| 董毅玲,张文文,闫琰,等.全反式维甲酸抑制核因子 E2相关因子 2和血红素加氧酶 1加重大鼠肾脏缺血再灌注损伤表达[J].安徽医药,2024,28(4):741-745. |
| 全反式维甲酸抑制核因子 E2相关因子 2和血红素加氧酶 1加重大鼠肾脏缺血再灌注损伤表达 |
| ATRA inhibits Nrf2 and HO-1 expression to aggravate the renal ischemia-reperfusion injury in rats |
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| DOI：10.3969/j.issn.1009-6469.2024.04.022 |
| 中文关键词: 急性肾损伤 再灌注损伤 核因子 E2相关因子 2 血红素加氧酶 1 全反式维甲酸 |
| 英文关键词: Acute kidney injury Reperfusion injury Nuclear factor erythroid-2 related factor 2 (Nrf2) Heme oxygenase1 (HO-1) All-trans retinoic acid (ATRA) |
| 基金项目:山西省 “136”兴医工程专项基金( SZ2019011) |
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| 中文摘要: |
| 目的观察用全反式维甲酸( all-trans retinoic acid，ATRA)抑制核因子 E2相关因子 2(Nrf2)和血红素加氧酶 1(HO-1)是否会加重大鼠肾脏缺血再灌注损伤( IRI)表达。方法 2020年 10月至 2022年 2月选取 24只健康成年雄性 SD大鼠切除右肾，并按随机数字表法分为 3组( n=8)，即假手术组( Sham)、肾脏缺血再灌注( I/R)组、全反式维甲酸( I/R+ATRA)组。其中 Sham组和 I/R组给予腹腔注射玉米油( 1 mL·kg?1·d?1)1周， ATRA组则给予腹腔注射溶于玉米油的 ATRA(10 mg·kg?1·d?1)1周后， 3组大鼠用 10%的水合氯醛( 0.3 mL/100 g)进行麻醉后固定四肢，将其在 37 ℃条件下沿腹中线打开腹腔并分离出左肾动脉。其中 Sham组切除右肾，不予以夹闭左肾动脉； I/R组和 ATRA组采用右肾切除联合左肾动脉夹闭 45 min后再灌注 24 h的方法建立大鼠肾脏 I/R模型。实验结束后收集 3组大鼠血清及肾组织标本，用比色法检测血清肌酐(Scr)、血尿素氮(BUN)浓度； HE染色法观察肾组织病理改变； TUNEL法进行肾组织细胞凋亡的检测；二氢乙啶( DHE)荧光染色评估肾组织活性氧的表达情况；通过比色法检测肾组织丙二醛( MDA)浓度、超氧化物歧化酶( SOD)活性；用蛋白质印迹法分别对 Nrf2、HO-1的表达进行检测。结果与 Sham组相比， I/R组大鼠肾组织 Nrf2、HO-1蛋白表达量均增加( P<0.01)活性氧表达量增加， SOD活性下降， MDA含量、血清 Scr、BUN浓度升高( P<0.01)肾小管损伤评分及凋亡细胞表达较高(P<0.05)，其中 Nrf2蛋白和 HO-1蛋白分别为 0.52±0.09和 0.37±0.79，高于Sham组的0.06±，0.01和 0.02±0.01。与 I/R组相比， I/R+ATRA组大，鼠肾组织 Nrf2、HO-1蛋白显著减少( P<0.01)活性氧表达量明显增加， SOD活性严重下降， MDA含量、血清 Scr、BUN浓度明显升高( P<0.01)肾小管损伤评分显著增加，凋亡细胞表达亦增高( P<0.05)其中 I/R+ATRA组 Nrf2蛋白和 HO-1蛋白分别为 0.29±0.04.15±0.03，显著低于 I/R组。结论 Nrf2/HO-1通路参与肾脏缺灌注损伤过程， ATRA可能通过抑制 Nrf2/HO-1通路，加重氧化应激，进一步加重肾肾脏，和0，血再， |
| 英文摘要: |
| Objective To investigate whether inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression by all-trans retinoic acid (ATRA) aggravates the renal ischemia-reperfusion injury (I/R) in rats.Methods From Oc? tober 2020 to February 2022, 24 healthy adult male SD rats were selected to remove their right kidneys, and they were randomly as?signed into three groups: sham operation group (Sham), I/R group, and ATRA group, with 8 rats in each group. The rats in Sham and I/Rgroups were given intraperitoneal injection of corn oil (1 mL·kg?1·d?1) for 1 week. The rats in the ATRA group were injected intraperito? neally with ATRA dissolved in corn oil (10 mg·kg?1·d?1) for 1 week. 3 groups of rats were anesthetized with 10% chloral hydrate (0.3mL/100 g) and fixed limbs. The abdominal cavity was opened along the abdominal midline and the left renal artery was separated at37 ℃. In the Sham group, the right kidney was excised without blocking the left renal artery. Renal I/R model was established by rightnephrectomy combined with left renal artery occlusion for 45 min followed by 24 h reperfusion in I/R and ATRA groups. After the ex?periment, three groups of rats serum and kidney tissue samples were collected. The concentrations of serum creatinine (Scr) and bloodurea nitrogen (BUN) were detected by colorimetric method. HE staining was used to observe the pathological changes of kidney tissue.The apoptosis of renal tissue cells was detected by TUNEL staining. The expression level of reactive oxygen species (ROS) in renal tis?sue was evaluated by dihydroethidium (DHE) fluorescence staining. A colorimetric method was used to determine the contents of super?oxide dismutase (SOD) and malondialdehyde (MDA) in the kidney tissue. The protein expression levels of Nrf2 and HO-1 were detected by Western blotting.Results Compared with the sham group, the protein expressions of Nrf2 and HO-1 in renal tissues of rats in I/R group were significantly increased (P<0.01). The contents of ROS, MDA, Scr, BUN were increased and SOD activity was decreased (P< 0.01). Renal tubular injury score and positive rate of apoptotic cells were higher (P<0.05), among them, Nrf2 protein and HO-1 proteinwere 0.52±0.09 and 0.37±0.79, respectively, which were higher than those of Sham group 0.06±0.01 and 0.02±0.01. Compared with theI/R group, the expressions of Nrf2 and HO-1 protein in kidney tissue of ATRA group was significantly decreased (P<0.01). The con? tents of ROS, MDA, Scr and BUN were significantly increased and the SOD activity was reduced (P<0.01). The renal tubular injury score and positive rate of apoptotic cells were significantly increased (P<0.05). Among them, The protein levels of Nrf2 and HO-1 in ATRA group were 0.29±0.04 and 0.15±0.03, respectively, which were significantly lower than those in I/R group.Conclusion Nrf2/ HO-1 signaling pathway is involved in the process of renal I/R injury. ATRA may further aggravate renal I/R injury by inhibiting Nrf2/ HO-1 pathway and aggravating oxidative stress. |
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