Abstract: Objective To investigate the protective effect of mesenchymal stem cells combined with TLR4 monoclonal antibody as the treatment of liver injury in heatstroke mice. Methods Mesenchymal stem cells were obtained from inguinal fat tissue separated from living mice. Mice were randomly divided into four groups: blank control group (control), heat stroke group (HS), stem cell intervention group (MSC), and stem cell+TLR4 antibody intervention group (MT). After the successful modeling of heat stroke in the experimental mice, 1 mL of 0.9% sodium chloride injection was injected intraperitoneally in the HS group. The MSC group was injected with 2×10⁶ MSCs. In the MT group, 2×10⁶ MSCs and 100 μg TLR4 monoclonal antibody were injected. After 7 days of refeeding, 1ml of orbital venous blood was collected, serum ALT and AST were detected by biochemical instrument, and inflammatory factors IL-1β, IL-6 and TNF-α were detected by Elisa method. At the same time, the mice were sacrificed to collect liver tissue, and the sections were fixed and stained with HE. SPSS 19.0 was used for the analysis of experimental data. Results The liver histopathology of HS group mice showed that the hepatocyte cord arrangement was disordered, the hepatocytes were moderately to severely turbid with vacuolar degeneration, some hepatocytes were necrosis, and a small amount of scattered lymphocyte infiltration. Mild to moderate turbidity of hepatocytes and moderate vacuolar structures were observed in the liver tissues of mice in the MSC group. The liver tissue damage of mice in the MT group was mild. The ALT and AST levels in the HS group mice were significantly increased, reaching 347.3 ± 130.5 U/L and 345.0 ± 229.3 U/L, respectively, with significant statistical differences compared to the other groups (P<0.01); Serum inflammatory cytokine IL-1 β, IL-6, TNF- α The levels were 185.44 ± 143.64 pg/mL, 51.42 ± 34.41 pg/mL, and 83.94 ± 54.24 pg/mL, respectively. There was a significant statistical difference compared to the other three groups, with P values of 0.003, 0.011, and 0.016, respectively. Conclusion Stem cell combined with TLR4 monoclonal antibody therapy improves liver injury in heat stroke mice through NF- κ B inflammatory signaling pathway; And the combination therapy has a synergistic effect.

Key words: Heat stroke disease, Mesenchymal stem cell, Monoclonal antibodies, Liver injury