Abstract: [Objective] To investigate the effects of 4-octylitaconic acid （4-OI） on liver regeneration and inflammatory response following partial hepatectomy in rats. [Methods] Thirty healthy male Sprague-Dawley （SD） rats were randomly allocated into five groups：a sham group, a model group, and three 4-OI intervention groups （low, medium, and high dose）. The sham group underwent laparotomy with liver lobe manipulation only, whereas the model group and the 4-OI intervention groups were subjected to a 70% hepatectomy. The 4-OI intervention groups received intraperitoneal injections of 4-OI at doses of 1, 3 and 6 mg/（kg·d）, respectively, administered for three consecutive days prior to surgery , immediately post-surgery, and on the first day after surgery. Liver tissues were harvested from each group for weighing, and the liver regeneration rate was calculated. Histological assessment was performed using hematoxylin and eosin （HE） staining to evaluate morphological changes in the liver tissue. Immunohistochemical analysis was conducted to detect the expression of Ki-67 and proliferating cell nuclear antigen （PCNA）. Additionally, real-time quantitative PCR was utilized to measure the mRNA expression levels of hepatocyte growth factor （HGF）, vascular endothelial growth factor （VEGF）, tumor necrosis factor-α （TNF-α）, inter-leukin-1β （IL-1β）, interleukin-6 （IL-6）, and interleukin-10 （IL-10） in the liver tissues. [Results] The model group exhibited significantly exacerbated histopathological damage in the liver tissue compared to the sham-operated group. The mRNA expression levels of HGF, VEGF, TNF-α, IL-1β, and IL-6 were highly significantly （P<0.01） elevated, whereas the mRNA expression level of IL-10 was highly significantly （P<0.01） reduced. The average optical density value of Ki-67-positive cells was highly significantly （P<0.01） increased, while the average optical density value of PCNA-positive cells showed a non-significant（P>0.05） increase. In contrast to the model group, the 4-OI low-dose intervention groups highly significantly （P<0.01） upregulated the mRNA expression levels of HGF and VEGF, along with highly significantly （P<0.01） elevated the average optical density values of Ki-67 and PCNA-positive cells. Furthermore, 4-OI significantly reduced the mRNA expression levels of TNF-α, IL-1β, and IL-6, while significantly increasing the mRNA expression level of IL-10 （0.01<P<0.05）. [Conclusion] 4-OI exerts a protective effect on liver resection injury in rats by promoting the regeneration of the residual liver and attenuating the inflammatory response.

Key words: itaconic acid, liver injury, liver resection, liver regeneration, inflammatory response