摘要
目的:探讨γ-干扰素(interferon-γ,IFN-γ)影响肝脏胶原代谢的抗肝纤维化作用机制。 方法:二甲基亚硝胺腹腔注射诱导大鼠肝纤维化模型,以IFN-γ5万U/只,im,bid,共4wk。观察大鼠的体质量、肝脾重质量等一般情况.大鼠肝脏HE染色与丽春红胶原染色,分级分期观察肝组织的炎性坏死与胶原纤维沉积变化。检测大鼠血清肝功能与肝组织羟脯氨酸含量,分析肝组织间质型胶原酶(interstitial collagenase,MMP-1)活性,检测肝组织Ⅰ型前胶原[α_1(1)]基因表达。 结果:模型大鼠肝脏胶原纤维间隔形成,肝小叶与肝窦内胶原增生沉积明显;脾脏明显增大;血清ALT活性升高;肝组织羟脯氨酸含量上升,MMP-1活性轻度上升,Ⅰ型前胶原基因表达明显增多。与模型对照组比较,γ-干扰素可显著降低模型大鼠肝组织羟脯氨酸含量(29.8±11.0μg·g^(-1),vs 44.7±14.2μg·g^(-1),P<0.05),减轻肝脏内胶原纤维增生沉积,降低血清ALT活性(478.4±156.4nkat·L^(-1),vs 1055.2±128.4 nkat·L^(-1),P<0.05),提高肝组织MMP-1活性(39.8±6.5 U,vs 32.0±2.8 U,P<0.05),降低Ⅰ型前胶原基因表达(84.8±9.5％,vs 112.3±8.7％,P<0.05)。 结论:IFN-γ有良好的治疗二甲基亚硝胺诱导的大鼠肝纤维化效果,其作用机制主要在于纠正纤维化肝脏异常胶原代谢。
AIM: To investigate the mechanism of interferon-r (IFN-r) action against liver fibrosis through interfering with hepatic collagen metabolism.METHODS: A liver fibrosis model was induced by ip dimethylnitrosamine (DMN) in rats, and injected with IFN-r bid for 4 wk at a dosage of 5 × 104U per rat. The weights of body, liver and spleen were measured. The liver inflammation and collagen deposition were observed with HE and Masson' s collagen stains, analyzed with scoring and staging systems. The serum liver function and hepatic hydroxyproline (Hyp) were measured. In addition, the interstitial collagenase activity (matrix metalloproteinase, MMP-1) and pro-collagen α1 (1) gene expression were also analyzed.RESULTS:The fibrous septa were formed in the model rats, and collagens were accumulated and deposited in the sinusoids and liver lobules. The spleens enlarged, serum ALT increased, hepatic Hyp content and procollagen α1 (1) gene expression enhanced obviously and MMP-1 activity slightly increased. Compared to the control, IFN-r significantly decreased hepatic Hyp content (29.8 ± 11.0 μg· g-1vs 44.7 ± 14.2μg· g-1, P < 0.05), attenuated collagen accumulation in the fibrotic livers, and decreased the serum ALT level (478 .4 ±156.4 nkat· L-1 vs 1055.2 ± 128.4 nkat· L-1, P<0.05) and procollagen α1(1) gene expression (84.8 ±9.5 % vs 112.3 ± 8.7 %, P < 0.05), but improved the MMP-1 activity (39.8±6.5 U vs 32.0±2.8U, P<0.05).CONCLUSIONS: IFN-r has efficient actions against liver fibrosis induced by DMN in rats. The mechanism of the drug' s action is mainly associated with the adjust of abnormal collagen metabolism, inhibiting excessive hepatic collagen production and improving degradation of the deposited collagens.
出处
《世界华人消化杂志》
CAS
2002年第3期313-316,共4页
World Chinese Journal of Digestology
基金
国家自然科学青年基金
No.39700192
