| [Background and Aims] Drug-induced liver injury has been the most common reason for acute liver failure and acetaminophen has been one of the main drugs to induce liver injury. Stem cell transplantation is the most promising method to the treatment of acute liver injury. In our experinment, the model of acetaminophen induced acute liver injury was established. Human mesochymal stem cells(hMSCs) were then transplanted via caudal vein, spleen and portal vein to this model .The results of liver function and pathologic recovery before and after transplantation of hMSCs were evaluated, the effects of different methods were compared. The feasibility of hepatic functional recovery and structural regeneration were studied The screening and identification of differential expression proteins were also studied to detect the hepatic tissue proteins associated with acute liver injury by acetaminophen thus apply the possible target for treatment. [Methods] Model of acetaminophen induced acute liver injury was established by acetaminophen intragastric administration via gastric tube with the quantity of 500mg/kg. 60 severe combined immune deficient mouse(SCID mouse) were divided into 3 groups randomized. 1×10~6 hMSCs were transplanted via caudal vein, spleen and portal vein respectively. Liver function investigation, fluorescein staining; fluorescence microscopy and reticular fiber staining were applied to observe the biochemical and pathological changes of the mouse before and after the transplantation of hMSCs. Another 12 mouse were divided into 3 groups randomized : 2 groups with liver injury and 1group as control. Liver tissue were taken on d0, d2 and d5 after sacrificed. The protein was extracted from the specimen and run on the two-dimensional gel electrophoresis. The obvious differential protein spots were differentiated. Mass spectrometry was performedwith the spots which were significantly different and easily isolated with others, and search for the functions of the identified proteins on the special websites. [Results] Liver function of SCID mouse has been improved in certain degree, therewere significant differences between transplantation via spleen or portal vein groups and controls (P<0.05 ) . The observation of fluorescence microscopy indicated the improvement in hepatic pathology, through the hMSCs field planting, differentiating and generating, obviously in groups via spleen and portal vein and especially in the group of via portal vein. After transplantation ,the hMSCs appeared in the district of periportal vein at first and then extent to the central vein, the results of reticular fiber staining indicated that hMSCs could repair the construction of the hepatic acinus, no dominant fibrosis and pseudolobular were found. Two-dimensional gel electrophoresis and mass spectrometry found 7 protein spots which up-regulated or down-regulated most obviously were chosen to be performed mass spectrometry analysis, and 3 of them were identified. They were β — actin variant, biliverdin reductase B and aldob. β — actin variant, biliverdin reductase B were absent and aldob was absent on 62, re-expressing on d5.[Conclusions] ①hMSCs transplantation to SCID mouse was a suitable method; ②Three methods were all effective to the recovery of liver function , via portal vein and spleen had better results of liver function improvment; ③Of the three transplantational methods, better hMSCs growth in liver and acinus reconstruction were found via spleen, and best via portal vein; ④It was the best method via portal vein transplantation, both improvement of liver function and pathology. hMCS transplantation through portal vein has the best prospect in clinic. ⑤ The expression depletion of β-actin variant. biliverdin reductase B and aldob indicated that they may have been some important role for drug induced liver injury.
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