This study aims to investigate the protective effect of miR-214 against acute liver injury induced by sepsis. An acute liver injury model in septic mice was established using the CLP method. The mice were randomly assigned to four groups: the sham operation group (sam), the model group (model), the miR-214 inhibitor group (inhibitor), and the miR-214 mimic group (mimic). Liver function indices, including ALT and AST, as well as inflammatory factors such as IL-6, IL-11, IL-1β, and TNF-α, were measured across all groups. Liver histopathological damage was evaluated microscopically following hematoxylin-eosin staining, and the pathological sections were scored accordingly. Additionally, the protein levels of TLR4, NF-κBp65, p-NF-κBp65, and IκB-α in liver tissues were assessed using protein blotting. The expression levels of miR-214 in the liver tissues of mice from each group were quantified by RT-qPCR. The administration of miR-214 mimics resulted in a reduction in ALT and AST levels, indicating improved liver function. Furthermore, miR-214 mimics inhibited the levels of inflammatory factors, including IL-6, IL-11, IL-1β, and TNF-α. Additionally, there was a decrease in the protein expression of TLR4, NF-κBp65, p-NF-κBp65, and IκB-α in septic mice. These effects collectively mitigated liver tissue damage and facilitated the recovery of hepatic histopathological injury.Our findings suggest that the overexpression of miR-214 may confer a protective effect against acute liver injury in a mouse model of sepsis.
1. In comparison to the sham operation group, serum levels of ALT and AST were significantly elevated in both the model and miR-214 inhibitor groups (P<0.001). Additionally, when comparing the model group to the miR-214 inhibitor group, serum levels of ALT and AST were notably lower in the miR-214 inhibitor group (P<0.001). These experimental findings suggest that miR-214 contributes to the recovery of liver function in mice experiencing acute liver injury due to sepsis (see Table 1 and Figure 1).
2. Compared to the sham operation group, serum levels of inflammatory factors (TNF-α, IL-6, IL-11, IL-1β) were significantly elevated in both the model and miR-214 inhibitor groups (P<0.001). Furthermore, when comparing the model group to the miR-214 mimics group, the serum levels of inflammatory factors (TNF-α, IL-6, IL-11, IL-1β) were significantly higher in the miR-214 mimics group, while these levels were significantly reduced in the miR-214 mimics group compared to the model group (P<0.001). These experimental results suggest that miR-214 plays a role in mitigating the inflammatory response in vivo in mice with acute liver injury resulting from sepsis (see Table 2 and Figure 2).
3. Compared to the sham operation group, the pathological scores of hepatic tissue injury were markedly higher in both the model and miR-214 inhibitor groups (P<0.001). Furthermore, when compared to the model group, the pathological scores of hepatic tissue injury in the miR-214 inhibitor group were significantly elevated, while the miR-214 mimics group exhibited significantly lower liver tissue injury pathology scores than the miR-214 inhibitor group (P<0.001). These experimental results suggest that miR-214 mimics may facilitate the recovery of liver tissue injury in mice experiencing acute liver injury due to sepsis (see Table 3 and Figure 3).
4. Hepatic tissue TLR4 pathway protein expression in mice exhibited significant differences among the various groups. Compared to the sham operation group, the protein expression levels of TLR4, NF-κBp65, p-NF-κBp65, and IκB-α were markedly increased in both the model group and the miR-214 inhibitor group (P<0.001). Additionally, when compared to the model group, the hepatic tissue expression of TLR4, NF-κBp65, p-NF-κBp65, and IκB-α was significantly elevated in the miR-214 inhibitor group. In contrast, the expression levels of these proteins significantly decreased in the miR-214 mimics group (P<0.001). The experimental results suggest that miR-214 mimics inhibit the expression of proteins associated with the TLR4 signaling pathway (see Figure 4a and 4b).
5. In comparison to the sham operation group, the expression of miR-214 in the liver tissue of mice in both the model and miR-214 inhibitor groups was significantly decreased. Both groups exhibited more severe symptoms of sepsis and greater liver tissue injury (P<0.001). Furthermore, when compared to the model group, the miR-214 inhibitor group showed a significant reduction in miR-214 expression in liver tissue, which correlated with an improvement in sepsis symptoms and liver tissue injury. Conversely, in the miR-214 mimics group, the expression of miR-214 in liver tissue increased significantly, leading to exacerbated sepsis symptoms and liver tissue injury (P<0.001). These experimental results suggest that overexpression of miR-214 plays a protective role against acute liver injury in the context of sepsis (see Table 4 and Figure 5).
6. Using bivariate Pearson's test, miR-214 exhibited a negative correlation with the severity of acute liver injury in sepsis (P<0.01). Therefore, supplementation with miR-214 seems to promote recovery from acute liver injury in sepsis (see Figure 6).
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