CAJ | 학술논문

目的观察γ-干扰素(IFN-γ)对四氯化碳(CCl4)诱导的大鼠肝纤维化的治疗效果,并探讨其可能的机制.方法 30只雄性大鼠用CCl4诱导致肝纤维化,随机分成2组(模型组、IFN-γ治疗组),连续用药12周,观察肝组织病理、血清透明质酸(hyaluronic acid,HA)、血清转化生长因子β1(transforming growth factor β1,TGF-β1)、肝组织切片TGF-β1、转化生长因子βⅠ型受体(transforminggrowth factor β receptor,TβR-Ⅰ)、Smad2/3的表达.结果 ①肝组织病理:与正常组比较,模型组大鼠肝组织都有不同程度的炎症和纤维化产生.模型组纤维化程度较正常对照组明显,差异有统计学意义(P＜0.05)；γ-干扰素治疗组纤维化程度较模型组显著改善,差异有统计学意义(P＜0.05)；②肝纤维化指标(HA、TGF-β1):γ-干扰素治疗组大鼠HA及TGF-β1较模型组均降低(P＜0.05),③TGF-β1/Smad基因蛋白:免疫组织化学检测显示,与模型组相比,IFN-γ治疗组大鼠肝脏中TGF-β1、TβR-Ⅰ和Smad2/3蛋白表达均显著减弱,差异有统计学意义(P＜0.05).结论 IFN-γ治疗组具有显著抗肝纤维化作用,对TGF-β1/Smad信号转导通路的影响可能为其作用机理之一.
목적 관찰γ-간우소(IFN-γ)대사록화탄(CCl4)유도적대서간섬유화적치료효과,병탐토기가능적궤제.방법 30지웅성대서용CCl4유도치간섬유화,수궤분성2조(모형조、IFN-γ치료조),련속용약12주,관찰간조직병리、혈청투명질산(hyaluronic acid,HA)、혈청전화생장인자β1(transforming growth factor β1,TGF-β1)、간조직절편TGF-β1、전화생장인자βⅠ형수체(transforminggrowth factor β receptor,TβR-Ⅰ)、Smad2/3적표체.결과 ①간조직병리:여정상조비교,모형조대서간조직도유불동정도적염증화섬유화산생.모형조섬유화정도교정상대조조명현,차이유통계학의의(P＜0.05)；γ-간우소치료조섬유화정도교모형조현저개선,차이유통계학의의(P＜0.05)；②간섬유화지표(HA、TGF-β1):γ-간우소치료조대서HA급TGF-β1교모형조균강저(P＜0.05),③TGF-β1/Smad기인단백:면역조직화학검측현시,여모형조상비,IFN-γ치료조대서간장중TGF-β1、TβR-Ⅰ화Smad2/3단백표체균현저감약,차이유통계학의의(P＜0.05).결론 IFN-γ치료조구유현저항간섬유화작용,대TGF-β1/Smad신호전도통로적영향가능위기작용궤리지일.
Objective To study the impact of IFN-γ on liver fibrosis and its possible mechanism.Methods Thirty healthy male SD rats were randomly divided into two groups:fibrosis model group,IFN-γ treatment group.Experimental liver fibrosis was induced by subcutaneous injection of CCl4.After 12-week-treatment,serum hyalurnic acid and TGF-β1 was examined,histopathological changes and degrees of fibrosis were observed by optical microscopy.Meanwhile,the expression of TGF-β1,TβR-Ⅰ and Smad2/3 proteins was detected by immunohistochemistry and quantified by using computerized image analysis.Results ① Pathological observation of hepatic specimens:histological examination showed that there were significant difference between normal group and fibrosis model group by comparing with the degrees of inflammation and fibrosis(P ＜ 0.05).And the difference between fibrosis model group and IFN-γ treatment group was significant(P ＜ 0.05).②Changes of the hepatic fibrosis index (serum HA and TGF-β1):the levels of serum HA,TGF-[β1 in fibrosis model group were higher than IFN-γ treatment groups(P ＜ 0.05).③Changes of gene protein levels about TGF-β/Smad:the expressions of TGF-β1,TβR-Ⅰ and Smad2/3 in rat hepatic tissue were detected with immunohistochemistry techniques.The expressions of the three items in model group were higher than normal group(P ＜0.01).The difference between model group and IFN-γ treatment group was significant (P ＜ 0.05) ; Conclusion IFN-γ treatment group had significant results on treating experimental hepatic fibrosis.By the way of inhibiting expressions of TGF-β1,TβR-Ⅰ,Smad2/3,IFN-γ treatment group exerted its anti-fibrosis effect.