The Mechanism Of Protective Effects Of Bone Marrow Mesenchymal Stem Cells On Liver Injury Induced By Heat Stress In Rats

Objectives:(1)To investigate the pathogenesis of liver injury in rats with exertional heat stroke(EHS);(2)To investigate the therapeutic effects of bone marrow mesenchymal stem cells(BMSCs)on liver injury in rats with EHS.Methods:(1)The bone marrow mesenchymal stem cells(BMSCs)were isolated from the bone marrow of rats and cultured to passage 3,and the flow cytometry was used to identify the cells;(2)the EHS rat model was constructed by simulating a environment with high temperature and high humidity in which the rats were trained to exercise on four computer-controlled treadmills.16 EHSrats were infused with BMSCs at a dose of 2 x 106/ml through the caudal vein in the experimental group;while 16 EHS rats were infused with saline at a same dose through the caudal vein in the model group.Eight non-EHS rats were also infused with saline in the blank control group,.(3)Eight rats were sacrificed at day 1 and 3post-infusion,respectively.,The pathological changes of the rat liver were examined.The expressions of HMGB1 and NLRP3 were determined using semi quantitative immunohistochemistry,.ELISA was used to test the serum levels of IL-1,IL-18 and HMGB1,and 8-hydroxydeoxyguanosine in the liver.Results:(1)BMSCs from rat bone marrow were cultured to passage 3 and were identified by flow cytometry.The positive rates of CD29 and CD90 were98.4%,97.4%,and CD34 and CD45 were 0.20%,0.30%,respectively,indicating that the cultured cells were BMSCs.(2)Compared with the blank control group,the serum levels of IL-1,IL-18,HMGB1 and the expressions of NLRP3 and HMGB1 in the liver tissue of EHS rats were significantly increased(P < 0.05).Compared with the model group,the serum levels of IL-1,IL-18 and HMGB1,and theexpressions of NLRP3 and HMGB1 in the liver tissue in the BMSCs group were significantly decreased at day 1 and 3 post-infusion,and the difference between the two groups was statistically significant(P < 0.05).Compared with the BMSCs group,the pathological changes of the liver tissue in the model group were more remarkable.Conclusions: 1)Inflammatory reaction and oxidative stress are important pathogenesis of liver injury in EHS rats.2)Infusion of BMSCs through the caudal vein promotes the recovery of liver function in EHS rats.3)BMSC therapy has effects of anti-inflammation on the liver tissue,inhibition of oxidative stress,protection of the liver cells,and prevention of liver injury in EHS rats.