摘要
目的探究虎杖苷对大鼠肝脏缺血再灌注损伤(HIR)的保护作用及其与核因子E2相关因子2(Nrf2)/血红素氧合酶1(HO⁃1)信号通路的作用关系。方法采用随机数字法将40只SD大鼠分为5组(每组8只),即假手术组、模型组、低剂量虎杖苷组、高剂量虎杖苷组、高剂量虎杖苷联合Nrf2抑制剂组。建立大鼠肝脏缺血再灌注损伤模型,并于造模前连续3 d给予不同剂量虎杖苷或联合Nrf2抑制剂ML385预处理。再灌注6 h后,检测各组大鼠血清谷丙转氨酶(ALT)和天门冬氨酸氨基转移酶(AST)活性、白细胞介素1β(IL⁃1β)、白细胞介素6(IL⁃6)和肿瘤坏死因子α(TNF⁃α)表达水平以及肝组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平;HE染色观察大鼠肝组织病理特征并进行病理评分;TUNEL法检测大鼠肝组织细胞凋亡情况;Western blot检测肝组织核蛋白Nrf2、全蛋白HO⁃1、Bax、Bcl⁃2及cleaved caspase⁃3等表达水平。结果与假手术组比较,模型组大鼠肝组织病理评分、血清ALT与AST活性及IL⁃1β、IL⁃6和TNF⁃α水平升高,肝组织细胞凋亡率、MDA水平以及Nrf2、HO⁃1、Bax、cleaved caspase⁃3蛋白表达增加,而SOD活性和Bcl⁃2表达水平降低,组间差异显著。高剂量虎杖苷能显著缓解模型大鼠肝组织损伤,降低炎症水平、氧化应激以及细胞凋亡,并且促进Nrf2及HO⁃1的蛋白表达,组间差异显著。ML385处理可抑制高剂量虎杖苷的干预效果。结论虎杖苷可能通过激活Nrf2/HO⁃1信号通路,抑制HIR诱导的炎症、氧化应激以及肝细胞凋亡,改善大鼠肝脏缺血再灌注损伤。
AIM To investigate the protective effect of polydatin on hepatic ischemia⁃reperfusion(HIR)injury and its relationship with the signaling pathway of nuclear factor E2⁃related factor 2(Nrf2)/heme oxygenase⁃1(HO⁃1)in rats.METHODS Forty male SD rats(8 in each group)were randomly divided into sham surgery group,model group,groups for interventions of low dose or high dose polydatin,and high dose of polydatin+Nrf2 inhibitor ML385 group.Three days prior to the establishment of HIR rat models,the previously designed plan was implemented in the rats.Six hours after reperfusion,the rats were subjected to the following determinations:alanine aminotransferase(ALT)and aspartate aminotransferase(AST),the expression level of inflammatory factors tumor necrosis factorα(TNF⁃α),Interleukin 1β(IL⁃1β)and Interleukin 6(IL⁃6),and levels of oxidative stress superoxide dismutase(SOD),malondialdehyde(MDA)in liver;the hepatic pathological characteristics and pathological assessment by HE staining;the hepatocytes apoptosis by TUNEL method;and the hepatic expression of nucleoprotein Nrf2,total protein(HO⁃1),Bax,Bcl⁃2 and cleaved caspase⁃3 by Western blot.RESULTS Compared with the sham surgery group,the model group was observed with obvious hepatic damage,and significantly increased pathological score,activity of ALT and AST,content of TNF⁃α,IL⁃1βand IL⁃6(P<0.05),significantly increased apoptosis rate,MDA content,expression of Nrf2,HO⁃1,Bax and cleaved caspase⁃3 proteins(P<0.05),and markedly decreased activity of SOD and expression of Bcl⁃2(P<0.05).In contrast with the model group,the group intervened with high dose polydatin showed significantly relieved liver tissue damage,lower pathological score,significantly decreased activity of ALT and AST,content of TNF⁃α,IL⁃1βand IL⁃6(P<0.05),significantly decreased apoptosis rate,MDA content,expression of Bax and cleaved caspase⁃3 proteins(P<0.05),and markedly increased activity of SOD and expression of Nrf2,HO⁃1 and Bcl⁃2 proteins(P<0.05).However
作者
徐志广
张朴花
XU Zhi-guang;ZHANG Pu-hua(Nanhua Hospital Affliated to University of South China,Hengyang 421002,China)
出处
《中成药》
CAS
CSCD
北大核心
2021年第2期362-368,共7页
Chinese Traditional Patent Medicine
