脂肪间充质干细胞对CCl4致犬急性肝损伤的临床疗效

Clinical therapeutic of adipose mesenchymal stem cells on acute liver injury in canines induced by carbon tetrachloride

为了研究脂肪间充质干细胞(adipose mesenchymal stem cells, ADMSCs)对四氯化碳(CCl)致犬急性肝损伤的治疗效果,探索治疗犬肝脏损伤性疾病的新药物。选取20只健康犬平均分成A、B、C、D共4组,用50%的CCl花生油溶液,按照0、0.5、1.0和1.5 mL·kg^(-1)的剂量连续7 d腹腔给药,观察临床症状,并检测生化指标,于第3天和第7天每组随机选择2只犬解剖取肝脏组织检测病理变化。用最佳造模剂量造模15只犬,分成E、F和G 3组,每组5只。E组不治疗,F组经尾静脉移植犬脂肪间充斥干细胞(adipose mesenchymal stem cells, ADMSCs)治疗,G组普通治疗,均连续治疗10 d,监测各组临床症状、生化指标并在治疗第5和第10天肝脏组织病理学对比治疗效果。结果显示:(1)造模期间:A组各项指标无明显变化;B组各项指标改变后又恢复正常;C组临床症状恶化,在1~6 d谷丙转氨酶(ALT)和谷草转氨酶(AST)的活性显著上升,肝脏组织有明显病变,无犬只死亡;D组临床症状恶化,ALT和AST活性一直显著上升,肝脏组织有明显病变,并死亡2只。(2)治疗期间:E组各项指标不断恶化,死亡4只;F组5只犬各项指标均好转,无死亡;G组临床症状、生化指标改善,组织病理学未见好转,无死亡。试验表明,连续7 d腹腔注射1 mL·kg^(-1)50%CCl花生油溶液可以建立稳定可靠的犬急性肝损伤模型,尾静脉途径移植的ADMSCs对CCl所致犬急性肝损伤有治疗效果,且比普通对症治疗效果更佳。

The aim of this study was to investigate the therapeutic effect of adipose mesenchymal stem cells(ADMSCs) on acute liver injury induced by carbon tetrachloride(CCl) in canines,and to explore a new drugs for the treatment of liver injury diseases in canines.Twenty healthy canines were randomly divided into four groups:A,B,C and D.All of canines were intraperitoneally administered with 50% carbon tetrachloride(CCl) and peanut oil solution at the dose of 0,0.5,1.0 and 1.5 mL·kg^(-1)for 7 days.Clinical symptoms and biochemical indicators were observed and determined.On day 3 and 7,2 canines in each group were randomly selected and slaughtered for detecting pathological changes of liver tissue.Then,15 canines were successfully modeled with the best modeling dose,which were divided into three groups,E,F and G,with 5 canines in each group.Canines in group E were not treated,group F were treated with adipose mesenchymal stem cells(ADMSCs) transplanted by tail vein,and group G were treated with normal treatment for 10 days.At the same time,the clinical symptoms,biochemical indexes and liver histopathology of each group were monitored and the therapeutic effects were compared on the 5th and 10th day of the treatment.The results showed that:(1) During the modeling period,the above indexes of canines in group A did not change significantly.The indexes of group B returned to normal after changes.In group C,the clinical symptoms of canines worsened,and the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) increased significantly from day 1 to day 6;the pathological changes of liver tissue were significant and no canine died.In group D,the clinical symptoms of canines worsened,the activities of ALT and AST increased significantly all the time,and there were obvious pathological changes in liver tissue,and two canines died.(2) In the treatment period:four canines in group E died due to continuous deterioration of various indicators;all indexes of 5 canines in group F were significantly improved without death.The clinical symptoms and biochemical indexes of canines in group G were improved,but the histopathology was not improved,and no death was observed.The experimental showed that intraperitoneal injection of 1 mL·kg^(-1)50% CCland peanut oil solution could establish a stable and reliable model of acute liver injury in canines.ADMSCs transplanted through tail vein had therapeutic effect on acute liver injury induced by CCl,and the therapeutic effect was better than that of conditional treatment.