美洲大蠊提取物黏糖氨酸对肝纤维化模型大鼠的影响及机制

Effects and mechanisms of Periplaneta americana extract sticky sugar amino acid on a rat model of hepatic fibrosis

背景:慢性肝病肝纤维化是可逆转的。有研究表明,美洲大蠊提取物具有一定的抗纤维化作用,其对实验性肝纤维化大鼠起保护作用。目的:观察美洲大蠊提取物黏糖氨酸治疗大鼠肝纤维化效果,初步探讨黏糖氨酸抗肝纤维化的作用机制。方法:采用猪血清诱导免疫性肝纤维化模型大鼠,同时采用0.5,0.25,0.10 g/kg的黏糖氨酸灌胃治疗,放射免疫法检测肝纤4项;免疫组织化学检测肝组织转化生长因子β1、组织金属蛋白酶抑制物蛋白表达强度和阳性细胞率;检测不同浓度的黏糖氨酸与转化生长因子β1、组织金属蛋白酶抑制物相关性。结果与结论:(1)美洲大蠊提取物黏糖氨酸能降低层粘连蛋白、Ⅲ型前胶原、Ⅳ型胶原和透明质酸酶水平(P<0.01),降低转化生长因子β1和组织金属蛋白酶抑制物1在肝组织的表达(P<0.01);(2)黏糖氨酸浓度与转化生长因子β1和组织金属蛋白酶抑制物1的蛋白表达呈明显的负相关(|r|>0.9);(3)结果证实,美洲大蠊提取物黏糖氨酸可逆转肝纤维化的改变,其作用机制与黏糖氨酸抑制转化生长因子β1和组织金属蛋白酶抑制物1的表达有关。

BACKGROUND： Hepatic fibrosis in chronic liver disease can be reversed. Studies have shown that Periplaneta americana extract has anti-fibrosis effect, and has protective effect on the experimental hepatic fibrosis rats. OBJECTIVE： To observe the effect of Periplaneta americana extract sticky sugar amino acid on hepatic fibrosis, and to primarily explore the mechanism of sticky sugar amino acid against hepatic fibrosis. METHODS： Rat models of immune hepatic fibrosis were induced by pig serum and intragastrically administered 0.5, 0.25, 0.10 g/kg sticky sugar amino acid. Four indexes of hepatic fibrosis were detected by radioimmunoassay. Immunohistochemical staining was used to measure transforming growth factor beta 1, tissue inhibitor of metalloproteinase protein expression intensity and positive cell rate, to determine the correlation of different concentrations of sticky sugar amino acid, transformation growth factor beta 1 and tissue inhibitor of metalloproteinase. RESULTS AND CONCLUSION：（1） The Periplaneta americana extract sticky sugar amino acid reduced the levels of laminin, type III procollagen, type IV collagen and hyaluronidase（P〈0.01） and reduced the expression of transformation growth factor beta 1 and tissue inhibitor of metalloproteinase 1 in liver tissue（P〈0.01）.（2） Sticky sugar amino acid concentration and transformation growth factor beta 1 and tissue inhibitor of metalloproteinase 1 protein expression showed a significant negative correlation（｜ r ｜ 0.9）.（3） Results confirmed that the Periplaneta americana extract sticky sugar amino acid can change the reversal of hepatic fibrosis. Its mechanism of action is associated with expression of transforming growth factor beta 1 and tissue inhibitor of metalloproteinase 1 inhibited by sticky sugar amino acids.