白藜芦醇改善野百合碱所致大鼠肝损伤机制的初步研究  

A preliminary study on the mechanism of resveratrol in improving rat liver injury induced by monocrotaline

作　　者：卫霞 宋育林[1,2] 涂倩倩 徐魁 Wei Xia;Song Yulin;Tu Qianqian;Xu Kui(Dept of Gastroenterology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;The Key laboratory of digestive disease of Anhui Province,Hefei 230022;Dept of Gastroenterology,Lu’an Hospital of Anhui Medical University,Lu’an 237016)

机构地区：[1]安徽医科大学第一附属医院消化内科,合肥230022 [2]安徽省消化系统疾病重点实验室,合肥230022 [3]安徽医科大学附属六安医院消化内科,六安237016

出　　处：《安徽医科大学学报》2022年第7期1111-1115,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽高校自然科学研究项目(编号:KJ2016A337);2016-2018年安徽高校科研平台创新团队建设项目(编号:皖教秘科[2015]49号)。

摘　　要：目的探讨沉默信息调节因子1(SIRT1)激动剂白藜芦醇对野百合碱所致肝窦阻塞综合征的保护作用及其可能机制。方法32只雄性SD大鼠随机分为对照组(8只)、野百合碱组(12只)和白藜芦醇组(12只)。野百合碱组和白藜芦醇组给予野百合碱(160 mg/kg)单次灌胃;白藜芦醇组于野百合碱灌胃前1 d开始每天给予白藜芦醇溶液(30 mg/kg)腹腔注射。在给予野百合碱2 d后结束实验。检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBiL)和肝组织内谷胱甘肽(GSH)和丙二醛(MDA)水平,观察肝脏病理变化,应用Western blot检测肝脏SIRT1、HIF-1α和VEGF蛋白的表达水平。结果与对照组相比,野百合碱组大鼠单次灌胃后血清ALT、AST及TBiL有所升高(均P<0.01),肝脏GSH水平降低(P<0.01)、MDA升高(P<0.01);肝脏组织病理学可见肝细胞排列紊乱,并出现变性、坏死,肝窦淤血扩张,中央静脉内皮损伤,SIRT1蛋白的表达水平降低(P<0.01),HIF-1α和VEGF蛋白的表达水平有所增加(P<0.01)。使用白藜芦醇干预后,血清ALT、AST、TBiL指标下降(P<0.05或P<0.01),肝脏GSH水平升高(P<0.01)、MDA降低(P<0.01),并可以抑制野百合碱引起的肝脏病理损伤,SIRT1蛋白的表达水平升高(P<0.01),HIF-1α和VEGF蛋白表达下调(P<0.01)。结论白藜芦醇可以改善野百合碱引起的大鼠肝窦阻塞综合征,其机制与激活SIRT1、抑制HIF-1α/VEGF信号通路及抗氧化应激相关。Objective To investigate the protective effect and mechanisms of silent information regulator 1(SIRT1) agonist resveratrol on monocrotaline-induced Hepatic sinusoidal obstruction syndrome(HSOS) in rats. Methods Thirty-two male Sprauge-Dawley(SD) rats were randomly divided into three group, with 8 rats in the control group and 12 rats in each of the monocrotaline group and resveratrol group. The monocrotaline group and resveratrol group were given monocrotaline(160 mg/kg) by single gavage. The resveratrol group was intraperitoneally injected with resveratrol solution [30 mg/(kg·d)] one day before intragastric administration. The experiment was terminated 2 days after the monocrotaline administration. Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBiL), glutathione(GSH) and malondialdehyde(MDA) in liver homogenate were detected. The pathological change of liver tissue was observed. The protein expression levels of SIRT1, hypoxia-inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF) in liver were detected by Westernblot. Results Compared with the control group, the serum ALT, AST and TBiL in monocrotaline group increased(all P<0.01), GSH in liver homogenate decreased(P<0.01), MDA increased(P<0.01). Disordered arrangement, degeneration and necrosis of liver cells, congestion and dilation of hepatic sinuses and damage of central vein endothelium were observed. SIRT1 decreased(P<0.01), HIF-1α and VEGF protein expression increased(all P<0.01). After resveratrol treatment, serum ALT, AST and TBiL obviously decreased( P<0.05;P<0.05;P<0.01). GSH in liver homogenate increased(P<0.01), MDA decreased(P<0.01). And resveratrol also could inhibit the liver pathological damage caused by monocrotaline. SIRT1 protein expression increased(P<0.01), HIF-1α and VEGF protein expression also decreased(all P<0.01). Conclusion Resveratrol can improve Hepatic sinusoidal obstruction syndrome caused by monocrotaline in rats, and the mechanism is related to its activation of SIRT

关 键 词：野百合碱 肝损伤 白藜芦醇 SIRT1 HIF-1Α 氧化应激 大鼠 

分 类 号：R575[医药卫生—消化系统] R99[医药卫生—内科学]