鳖甲寡肽I-C-F-6对四氯化碳诱导大鼠肝纤维化的影响

摘要

目的：观察鳖甲寡肽 I-C-F-6对四氯化碳(CCl4)诱导的大鼠肝纤维化的影响,探讨其抗纤维化作用及可能机制。方法将48只SD雄性大鼠随机分为正常组、模型组、联苯双酯组和鳖甲寡肽组。每组12只,CCl4腹腔注射建立大鼠肝纤维化模型。鳖甲寡肽组、联苯双酯组按0.12μg/g体质量皮下注射给药,正常组、模型组给予等量生理盐水,连续7周。检测血清或肝组织中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的水平及丙二醛(MDA)、超氧化物歧化酶(SOD)、白细胞介素(IL)-4、IL-10、肿瘤坏死因子-α(TNF-α)的含量；苏木素-伊红(HE)染色光镜下观察组织形态学变化及免疫组化染色观察肝组织中转化生长因子-β1(TGF-β1)表达。结果与模型组比较,鳖甲寡肽组血清ALT、AST水平显著降低,肝组织MDA、TNF-α含量下降,IL-4、IL-10含量升高,SOD 活性增强,肝组织纤维化程度明显改善,TGF-β1抗体呈弱阳性表达。结论鳖甲寡肽 I-C-F-6能减轻模型大鼠肝细胞损伤,具有抗氧化和抗纤维化作用。%Objective To study effects of oligo-peptide I-C-F-6 in carapax trionycis on rats with liver fibrosis induced by CCl4;To discuss its anti-liver fibrosis effects and possible mechanisms. Methods Forty-eight SD male rats were randomly divided into normal control group, model group, bifendate group, and oligo-peptide I-C-F-6 group, 12 in each group.CCl4 was injected intraperitoneally to build rat liver fibrosis model.Oligo-peptide I-C-F-6 group and bifendate group were given subcutaneous injection of oligo-peptide I-C-F-6 (0.12μg/g) or bifendate (0.12μg/g). At the same time, normal control group and model group were giventhe same volume of saline for seven weeks. The levels ofALT, AST,MDA, SOD, IL-4, IL-10 and TNF-α were tested.The histomorphology changes were observed under optical microscopeby HE, and the expressions of transforming growth TGF-β1 were determined by immunohistochemistry.Results Compared with model group, serum levels of ALT and AST were reduced evidently in oligo-peptide I-C-F-6 group. Hepatic content of MDA, IL-4 and TNF-α decreased, while SOD activity and IL-10 were found significantly increased. Liver fibrosis was ameliorated significantly. Hepatic expressions of TGF-β1 were weakly positive.Conclusion Oligo-peptide I-C-F-6 can ameliorate hepatocyte damage of model rats, thus it has anti-oxidative and anti-liver fibrosis effects on liver fibrosis in rats.