衣康酸对大鼠部分肝切除术后肝再生及炎症反应的影响

doi:10.12160/j.issn.1672-5190.2025.03.001

摘要/Abstract

摘要： [目的]探究4-辛基衣康酸（4-OI）对大鼠部分肝切除术后肝再生及炎症反应的影响。[方法]将30只健康的雄性SD大鼠随机分为假手术组、模型组和3个不同剂量的4-OI干预组（低、中、高剂量）。假手术组大鼠仅开腹翻动肝叶,模型组建立70%肝切除模型,4-OI低、中、高剂量组建立70%肝切除模型,并在术前连续3 d、术后即刻和术后1 d继续腹腔注射4-OI,各组剂量分别为1、3、6 mg/（kg·d）。采集各组大鼠肝脏组织进行称重,计算肝再生率,HE染色并观察肝脏组织形态学的变化,免疫组织化学染色法检测Ki-67和增殖细胞核抗原（PCNA）表达情况,采用实时荧光定量PCR检测各组肝组织中肝细胞生长因子（HGF）、血管内皮生长因子（VEGF）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）的mRNA表达水平。[结果]与假手术组相比,模型组肝脏组织病理学损伤程度明显加重,HGF、VEGF、TNF-α、IL-1β、IL-6的mRNA的表达水平极显著（P<0.01）升高,IL-10的mRNA表达水平极显著（P<0.01）降低。Ki-67阳性细胞的平均光密度值极显著（P<0.01）升高,PCNA阳性细胞的平均光密度值升高,但无显著（P>0.05）差异。与模型组相比,4-OI干预后低剂量组HGF和VEGF的mRNA的表达水平极显著（P<0.01）升高,Ki-67和PCNA阳性细胞的平均光密度值极显著（P<0.01）升高。4-OI显著（0.01<P<0.05）降低TNF-α、IL-1β和IL-6的mRNA的表达水平,显著（0.01<P<0.05）升高IL-10的mRNA的表达水平。[结论]4-OI通过促进残余肝脏再生、抑制炎症反应,进而对大鼠部分肝切除损伤发挥保护作用。

关键词: 衣康酸, 肝损伤, 肝切除, 肝再生, 炎症反应

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

中图分类号:

R575
S857.1

李明轩, 孙雪妍, 孙靖博, 胡魁, 张加力, 刘菲, 王威, 王龙涛, 张千振. 衣康酸对大鼠部分肝切除术后肝再生及炎症反应的影响[J]. 畜牧与饲料科学, 2025, 46(3): 1-8.

LI Mingxuan, SUN Xueyan, SUN Jingbo, HU Kui, ZHANG Jiali, LIU Fei, WANG Wei, WANG Longtao, ZHANG Qianzhen. Effects of Itaconic Acid on Liver Regeneration and Inflammatory Response in Rats after Partial Hepatectomy[J]. Animal Husbandry and Feed Science, 2025, 46(3): 1-8.

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