Experimental Study On Rhubarb Extract Combined With Marrow Mesenchymal Stem Cells Transplantation In The Treatment Of Acute Liver Failure

Objective:To study the efficacy of bone marrow mesenchymal stem cells (MSCs) transplantation combined with rhubarb for acute liver failure (ALF)Methods:ALF model of rats were induced by intraperitoneal injection of D-galactosamine (D-gal)(1.5g/Kg). MSCs of rats were isolated and cultured by the combination of Density gradient centrifugation and adherence screening method, then MSCs were identified by flow cytometry. Spraggs-Bawley rats were randomly divided into five groups (n=10), and all rats were given D-gal to induce ALF. Group A received lml distilled water after D-gal induction; Group B received approximately1×106MSCs suspended in1L normal saline via the caudal vein24h after D-gal induction; Group C received gastrologically administered with small dose of Rhubarb powder dissolved in aqueous solution (0.25g/kg,10ml/kg) once a day24h after D-gal induction, MSCs transplantation was carried out24h after D-gal induction; Group D received gastrologically administered with middle dose of large dose of Rhubarb powder dissolved in aqueous solution (0.5g/kg,10ml/kg) once a day24h after D-gal induction, MSCs transplantation was carried out24h after D-gal induction; Group E received intragastrically administered with Rhubarb powder dissolved in aqueous solution (1g/kg,10ml/kg) once a day24h after D-gal induction, MSCs transplantation was carried out24h after D-gal induction. Liver function, serum inflammatory parameters, pathological changes and Survival were measured.Results:The experimental results show that D-Gal will lead to acute liver failure in rats and seriously damage liver failure, therefore the model has been successfully built up. By flow cytometry, ninety-nine percent MSCs at passage5were positive for CD90but negative for CD45. Group D can obviously prolong the survival time and lower the death rate based on the rats’survival in each group, which has the remarkable difference in statistics compared to other groups (P<0.05), while comparison between other groups has no statistical difference (P>0.05). The results of liver function test show that all the indexes of liver function of rats in Group B、C、D and E such as ALT、AS、TBiL、serum ammonia, etc have been improved significantly, which has statistical significance compared to Group A (P<0.05), what’s more, all the indexes of liver function of rats in Group D drop at the fastest rate and have the most obvious effect for improvement, which has statistical difference compared to Group B、C and E (P<0.05), while comparison between other treatment groups has no statistical difference (P0.05). The improvement of rats in Group D has significant difference compared to other groups in the aspect of the inflammatory factors (P<0.05), other treatment groups have all been improved to a certain extent but have no statistical difference compared to Group A (P>0.05) From the pathological score of liver tissue, we can know that the liver damage of rats in Group D is obviously reduced, which has significant difference compared to Group A (P<0.05), other treatment groups’liver damage are all reduced to a certain degree, but it has no significant statistical difference compared to Group A (P>0.05). The results of cell proliferation show that the cell proliferation of rats in Group B、C、D and E have obviously increased, which has significant difference compared to Group A (P<0.05), Group D has the largest number of proliferation and it has statistical difference compared to Group B、C and E (P<0.05), while there is no statistical difference between other treatment groups (P>0.05)Conclusion:Rhubarb can improve the internal environment of liver inflammation, promote cell proliferation after MSCs transplantation and enhance the effect of MSCs transplantation. Middle dose of Rhubarb combined with MSCs transplantation can more obviously improve all the indexes of the liver function of rats with ALF. Combination therapy with rhubarb and MSCs transplantation can promote the restoration and reconstruction of acute liver injury in rats, and is a promising future treatment for patients with ALF.