Altan Mehmet, Yaman Muhittin Onur, Kervancıoğlu Gülnaz, Kılıç Aysu, Demirci Elif Kervancıoğlu, Bozdoğan Polat Sıla Hidayet, Karadeniz Zeliha, Güner Ibrahim, Yelmen Nermin, Şahin Gülderen
Istanbul University-Cerrahpaşa, Cerrahpasa Medical Faculty, Department of Physiology, Istanbul, Turkey.
Istanbul University-Cerrahpaşa, Vocational School of Health Sciences, Istanbul, Turkey.
Iran J Basic Med Sci. 2023 Mar;26(3):301-307. doi: 10.22038/IJBMS.2023.65974.14508.
Due to cross-clamping of the aorta during aortic aneurysm surgeries, ischemia-reperfusion (IR) develops, and it may cause damage to the aorta itself or even to remote organs by oxidative stress or inflammation. Fluoxetine (FLX) which might be used in the preoperative period for its tranquilizing effect also has antioxidant effects in short-term use. The purpose of our study is to examine whether FLX protects aorta tissue, against the damage caused by IR.
Three groups of Wistar rats were formed randomly. 1) Control group (sham-operated), 2) IR group (60 min ischemia+120 min perfusion), and 3) FLX+IR group (FLX dose was 20 mg/kg for 3 days IP before IR). At the end of each procedure, aorta samples were collected, and oxidant-antioxidant, anti-inflammatory, and anti-apoptotic status of the aorta were evaluated. Histological examinations of the samples were provided.
Levels of LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA were found to be significantly increased in the IR group compared with control (<0.05) and SOD, GSH, TAS, and IL-10 levels were significantly lower (<0.05). FLX significantly decreased LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA levels in the FLX+IR group compared with IR group (<0.05) and increased IL-10, SOD, GSH, and TAS (<0.05). FLX administration prevented the deterioration of aortic tissue damage.
Our study is the first study that demonstrates FLX-mediated suppression of IR injury in the infrarenal abdominal aorta by antioxidant, anti-inflammatory, and anti-apoptotic properties.
在主动脉瘤手术期间,由于主动脉的交叉钳夹,会发生缺血再灌注(IR),这可能通过氧化应激或炎症对主动脉本身甚至远处器官造成损害。氟西汀(FLX)因其镇静作用可能在术前使用,短期使用时也具有抗氧化作用。我们研究的目的是检查FLX是否能保护主动脉组织免受IR引起的损伤。
将Wistar大鼠随机分为三组。1)对照组(假手术组),2)IR组(60分钟缺血 + 120分钟灌注),3)FLX + IR组(在IR前3天腹腔注射FLX,剂量为20mg/kg)。在每个手术结束时,收集主动脉样本,并评估主动脉的氧化 - 抗氧化、抗炎和抗凋亡状态。对样本进行组织学检查。
与对照组相比,IR组中丙二醛(MDA)、活性氧(ROS)、总氧化应激(TOS)、髓过氧化物酶(MPO)、肿瘤坏死因子α(TNFα)、白细胞介素 - 1β(IL - 1β)、白细胞介素 - 6(IL - 6)、核因子κB(NF - kB)、基质金属蛋白酶 - 9(MMP - 9)、半胱天冬酶 - 9(caspase - 9)、8 - 羟基脱氧鸟苷(8 - OHdG)、一氧化氮(NO)和透明质酸(HA)水平显著升高(<0.05),而超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、总抗氧化能力(TAS)和白细胞介素 - 10水平显著降低(<0.05)。与IR组相比,FLX + IR组中FLX显著降低了丙二醛(MDA)、活性氧(ROS)、总氧化应激(TOS)、髓过氧化物酶(MPO)、肿瘤坏死因子α(TNFα)、白细胞介素 - 1β(IL - 1β)、白细胞介素 - 6(IL - 6)、核因子κB(NF - kB)、基质金属蛋白酶 - 9(MMP - 9)、半胱天冬酶 - 9(caspase - 9)、8 - 羟基脱氧鸟苷(8 - OHdG)、一氧化氮(NO)和透明质酸(HA)水平(<0.05),并提高了白细胞介素 - 10、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和总抗氧化能力(TAS)(<0.05)。FLX给药可防止主动脉组织损伤的恶化。
我们的研究是第一项证明FLX通过抗氧化、抗炎和抗凋亡特性介导抑制肾下腹主动脉IR损伤的研究。