEGF、tgf - α、IL-6。停用TAA后，肝功能逐渐改善，ALT、AST、ALP下降，PA升高。组织学改善，胶原纤维减少，tgf - β 1 IHC指数降低，三色染色和羟脯氨酸含量降低，肝硬化明显消退。然而，TAA停药后120天肝硬化仍然存在。TAA停药后肝脏再生明显减慢，表现为心肌梗死（MI）和PI降低，PCNA mRNA和PCNA LI表达降低。结论：停用TAA后，肝硬化持续缓解，但持续120天，肝脏再生明显减慢。
Characteristics of thioacetamide (TAA)-induced liver cirrhosis in rat was observed for 120 days after TAA withdrawal as part of the radiobiological study of partial liver irradiation on TAA-induced cirrhotic rats. The natural process focused on cirrhosis and regeneration was recorded as a baseline condition for the interpretation of the outcome of the partial liver irradiation study. Cirrhosis in rats was successfully induced by drinking 0.03% TAA water orally for 29 weeks with a modeling rate of 96%. After establishment of the cirrhosis model, the rats were observed for 120 days upon TAA withdrawal to investigate the dynamic changes of cirrhosis and regeneration. The following characteristics were observed: (1) Histological changes; (2) Liver functions; (3) Cirrhosis: trichrome stain, quantification of hydroxyproline in hydrolysed liver tissue and TGF-beta 1; (4) Liver regeneration: liver index, hepatocyte mitotic index (MI), hepatocyte proliferation index (PI) by flow cytometry, PCNA labeling index (LI) by IHC and expression of PCNA mRNA; and (5) Growth factors: serum HGF, VEGF, TGF-alpha, and IL-6. After TAA withdrawal, gradual improvement in liver functions was noted with decreases of ALT, AST, and ALP, and increase of PA. The resolution of cirrhosis was evident by histological improvement with attenuation of collagen fiber and decrease of TGF-beta 1 IHC index, and also decrease of trichrome stain and hydroxyproline content. However, cirrhosis was still existed on 120 days after TAA withdrawal. Significant deceleration of liver regeneration was demonstrated with TAA withdrawal, evidenced by decrease of MI and PI, reduced expression of PCNA mRNA and PCNA LI. In conclusion, upon TAA withdrawal hepatic cirrhosis was continuously resolved, but persisted up to 120 days, and liver regeneration was significantly decelerated.