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银杏叶提取物通过调节氧化应激平衡减轻大鼠造影剂诱导的急性肾损伤
毕然, 尹磊, 高巍, 于涛
青岛大学附属医院急诊内科, 青岛 266071
摘要:
[目的] 探索银杏叶提取物(EGB)减轻大鼠造影剂诱导的急性肾损伤(CI-AKI)作用效果以及可能的作用机制。[方法] 24只SD大鼠随机分为假处理组(Sham组)、银杏叶提取物组(EGB组)、模型组(CIAKI组)、银杏叶提取物治疗组(EGB+CIAKI组),采用先后经腹腔注射前列腺素合成酶抑制剂吲哚美辛(10 mg/kg)、一氧化氮合成酶抑制剂N-硝基-L-精氨酸甲酯(10 mg/kg)和碘克沙醇(10 mL/kg,约3 g碘/kg)制作CI-AKI大鼠模型,银杏叶提取物组和银杏叶提取物治疗组在造模前2 h灌胃给予银杏叶提取物,假处理组、模型组给予等量生理盐水灌胃。在造模后第24 h处死所有大鼠,采集血液样本并留取双侧肾脏标本。检测血清肌酐(SCr)、尿素氮(BUN)水平以评估肾损伤造模效果以及药物总体疗效。检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)含量评估各组大鼠氧化应激程度。HE染色法观察肾脏结构性改变,并通过半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)免疫组化染色检测大鼠肾脏凋亡蛋白表达水平。[结果] 1)与Sham组比较,CIAKI组大鼠的SCr、BUN水平显著增加(P<0.001),而EGB+CIAKI组与CIAKI组相比SCr、BUN水平显著下降(P<0.05);2)与Sham组比较,CIAKI组的T-AOC、SOD、GSH-PX、CAT活力显著降低(P<0.01),MDA含量显著升高(P<0.001),EGB+CIAKI组的SOD、GSH-PX活力较CIAKI组显著增加(P<0.05),MDA含量显著降低(P<0.01);3)与Sham组比较,CIAKI组大鼠肾损伤评分显著升高(P<0.001),而EGB+CIAKI组评分显著低于CIAKI组(P<0.001),EGB组未观察到明显的肾脏病理结构改变;4)与Sham组比较,CIAKI组大鼠Caspase-3的阳性染色细胞面积显著增加(P<0.001),EGB+CIAKI组的阳性染色细胞面积较CIAKI组显著减少(P<0.001)。[结论] EGB对CI-AKI模型大鼠有一定的肾脏保护作用,可能与调节氧化应激平衡和提高抗氧化酶活性和减轻继发的氧化应激损伤有关。
关键词:  造影剂诱导的急性肾损伤  银杏叶提取物  氧化应激
DOI:10.11656/j.issn.1672-1519.2026.09.10
分类号:R285.5
基金项目:山东省自然科学基金青年项目(ZR2020QH164)。
Ginkgo biloba extract alleviates contrast-induced acute kidney injury in rats by modulation oxidative stress homeostasis
BI Ran, YIN Lei, GAO Wei, YU Tao
Department of Emergency, The Affiliated Hospital of Qingdao University, Qingdao 266071, China
Abstract:
[Objective] To investigate the effect and potential mechanisms of Ginkgo biloba extract(EGB)on mitigating contrast-induced acute kidney injury(CI-AKI)in a rat model. [Methods] Twenty-four Sprague-Dawley(SD)rats were randomly assigned to four groups:sham group(Sham),EGB-only(EGB),CI-AKI model(CIAKI),and EGB treatment(EGB+CIAKI). The CI-AKI model was induced by sequential intraperitoneal injections of indomethacin(10 mg/kg),Nω-Nitro- L- arginine methyl ester(10 mg/kg),and iodixanol(10 mL/kg,3g I/kg). The EGB and EGB+CIAKI groups received EGB via oral gavage 2 hours prior to model induction, whereas the Sham and CIAKI groups received an equivalent volume of normal saline. All rats were euthanized 24 hours post-modeling. Blood samples and bilateral kidney tissues were collected. Serum creatinine(SCr) and blood urea nitrogen(BUN) levels were measured to evaluate renal injury and overall therapeutic efficacy. Serum levels of superoxide dismutase(SOD),malondialdehyde (MDA),catalase(CAT),glutathione peroxidase(GSH-Px),and total antioxidant capacity(T-AOC)were assessed to determine the degree of oxidative stress. Renal structural alterations were examined by hematoxylin- eosin(HE)staining,and renal apoptosis was evaluated via immunohistochemical staining for Caspase-3 protein expression. [Results] 1)Compared to the Sham group,the CIAKI group showed significantly elevated SCr and BUN levels(P<0.001),while the EGB+CIAKI group exhibited significantly reduced SCr and BUN levels compared to the CIAKI group(P<0.05). 2)Relative to Sham goup,the CIAKI group demonstrated significantly lower activities of T-AOC,SOD,GSH-Px,and CAT(P<0.01)and significantly higher MDA content(P<0.001). The EGB+CIAKI group had significantly higher SOD and GSH-Px activities(P<0.05)and significantly lower MDA content(P<0.01)compared to the CIAKI group. 3)Renal injury scores were significantly increased in the CIAKI group versus Sham group(P<0.001),whereas the EGB+CIAKI group showed significantly lower scores than the CIAKI group(P<0.001). No significant renal pathological changes were observed in the EGB group. 4)The area of Caspase-3-positive staining cells was significantly larger in the CIAKI group compared to Sham group(P<0.001), and significantly reduced in the EGB+CIAKI group relative to the CIAKI group(P<0.001). [Conclusion] EGB confers renoprotective effects in a rat model of CI-AKI,potentially through modulating oxidative stress balance,enhancing antioxidant enzyme activity,and mitigating secondary oxidative stress damage.
Key words:  contrast-induced acute kidney injury  Ginkgo biloba extract  oxidative stress
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