摘要
目的:观察干扰素-α(interferon-alpha,IFN-α)对猪血清诱导大鼠肝纤维化的治疗作用,并探讨其机制。方法:45只雄性Wistar大鼠,完全随机分为正常组、模型组和IFN-α治疗组,每组15只。正常组予0.9%氯化钠注射液,模型组和IFN-α组予猪血清,腹腔注射、每次0.5mL/只,2次/周,共12周;IFN-α组于第9周给予每天IFN-α10×104U/只,皮下注射,治疗4周。于12周末处死所有大鼠,取肝组织行HE染色进行炎症活动度半定量评分;免疫组织化学法检测Ⅰ型胶原、Ⅲ型胶原、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达;Real-time PCR法检测金属蛋白酶组织抑制剂-1(tissue inhibitor ofmetalloproteinase-1,TIMP-1)mRNA表达。结果:模型组肝炎症活动度半定量评分高于正常组(P<0.001),IFN-α组较模型组降低37.56%(P<0.01);模型组I型、Ⅲ型胶原、α-SMA蛋白表达高于正常组(P<0.001),IFN-α组较模型组分别降低58.39%,52.63%,64.07%(P<0.001);模型组TIMP-1mRNA高于正常组(P<0.001),IFN-α组较模型组降低59.06%(P<0.01)。结论:IFN-α具有抗猪血清诱导的大鼠肝纤维化作用,其机制可能与减轻肝炎症程度,抑制肝星状细胞活化,降低大鼠肝组织Ⅰ型、Ⅲ型胶原的含量,阻止细胞外基质合成有关;另外,也与降低TIMP-1mRNA表达,减少TIMP-1对金属基质蛋白酶的抑制而促进细胞外基质的降解有关。
Objective To investigate the curative effect and explore the mechanism of interferon-α on rat liver fibrosis induced by pig serum.Methods Forty-five male Wistar rats were randomly divided into 3 groups: a normal control group,a model group,and an interferon-alpha(IFN-α) group(n=15 in each group).The rat in the normal control group received 0.5 mL physiological saline(introperitoneally) twice a week for 12 weeks.The rats in the model group or the IFN-α group received 0.5 mL pig serum(introperitoneally) twice a week for 12 weeks.For the IFN-α group,from the 9th week,the rats received additional IFN-α treatment at a dose of 100 000 units subcutaneously once a day.All rats were killed at the end of 12 weeks.The inflammatory activity,the protein expression of Collagen Ⅰ,Collagen Ⅲ and the α-smooth muscle actin(α-SMA) and the tissue inhibitors of metalloproteinase 1(TIMP1) mRNA were examined by semi-quantitative scoring method,immunohistochemistry and Real-time PCR,respectively.Results The semi-quantitative score for inflammatory activity in the model group was significantly higher than that in the normal group(P0.001).This increase was significantly reversed by IFN-α treatment(P0.01).The protein contents of Collagen Ⅰ and Ⅲ,α-SMA in the model group were significantly higher than those in the normal group(P0.001).These decreases were attenuated by IFN-α treatment(P0.001).The expression of TIMP1 mRNA in the model group was significantly higher than that in the normal group(P0.001),which was reduced in the IFN-α group(P0.01).Conclusion IFN-α can decrease the liver fibrogenesis induced by pig serum in rats through a mechanism involving in inhibition of the hepatic stellate cell activation and the synthesis of extracellular matrix.
出处
《国际病理科学与临床杂志》
CAS
2011年第3期193-199,共7页
Journal of International Pathology and Clinical Medicine
基金
湖南省科技厅重大课题(05sk1002-3)~~