Moradi Mojtaba, Farbood Yaghoob, Mard Seyyed Ali, Dianat Mahin, Goudarzi Gholamreza, Khorsandi Layasadat, Seyedian Seyed Saeed
Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Alimentary Tract Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Iran J Basic Med Sci. 2023 Feb;26(2):164-175. doi: 10.22038/IJBMS.2022.66192.14554.
Studies show that chronic injuries like air pollution or acute damage such as hepatic ischemia-reperfusion (IR) cause various cellular pathologies such as oxidative stress, apoptosis, autophagy, and inflammation in hepatocytes. -Coumaric acid (CA) is known as an antioxidant with many therapeutic impacts on inflammatory-related pathologies. In this experiment, we aimed to assess the hepatoprotective effects of -CA on liver damage induced by dust and IR injury in adult male rats.
Forty-eight adult male Wistar rats were divided into 6 groups; Control (CTRL); sham; DMSO+Dust+Laparotomy (LPT); DMSO+Dust+Ischemia-reperfusion (IR); -CA+Dust+LPT; and -CA+Dust+IR. Clean air, DMSO, -CA, and dust were administrated 3 days a week for 6 consecutive weeks. Animals were sacrificed, the blood samples were aspirated and the liver sections were prepared for biochemical and histopathological assessments.
Significantly (<0.05), the results represented that dust and IR can potentially increase the levels of ALT, AST, direct and total bilirubin, triglyceride, and cholesterol in serum. Also, MDA, TNF-α , NF-κB . HMGB-1 and ATG-7 levels were increased in hepatocytes. Gene expression of Nrf2, HOX-1, IL-6, HOTAIR, and miR-34a showed an incremental trend in the liver tissue. Total antioxidant capacity (TAC) in hepatocytes was decreased following dust exposure and IR induction. Also, miR-20b-5p, MEG3, and SIRT1 in the liver were decreased in dust and dust+IR groups.
-CA alleviated pathological changes caused by dust exposure and IR injury. -CA protected hepatic injury induced by dust and IR by inhibition of oxidative injury, inflammation, and autophagy.
研究表明,空气污染等慢性损伤或肝缺血再灌注(IR)等急性损伤会导致肝细胞出现各种细胞病变,如氧化应激、细胞凋亡、自噬和炎症。对香豆酸(CA)是一种抗氧化剂,对炎症相关病症具有多种治疗作用。在本实验中,我们旨在评估对香豆酸对成年雄性大鼠粉尘和IR损伤诱导的肝损伤的肝保护作用。
48只成年雄性Wistar大鼠分为6组;对照组(CTRL);假手术组;二甲基亚砜+粉尘+剖腹术(LPT)组;二甲基亚砜+粉尘+缺血再灌注(IR)组;对香豆酸+粉尘+LPT组;对香豆酸+粉尘+IR组。每周3天连续6周给予清洁空气、二甲基亚砜、对香豆酸和粉尘。处死动物,抽取血样,并制备肝组织切片进行生化和组织病理学评估。
结果显示(P<0.05),粉尘和IR可显著升高血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、直接胆红素和总胆红素、甘油三酯和胆固醇水平。此外,肝细胞中丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、高迁移率族蛋白B1(HMGB-1)和自噬相关蛋白7(ATG-7)水平升高。肝组织中核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HOX-1)、白细胞介素-6(IL-6)、HOX转录反义RNA(HOTAIR)和微小RNA-34a(miR-34a)的基因表达呈上升趋势。粉尘暴露和IR诱导后,肝细胞中的总抗氧化能力(TAC)降低。此外,粉尘组和粉尘+IR组肝脏中的微小RNA-20b-5p、母系表达基因3(MEG3)和沉默信息调节因子1(SIRT1)降低。
对香豆酸减轻了粉尘暴露和IR损伤引起的病理变化。对香豆酸通过抑制氧化损伤、炎症和自噬保护粉尘和IR诱导的肝损伤。