摘要
目的探究金钗石斛生物碱(DNLA)对对乙酰氨基酚(APAP)所致小鼠急性肝损伤的保护作用及机制。方法30只C57BL/6J雄性小鼠随机分为空白组,DNLA组(DNLA,20 mg/kg),APAP模型组(APAP,300 mg/kg),APAP+DNLA低、高剂量(10、20 mg/kg)组,每组6只。灌胃给药7 d后,腹腔注射APAP溶液建立急性肝损伤模型,检测血清ALT、AST及肝组织GSH、SOD活性和MDA水平,HE染色观察肝组织病理变化,Western blot检测肝组织CYP2E1、Nrf2、GCLC、HO-1、NQO1、GPX1的蛋白表达水平;免疫荧光检测AML-12细胞中Nrf2蛋白的表达。结果与空白组比较,APAP模型组小鼠血清ALT、AST活性显著升高,肝组织MDA含量显著增加(P<0.01),SOD和GSH活性明显降低(P<0.05),CYP2E1蛋白表达增加(P<0.01),核蛋白Nrf2和GCLC、HO-1、NQO1蛋白表达明显降低(P<0.05),肝组织出现大片坏死及炎症细胞浸润。与APAP模型组比较,DNLA可显著降低小鼠血清中ALT、AST活性(P<0.01),升高肝组织SOD、GSH活性(P<0.05)、降低MDA水平(P<0.01),亦可降低CYP2E1蛋白表达(P<0.05),增加GCLC、NQO1、HO-1、GPX1及核内Nrf2的蛋白表达(P<0.01),改善肝脏组织病理损伤。结论DNLA能够改善APAP引起的小鼠急性肝损伤,其作用机制可能与激活Nrf2信号通路,增强小鼠肝脏抗氧化能力有关。
Objective To investigate the protective effect and mechanism of dendrobium nobile lindl.alkaloids against acetaminophen-induced acute liver injury in mice.Methods Thirty male C57BL/6J mice were randomly divided into five groups:control group,DNLA group(20 mg/kg),APAP group(300 mg/kg),APAP+DNLA low-dose group(10 mg/kg),APAP+DNLA high-dose group(20 mg/kg),with 6 mice in each group.Acute liver injury was induced by intraperitoneal injection of APAP solution after administration by gavage.The levels of ALT,AST in serum,MDA,SOD and GSH in liver tissue were determined by kits.The pathological morphological changes were determined by HE staining.The expression of CYP2E1,Nrf2,GCLC,HO-1,NQO1,and GPX1 proteins were determined by Western blot.Nrf2 protein expression in AML-12 was detected by immunofluorescence.Results Compared with the control group,the ALT,AST and MDA levels in APAP group were significantly increased(P<0.01),the activities of SOD and GSH was significantly decreased(P<0.05).The necrosis and inflammatory infiltration were increased in liver.The CYP2E1 expression was significantly increased(P<0.01),while the nuclear Nrf2,GCLC,HO-1,NQO1 expression was significantly reduced(P<0.05).Compared with the APAP group,DNLA reduced the levels of ALT and AST in serum(P<0.01).The activities of SOD and GSH were elevated(P<0.05),and the levels of MDA were reduced in liver(P<0.01).The expression level of CYP2E1 was significantly reduced(P<0.05),and the nuclear Nrf2,GCLC,NQO1,HO-1,GPX1 levels in liver were significantly increased(P<0.01).The pathological injury of the liver was significantly alleviated.Conclusion DNLA ameliorate APAP-induced acute liver injury in mice,which may be related to the activation of Nrf2 signaling pathway and enhanced the antioxidant capacity of liver.
作者
蒋勇炫
毛黔华
林夏萍
徐云燕
李映莹
黄波
杨媛
吴芹
Jiang Yongxuan;Mao Qianhua;Lin Xiaping;Xu Yunyan;Li Yingying;Huang Bo;Yang Yuan;Wu Qin(Key Laboratory of Basic Pharmacology of Ministry of Education,Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563006,China;Department of Gastroenterology,Digestive Disease Hospital,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563000,China;Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology,Zunyi Guizhou 563006,China)
出处
《遵义医科大学学报》
2024年第11期1047-1053,1060,共8页
Journal of Zunyi Medical University
基金
国家自然科学基金资助项目(NO:82060750,NO:81560682)
贵州省厅科技厅自然科学基金资助项目[NO:黔科合基础(2023)一般558]。
关键词
金钗石斛生物碱
急性肝损伤
对乙酰氨基酚
保护作用
氧化应激
dendrobium nobile lindl.alkaloids
acute liver injury
acetaminophen
protective effect
oxidative stress
