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邵琰,牟微娜,俞莹莹.山茱萸提取物经COX-2/Nrf2信号通路对脓毒症大鼠肝损伤的改善作用[J].浙江中西医结合杂志,2021,31(4):
山茱萸提取物经COX-2/Nrf2信号通路对脓毒症大鼠肝损伤的改善作用
Effect of cornus officinalis extract on liver injury in sepsis rats via COX-2/Nrf2 signal pathway
投稿时间:2020-09-11  修订日期:2021-03-17
DOI:
中文关键词:  山茱萸提取物  COX-2/Nrf2信号通路  脓毒症  肝损伤
英文关键词:Cornus officinalis extract  COX-2/Nrf2 signaling pathway  Sepsis  Liver injury
基金项目:
作者单位E-mail
邵琰 台州市中心医院急诊医学科 shaoyanyan8893@163.com 
牟微娜 台州市立医院中西医结合科 浙江 台州  
俞莹莹 台州市中心医院急诊医学科 浙江 台州  
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中文摘要:
      目的:探讨山茱萸提取物经环氧化酶-2(COX-2)/NF-E2相关因子2(Nrf2)信号通路对脓毒症大鼠肝损伤的改善作用。方法:将60只SPF级成年雄性SD大鼠,随机分为假手术组、模型组、山茱萸低、中、高剂量组和乌司他丁组,每组10只,除假手术组外,其他各组采用盲肠结扎穿孔术建立脓毒症大鼠模型。造模1h后,山茱萸低、中、高剂量组分别灌胃4g/kg、8g/kg、12g/kg的山茱萸提取物,灌胃体积10mL/kg,同时尾静脉注射2mL的生理盐水;乌司他丁组尾静脉注射10万U/kg的乌司他丁,注射体积2mL,同时灌胃10mL/kg的生理盐水;假手术组和模型组分别灌胃(10mL/kg)和尾静脉注射(2mL)生理盐水,24 h后对大鼠肝组织进行病理学观察,检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和胆红素(BIL)水平,检测肝组织中谷胱甘肽(GSH)、髓过氧化物酶(MPO)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、COX-2、Nrf2和血红素氧化酶-1(HO-1)蛋白水平。结果:假手术组未见病理损害;模型组见大量炎性细胞浸润,肝细胞水肿和坏死,肝索及肝窦消失;各山茱萸剂量组和乌司他丁组可见不同程度淤血、肝窦轻度扩张和炎性细胞浸润,但其损伤程度明显轻于模型组,且山茱萸高剂量组和乌司他丁组无明显差异。与假手术组比较,其余各组大鼠血清中ALT、AST、BIL、肝组织中MPO、IL-6、TNF-α和COX-2蛋白水平增加,GSH、Nrf2和HO-1蛋白水平降低(P<0.05);与模型组比较,各山茱萸剂量组大鼠血清中ALT、AST、BIL、肝组织中MPO、IL-6、TNF-α和COX-2蛋白水平降低,GSH、Nrf2和HO-1蛋白水平增加,呈剂量依赖性(P<0.05);乌司他丁组和山茱萸高剂量组各指标无明显差异(P>0.05)。结论:山茱萸提取物在脓毒症大鼠肝损伤中起保护作用,其机制可能与COX-2/Nrf2信号通路有关。
英文摘要:
      Objective: To investigate the effect of cornus officinalis extract on liver injury in sepsis rats via cyclooxygenase-2(COX-2)/NF-E2-related factor 2(Nrf2) signal pathway. Methods: Sixty adult male SD rats of SPF grade were randomly divided into sham operation group, model group, low, medium and high dose cornus officinalis extract groups and ulinastatin group, with 10 rats in each group. Except for the sham operation group, the sepsis rat models were established by cecal ligation and perforation in other groups. One hour after the model was established, the low, medium and high dose cornus officinalis extract groups were intragastrically administered with 4 g/kg, 8 g/kg and 12 g/kg of cornus officinalis extract, with the volume of 10 ml/kg, and the tail vein was injected with 2 mL normal saline; in the ulinastatin group, 100 000 U/kg ulinastatin was injected into the tail vein with a volume of 2 mL, and 10 ml/kg normal saline was intragastrically administered at the same time; the sham operation group and model group were intragastric (10 ml/kg) and tail vein injection (2 mL) of normal saline. After 24 hours, the rat liver tissue pathology, the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST) and bilirubin(BIL) in serum, glutathione(GSH), myeloperoxidase(MPO), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), COX-2, Nrf2 and heme oxygenase-1(HO-1) protein in liver tissue were measured. Results: There was no pathological damage in the sham operation group. A large number of inflammatory cell infiltration, hepatocyte edema and necrosis, hepatic cord and hepatic sinus disappeared in the model group. The different degrees of congestion, slight expansion of the sinusoids and inflammatory cell infiltrationwere observed in the all cornus officinalis extract dose groups and the ulinastatin group, but the degree of damage was significantly lighter than the model group, there was no significant difference between high dose cornus officinalis extract group and ulinastatin group. Compared with sham operation, the levels of serum ALT, AST, BIL, liver tissue MPO, IL-6, TNF-α and COX-2 protein were significantly increased, and GSH, Nrf2 and HO-1 protein decreased(P<0.05). Compared with the model group, the levels of serum ALT, AST, BIL, liver tissue MPO, IL-6, TNF-α and COX-2 protein in each dose group of cornus officinalis extract were significantly decreased, and the levels of GSH, Nrf2 and HO-1 protein increased, it was dose-dependent(P<0.05). There was no significant difference in all indexes between the high dose cornus officinalis extract groups and the ulinastatin group(P>0.05). Conclusion: The extract of cornus officinalis plays a protective role in the liver injury of sepsis rats, and its mechanism may be related to COX-2 / Nrf2 signal pathway.
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