摘要
目的探讨香叶木素对大鼠肝纤维化的影响及其机制。方法将60只SPF级SD雄性大鼠随机分为A~F组,每组各10只。除A组外均建立四氯化碳(CCl 4)诱导的肝纤维化模型共10周。从第11周开始,D、E、F组分别灌胃50.0、25.0、12.5 mg/kg香叶木素,C组灌胃25.0 mg/kg水飞蓟宾,A组和B组均灌胃等体积生理盐水,每日1次,共6周。通过苏木精-伊红(HE)染色观察各组大鼠肝组织形态学,通过Masson染色观察各组大鼠肝组织纤维化程度,通过荧光探针法检测各组大鼠肝组织中活性氧(ROS)水平,通过RT-qPCR检测各组大鼠肝组织中还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2)、核苷酸结合寡聚化结构域样受体3(NLRP3)、白细胞介素-1β(IL-1β)mRNA相对表达水平,通过蛋白免疫印迹(WB)法检测各组大鼠肝组织中NOX2、NLRP3、IL-1β相对表达水平。结果与A组相比,B组大鼠肝小叶结构破坏、肝细胞变性坏死、假小叶形成,且伴随炎性浸润和大量纤维组织增生,C~F组肝脏组织上述病理变化均较B组明显缓解,其中D组缓解程度最高;C~F组大鼠肝组织中ROS荧光强度及NOX2、NLRP3、IL-1β的mRNA及其蛋白相对表达水平均显著低于B组(F=93.516~142.879,t=5.270~31.333,P<0.05),且D组上述指标均显著低于C组(t=2.572~8.825,P<0.05),F组上述指标均显著高于C组(t=2.774~16.488,P<0.05)。结论香叶木素可缓解CCl 4诱导的大鼠肝脏形态学病理改变和纤维化,其作用机制可能与抑制肝组织中的NOX2信号通路,降低ROS水平,进而下调NLRP3和IL-1β的表达有关。
Objective To investigate the effect of diosmetin on rats with liver fibrosis and its mechanism.Methods A total of 60 specific pathogen-free male Sprague-Dawley rats were randomly divided into groups A,B,C,D,E,and F,with 10 rats in each group.All rats except those in group A were used to establish a model of liver fibrosis induced by carbon tetrachloride(CCl 4)for 10 weeks.Since week 11,the rats in groups D,E,and F were given diosmetin by gavage at a dose of 50.0,25.0,and 12.5 mg/kg,respectively,those in group C were given 25.0 mg/kg silybin by gavage,and those in groups A and B were given an equal volume of normal saline,once a day for 6 weeks.HE staining was used to observe liver histomorphology,and Masson staining was used to observe the degree of liver fibrosis in each group;the fluorescent probe method was used to measure the level of reactive oxygen species(ROS)in rat liver tissue;RT-qPCR was used to measure the relative mRNA expression levels of nicoti-namide adenine dinucleotide phosphate oxidase type 2(NOX2),nucleotide-binding oligomerization domain-like receptor 3(NLRP3),and interleukin-1β(IL-1β)in rat liver tissue,and Western blot(WB)was used to measure the relative protein expression levels of NOX2,NLRP3,and IL-1βin rat liver tissue.Results Compared with group A,group B showed structural da-mage of hepatic lobules,hepatocyte degeneration and necrosis,and pseudolobule formation,with inflammatory infiltration and extensive fibrous tissue proliferation,and compared with group B,groups C,D,E,and F had significant alleviation of the above pathological changes,with the highest degree of alleviation in group D.Compared with group B,groups C,D,E,and F had signi-ficantly lower ROS fluorescence intensity and relative mRNA and protein expression levels NOX2,NLRP3,and IL-1β(F=93.516-142.879,t=5.270-31.333,P<0.05),and compared with group C,group D had significantly lower indicators(t=2.572-8.825,P<0.05)and group F had significantly higher indicators(t=2.774-16.488,P<0.05).Conclusion Diosmetin can alleviate liver pathological changes and fibrosis in rats induced by CCl 4,possibly by inhibiting the NOX2 signaling pathway,reducing the level of ROS,and downregulating the expression of NLRP3 and IL-1βin liver tissue.
作者
谭莉霞
华静
闫春晓
王航宇
董勇
魏书堂
TAN Lixia;HUA Jing;YAN Chunxiao;WANG Hangyu;DONG Yong;WEI Shutang(Department of Gastroenterology,The First Affiliated Hospital of Henan University,Kaifeng 475001,China)
出处
《精准医学杂志》
2025年第6期511-515,521,共6页
Journal of Precision Medicine
基金
开封市科技攻关计划(农业社发领域)项目(190-3099)。
