Wang Aimin, Yang Xiaoming, Wang Wenxi, Zuo Fengnting, Wang Qingming, He Fuchu
Central laboratory of No. 252 Hospital of People's Liberation Army, Baoding 071000, China.
Zhonghua Yi Xue Za Zhi. 2002 May 10;82(9):610-2.
To investigate the influence of recombinant human augmenter of liver regeneration (hALR) on gene expression of tissue inhibitor of metalloproteinase-1 (TIMP1) in rat with experimental liver fibrosis.
Carbon tetrachloride was injected into the peritoneal cavities of 150 rats twice a week for 8 weeks. Albumin sensitization and caudal vein attack were conducted to another 136 rats for the duration of 3.5 months, so as to establish two kinds of animal model of experimental liver fibrosis. Recombinant hALR at different doses was given during the process of model making. Specimens of liver were taken at different time-points, then the total RNA of liver tissues was isolated and TIMP1 gene expression levels were measured by reverse transcription polymerase chain reaction.
In both rat models, TIMP(1) gene expression levels increased gradually during the process of model making. The TIMP(1) gene expression level in CCl4 model treated with low dose hALR was 0.86 +/- 0.13, 1.77 +/- 0.23, 2.78 +/- 0.36, and 3.76 +/- 0.50 respectively 2, 4, 6, and 8 weeks after the beginning of model making, all lower than those in the model group, however, without significant difference. The TIMP(1) gene expression level in CCl4 model treated with high dose hALR was 0.63 +/- 0.10, 1.18 +/- 0.20, 1.89 +/- 0.30, 2.63 +/- 0.33 respectively 2, 4, 6, and 8 weeks after the beginning of model making, significantly lower than those in CCl4 model treated with low dose hALR. In the albumin model group the TIMP(1) gene expression level showed no change during albumin sensitization, significantly increased during caudal vein attack, and reached the peak after medel making. The TIMP(1) gene expression level was lower in albumin model treated with low dose hALR during and after caudal vein attack than in the model group and negative control group, however, without significant difference (both P > 0.05). The TIMP(1) gene expression level in albumin model treated with high dose hALR was 2.33 +/- 0.36 and 4.02 +/- 0.53 during and after caudal vein attack respectively, significantly lower than those in CCl4 model group (0.99 +/- 0.14, 2.03 +/- 0.30, 2.99 +/- 0.43, and 4.13 +/- 0.44 respectively 2, 4, 6, and 8 weeks after beginning of model making respectively) and those in albumin model without hALR treatment and that with low dose hALR (4.13 +/- 0.60 and 5.99 +/- 0.83, and 3.70 +/- 0.82 and 5.63 +/- 0.89 during and after caudal vein attack respectively), and negative control group.
High dose recombinant human augmenter of liver regeneration is effective in inhibiting gene expression of TIMP(1) in experimental liver fibrosis.
探讨重组人肝再生增强因子（hALR）对实验性肝纤维化大鼠金属蛋白酶组织抑制因子-1（TIMP1）基因表达的影响。
将150只大鼠每周2次腹腔注射四氯化碳，共8周。另取136只大鼠进行白蛋白致敏和尾静脉攻击，持续3.5个月，以建立两种实验性肝纤维化动物模型。在造模过程中给予不同剂量的重组hALR。于不同时间点取肝脏标本，分离肝组织总RNA，采用逆转录聚合酶链反应检测TIMP1基因表达水平。
在两种大鼠模型中，造模过程中TIMP1基因表达水平均逐渐升高。低剂量hALR处理的CCl4模型在造模开始后2、4、6、8周时TIMP1基因表达水平分别为0.86±0.13、1.77±0.23、2.78±0.36、3.76±0.50，均低于模型组，但差异无统计学意义。高剂量hALR处理的CCl4模型在造模开始后2、4、6、8周时TIMP1基因表达水平分别为0.63±0.10、1.18±0.20、1.89±0.30、2.63±0.33，显著低于低剂量hALR处理的CCl4模型。白蛋白模型组在白蛋白致敏期间TIMP1基因表达水平无变化，尾静脉攻击期间显著升高，造模后达到峰值。低剂量hALR处理的白蛋白模型在尾静脉攻击期间及之后TIMP1基因表达水平低于模型组和阴性对照组，但差异无统计学意义（均P>0.05）。高剂量hALR处理的白蛋白模型在尾静脉攻击期间及之后TIMP1基因表达水平分别为2.33±0.36和4.02±0.53，显著低于CCl4模型组（造模开始后2、4、6、8周时分别为0.99±0.14、2.03±0.30、2.99±0.43、4.13±0.44）、未用hALR处理的白蛋白模型组及低剂量hALR处理的白蛋白模型组（尾静脉攻击期间及之后分别为4.13±0.60和5.99±0.83，3.70±0.82和5.63±0.89）以及阴性对照组。
高剂量重组人肝再生增强因子可有效抑制实验性肝纤维化中TIMP1的基因表达。
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