Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/ HMGB-1/ NF-κB pathway
Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/ HMGB-1/ NF-κB pathway
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DOI：
10.1016/j.biopha.2020.109967
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发表时间：
2020-05-01
影响因子：
7.5
通讯作者：
Silici, Sibel
中科院分区：
文献类型：
--
作者：
Doganyigit, Zuleyha;Okan, Asli;Silici, Sibel
感染引起的脓毒症是临床医学的重要问题之一。本研究旨在探讨蜂产品阿匹拉尼尔（API）对脂多糖（LPS）诱导的肝损伤的影响。本研究将64只成年Sprague-Dawley大鼠分为8组：对照组、0.2、0.4和0.8 g / kg阿匹拉尼尔（API）治疗组、LPS（30 mg / kg）组、LPS + 0.2、LPS + 0.4和LPS + 0.8 g / kg API。在从大鼠获得的组织中，组织病理学评价，通过ELISA进行生化分析（过氧化氢酶-CAT、丙二醛-MDA、超氧化物歧化酶-SOD、黄嘌呤氧化酶-XOD和睾丸素1-TCN-1），免疫组织化学评价Toll样受体4（TLR 4）、高迁移率族蛋白1（HMGB-1）、核因子κ B（NF-κ B）、肿瘤坏死因子-α（TNF-α）、白细胞介素1 β（IL-1 β）、白细胞介素6（IL-6）和诱导型一氧化氮（iNOS）），进行TUNEL分析以确定凋亡细胞的数量，并进行彗星试验作为DNA损伤的指标。组织学检查显示LPS组肝组织血管扩张、炎性细胞浸润、细胞核固缩、肝细胞受损。发现与LPS组相比，LPS + API处理组中的组织损伤显著降低。与对照组和仅API处理组相比，在LPS组中观察到的肝样品中TUNEL阳性细胞的数量增加（p < 0.05）。在用LPS + API处理的组中，与LPS组相比，TUNEL阳性细胞的数量显示出统计学上显著的减少。LPS处理增加了MDA、XOD和TCN 1水平，降低了SOD和CAT水平; LPS + API处理组逆转了这种作用。与LPS + API相比，LPS组DNA损伤明显增加。LPS处理可增加TLR 4、HMGB-1、NF-κ B B、iNOS、TNF-α、IL-1 β、IL-6的表达; LPS + API处理组可降低这种增加。总之，认为大鼠给予阿匹拉尼尔可通过抑制TLR 4/ HMGB-1 /NF-κ B信号通路来预防LPS诱导的肝损伤。
Sepsis caused by infection is one of the most important problems of clinical medicine. This study aimed to determine the effect of Apilarnil (API), a bee product, on lipopolysaccharide (LPS) induced liver injury. In the study, 64 adult Sprague-Dawley rats were divided into eight groups; control, 0.2, 0.4 and 0.8 g / kg apilarnil (API) treated groups, LPS (30 mg / kg) group, LPS + 0.2, LPS + 0.4 and LPS + 0.8 g / kg API. At tissues obtained from rats, histopathological evaluation, biochemical analysis by ELISA (Catalase-CAT, malondialdehyde-MDA, superoxide dismutase-SOD, xanthine oxidase-XOD, and testican 1-TCN-1), immunohistochemical evaluation (Toll-like receptor 4 (TLR4), High Mobility Group Box Protein 1 (HMGB-1), nuclear factor kappa B (NF-kappa B), Tumor necrosis factor-alpha (TNF-alpha), Interleukin 1 beta (IL-1 beta), Interleukin 6 (IL-6) and Inducible nitric oxide (iNOS)), TUNEL analysis to determine the number of apoptotic cells and Comet test as an indicator of DNA damage were performed. Histopathological examination revealed dilated blood vessels, inflammatory cell infiltration, and pyknotic nuclei damaged hepatocytes in the liver tissues of the LPS group. It was found that tissue damage was decreased significantly in LPS + API treatment groups compared to the LPS group. The number of TUNEL positive cells observed in the LPS group in liver samples increased compared to control and API-treated groups only (p < 0.05). The number of TUNEL positive cells showed a statistically significant decrease compared to the LPS group in the groups treated with LPS + API. LPS treatment increased MDA, XOD, and TCN 1 levels and decreased SOD and CAT levels; this effect was reversed in the groups treated with LPS + API. In the LPS group, DNA damage was significantly increased when compared with the LPS + API. LPS treatment increased expression of TLR4, HMGB-1, NF-kappa B, iNOS, TNF-alpha, IL-1 beta, IL-6; in the groups treated with LPS + API reduced this increase. In conclusion, apilarnil administered in rats may be thought to prevent LPS-induced liver damage by inhibiting the TLR4 / HMGB-1 / NF-kappa B signaling pathway.