| Objective:?To optimize a novel hybrid bio-artificial liver support system and evaluate its safety and effectiveness in vitro.?To construct an acute liver failure(ALF)model of Tibet mini-pigs,and then treated by a novel hybrid bio-artificial liver support system which to evaluate its safety and effectiveness.Methods:?On the basis of our previous studies,we optimized the control system,appearance and pipeline system,then constructed a novel hybrid bio-artificial liver support system which realized the integration,miniaturization and intellectualization,realized the flexible application of artificial liver pipeline,and realized three treatment modes by one set of pipelines.?Evaluate the safety of the novel hybrid bio-artificial liver support system after optimized in vitro.?Furthermore,we optimized the preparation method of the simulated liver failure serum,and used the simulated liver failure serum to evaluate the safety and effectiveness of the novel hybrid bio-artificial liver support system in vitro.?The clinical manifestations,survival time,liver and renal function,coagulation function,histopathology and immunohistochemical changes of Tibet mini-pigs were compared with different doses of D-gal(0.45 g/kg,0.40 g/kg and 0.35 g/kg)through the jugular vein catheterization.?Using the novel hybrid bio-artificial liver support system to treat the ALF model of Tibet mini-pigs.Then observe and compare the clinical performance,survival time,liver and renal function,coagulation function,histopathology and immunohistochemistry in ALF group,sham treatment group and treatment group.Results:?We successfully optimize the novel hybrid bio-artificial liver support system to achieve integration,miniaturization and intellectualization,and optimize the artificial liver pipeline;?All functions of artificial liver support system are running normally,peristaltic pump,heparin pump,insufficient blood supply sensor,blood leakage sensor,liquid level sensor,bubble sensor,temperature control system,pressure sensor monitoring and control system and weighing meter are running normally.?The method of preparing simulated liver failure serum has been optimized successfully.After the treatment of the novel hybrid bio-artificial liver support system,the indexes of simulated liver failure serum have been significantly reduced,and the machine runs steadily during the treatment without any abnormal condition.?The survival time of Tibet mini-pigs with 0.45 g/kg D-gal was 39.7±5.9 h;The survival time of Tibet mini-pigs with 0.40 g/kg D-gal was longer than that of 0.45 g/kg group,which is 53 ±12.5 h;The Tibet mini-pig with 0.35 g/kg D-gal survived the longest time,and the survival time was 61.3±8.1 h,which had a longer treatment window and meet the criterion of ideal ALF model.After infusion of D-gal,the biochemical indexes of Tibet mini-pigs increased gradually.The higher the D-gal dosage,the earlier the biochemical index reached the peak value.?The biochemical indexes of the ALF model pigs in the treatment group were significantly decreased,and the survival time was significantly prolonged after the treatment of the novel hybrid bio-artificial liver support system,when compared with the ALF group and the sham treatment group.Pathological results showed that the injury of hepatocytes in the treatment group was alleviated and the regeneration of hepatocytes was obvious.Conclusions:?We have successfully optimized the novel hybrid bio-artificial liver support system,and verifiedcits safety and effectiveness in vitro by simulating liver failure serum.?We successfully constructed the Tibet mini-pigs ALF model and used it to verify the safety and effectiveness of the novel hybrid bio-artificial liver support system in vivo. |
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