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目的评价微载体培养的永生化人肝细胞(immortalized human hepatocytes,IHH)对裸鼠急性肝衰竭(acute liver failure,ALF)的治疗作用。方法采用腹腔注射四氯化碳(CCl4)建立裸鼠ALF模型,将微载体培养的IHH注射于裸鼠腹腔内进行腹膜透析治疗,并设未治疗组和空微载体治疗组,比较各组动物的肝功能损伤指标,肝组织病理和动物生存率。结果腹腔注射CCl4后24h,所有动物的转氨酶升高达正常值10倍以上,未治疗组和空微载体治疗组动物48h内全部死亡,肝组织检查发现肝细胞广泛坏死;而采用IHH微载体治疗组,48h的动物生存率为83.3%,持续14d后转为长期存活。存活的动物转氨酶降至正常水平,肝组织检查显示肝细胞坏死显著减少,免疫组织化学染色显示腹腔微载体上肝细胞仍存活,并表达人肝细胞特异蛋白α1-抗胰蛋白酶(α1-antitrypsin,α1-AT)。结论采用微载体培养的IHH腹腔透析治疗小鼠ALF是有效的,表明IHH适合作为生物人工肝的细胞材料。
Objective To evaluate the therapeutic effect of immortalized human hepatocytes (microcatheter cultured IHH) on acute liver failure (ALF) in nude mice. Methods The nude mice model of ALF was established by intraperitoneal injection of carbon tetrachloride (CCl4). The IHH of microcarrier culture was injected into peritoneal cavity of nude mice for peritoneal dialysis treatment. The untreated group and empty microcarrier treatment group were compared. Liver function damage index, liver histopathology and animal survival rate. Results After 24 hours of intraperitoneal injection of CCl4, the aminotransferases of all the animals were up to 10 times of the normal value. All the animals in the untreated group and the empty microcarrier group died within 48 hours. Liver cells were found to have extensive necrosis of liver cells. , 48h animal survival rate was 83.3%, lasting 14d after long-term survival. Survival of animals transaminases down to normal levels, liver tissue necrosis showed a significant reduction in immunohistochemical staining showed that peritoneal microcarriers on the liver cells are still alive and express human hepatocyte-specific protein α1-antitrypsin (α1-antitrypsin, α1-AT). CONCLUSION: The treatment of mouse ALF with IHH by microcarrier culture is effective, indicating that IHH is suitable as a bioartificial liver cell material.