转化生长因子β1与白细胞介素-10抗纤维化作用之间的关系
Relationship between transforming growth factor beta1 and anti-fibrotic effect of interleukin-10.
作者信息
Shi Mei-Na, Huang Yue-Hong, Zheng Wei-Da, Zhang Li-Juan, Chen Zhi-Xin, Wang Xiao-Zhong
机构信息
Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China.
出版信息
World J Gastroenterol. 2006 Apr 21;12(15):2357-62. doi: 10.3748/wjg.v12.i15.2357.
AIM
To study the effect of interleukin-10 (IL-10) on the expression of transforming growth factor beta1 (TGF-beta1) in hepatic fibrosis rats and the anti-fibrotic role of exogenous IL-10.
METHODS
Hepatic fibrosis was induced by carbon tetrachloride administered (CCl(4)) intraperitoneally. The experiment was performed in two stages. In the first stage, 60 SD rats were divided randomly into normal control group 1 (GN(1), n=8), hepatic fibrosis group (GC, n=28)and IL-10 intervened group (GI, n=24). At the beginning of the 7(th) and 11(th) wk, hepatic stellate cells (HSCs) were isolated, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were performed to detect the expression of TGF-beta1 in HSCs. Histological examination was used to determine the degree of hepatic fibrosis. In the second stage, 47 SD rats were divided randomly into normal control group 2 (GN(2), n=6)and CCl(4) group(GZ, n=41). At the end of the 9(th) wk, rats in GZ group were allocated randomly into model group(GM, n=9), IL-10 treatment group (GT, n=9)and recovered group (GR, n=9). At the end of the 12(th) wk, all rats were sacrificed. RT-PCR and immunohistochemistry were performed to detect the expression of TGF-beta1 in liver tissue. ELISA was used to assay serum TGF-beta1 levels.
RESULTS
Hepatic fibrosis developed in rats with the increase of the injection frequency of CCl(4). In the first stage, hepatic fibrosis developed and HSCs were isolated successfully. At the 7(th) and 11(th) wk, TGF-beta1 mRNA in GC group increased significantly compared with that in GN(1) (P=0.001/0.042) and GI groups (P=0.001/0.007), whereas there was no significant difference between the two groups. The levels of TGF-beta1 at the beginning of the 7(th) wk was higher than that of the 11(th) wk (P=0.049). Immunocytochemistry results of TGF-beta1 were consistent with the above findings. In the second stage, TGF-beta1 increased significantly in GM group compared to GN(2). After treatment with IL-10, TGF-beta1 declined obviously. The expression of TGF-beta1 decreased in GR group but was still higher than that in GT group.
CONCLUSION
The levels of TGF-beta1 are increased in hepatic fibrosis rats and decreased after treatment with exogenous IL-10. IL-10 may play an anti-fibrotic role by suppressing TGF-beta1 expression.
目的
研究白细胞介素 -10（IL -10）对肝纤维化大鼠转化生长因子β1（TGF -β1）表达的影响以及外源性IL -10的抗纤维化作用。
方法
通过腹腔注射四氯化碳（CCl₄）诱导肝纤维化。实验分两个阶段进行。第一阶段，将60只SD大鼠随机分为正常对照组1（GN₁，n = 8）、肝纤维化组（GC，n = 28）和IL -10干预组（GI，n = 24）。在第7周和第11周初，分离肝星状细胞（HSCs），采用逆转录 - 聚合酶链反应（RT - PCR）和免疫细胞化学检测HSCs中TGF -β1的表达。组织学检查确定肝纤维化程度。第二阶段，将47只SD大鼠随机分为正常对照组2（GN₂r，n = 6）和CCl₄组（GZ，n = 41）。在第9周结束时，GZ组大鼠随机分为模型组（GM，n = 9）、IL -10治疗组（GT，n = 9）和恢复组（GR，n = 9）。在第12周结束时，处死所有大鼠。采用RT - PCR和免疫组织化学检测肝组织中TGF -β1的表达。酶联免疫吸附测定（ELISA）法检测血清TGF -β1水平。
结果
随着CCl₄注射频率增加，大鼠出现肝纤维化。第一阶段，肝纤维化形成且成功分离出HSCs。在第7周和第11周时,GC组TGF -β1 mRNA水平显著高于GN₁组（P = 0.00¹/0.042）和GI组（P = 0.00¹/0.007），而GI组与GN₁组之间无显著差异。第7周初TGF -β1水平高于第11周（P = 0.049）。TGF -β1免疫细胞化学结果与上述结果一致。第二阶段，GM组TGF -β1水平显著高于GN₂组。经IL -10治疗后，TGF -β1明显下降。GR组TGF -β1表达降低，但仍高于GT组。
结论
肝纤维化大鼠TGF -β1水平升高,外源性IL -10治疗后降低。IL -10可能通过抑制TGF -β1表达发挥抗纤维化作用。
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