Protective effect of adipose-derived mesenchymal stem cells on liver injury in rats with heat stroke

  Objective  To explore the protective effect of adipose derived mesenchymal stem cells (MSCs) on liver injury in rats with heat stroke.

  Methods  MSCs were isolated from 5 immature SD rats and subcultured to P4. Thirty SD rats were randomly divided into three groups: control group (n=6), model(HS) group (n=12) and MSCs (HS+MSCs) treatment group (n=12). The control group was reared in room temperature of 25℃ and humidity of 40%; the HS group and HS+MSCs group were placed in biochemical incubator at 40℃ and 45% humidity respectively, and the rectal temperature was continuously monitored until the core temperature reached 42℃, as the rats showed limb motor dysfunction, it suggested that the HS rat model was successfully constructed. Then the rats were removed and placed at room temperature. MSCs (2×10⁶) suspended in 0.3 mL 0.9% sodium chloride solution (NS) were injected into the caudal vein of rats in the HS+MSCs group, and 0.3 mL NS was injected into the caudal vein of rats in the HS group. The liver samples were taken and fixed at different time points (3 d, 14 d). HE staining was used to observe the pathological changes of liver, and Luminex platform was used to detect the levels of six inflammatory factors in rats' liver tissues.

  Results  After the core temperature reached 42℃, the rat model was established successfully. HE staining results of the rat liver showed inflammatory cell infiltration, disordered arrangement of hepatocytes, spotty and patchy hemorrhage, balloon like degeneration, etc. The pathological changes of liver tissue in the HS rats treated with MSCs were milder than those in the HS rats. In terms of pro-inflammatory factors, the levels of IL-1 β, IL-6 and TNF - α in liver tissue of the HS group were significantly higher than those of the control group (P＜0.05). Only IL-1 β of the HS MSCs rats was higher than that of the control group (P＜0.05), while the levels of IL-1 β, IL-6 and TNF - α were mostly lower than those of the HS group at each time point (P＜0.05). For anti-inflammatory factors, the levels of IL-10 and IL-13 in the HS group were higher than those in the HS MSCs group (P＜0.05), and those in both of the above two groups were significantly higher compared to the control group (P＜0.05) at day 3 (P＜0.05), but there was no significant difference between them the three groups at day 14 (P＞0.05); There was no significant difference in IL-4 between the three groups (P＞0.05).

  Conclusion  HS rats treated with MSCs have lower level of pro-inflammatory factors and higher level of anti-inflammatory factors compared to the HS rats, which indicates that MSCs have a definitely protective effect on the liver of HS rats.