鲨肝活性肽对对乙酰氨基酚致小鼠急性肝损伤的保护作用

Protective effects of shark hepatic stimulator substance against acute hepatic injury induced by acetaminophen in mice

目的 探讨鲨肝活性肽 (sHSS)对对乙酰氨基酚 (AAP)致小鼠急性肝损伤的保护作用。方法 用AAP( 2 0 0mg·kg- 1 ,ip)诱导小鼠急性肝损伤 ,用改良赖氏法测血清ALT和AST ,通过光镜和电镜观察肝细胞显微和亚显微结构的变化 ,用流式细胞仪分析肝细胞凋亡 ,同时用RT PCR方法分析FasmRNA表达水平。结果 sHSS 3 0和 1 5mg·kg- 1 可显著降低肝损伤小鼠血清ALT和AST的水平 ;改善模型鼠肝组织细胞坏死及炎症反应 ;高剂量sHSS( 3mg·kg- 1 )对肝线粒体具有保护作用 ,下调FasmRNA的表达水平 ,并具有抗凋亡作用。结论 sHSS对AAP诱导的肝损伤具有明显的保护作用 ,其机制可能与保护肝线粒体、抑制Fas基因表达及肝细胞凋亡有关。

Aim To investigate the protective effects of shark hepatic stimulator substance (sHSS) against acute hepatic injury induced by acetaminophen (AAP) in mice. Methods Acute hepatic injury model of Balb/c mice was induced by a single intraperitoneal injection of AAP (200 mg·kg -1, ip). Serum ALT and AST activities were analyzed. The changes of microstructure and ultrastructure of hepatocyte were observed under optical and electronic microscope. The hepatocyte apoptosis was analyzed by flow cytometer and the expression level of Fas mRNA was determined by RT PCR. Results The activities of serum ALT and AST were significantly decreased and both necrosis and inflammatory infiltration were improved in the mice treated with sHSS 3 0 and 1 5 mg·kg -1 . sHSS (3 0 mg·kg -1 ) prevented the ultrastructural changes of hepatocytes caused by AAP, decreased the percentage of apoptotic cells, and downregulated the expression level of Fas mRNA. Conclusion sHSS protected hepatocytes from AAP induced injury, which might be associated with its protection of the mitochondria and inhibition of apoptosis and expression of Fas mRNA in hepatocytes.