摘要
探究补骨脂水提物对大鼠肝脏的损伤作用及其潜在机制。选取48只大鼠,随机分为4组:空白组、补骨脂低剂量组(BGZL,6.25 g·kg-1)、补骨脂中剂量组(BGZM,12.5 g·kg-1)和补骨脂高剂量组(BGZH,25 g·kg-1)。给药周期为28 d,每天观察大鼠有无毒性反应和死亡情况。28 d后进行取材,计算大鼠体质量、肝脏器官系数和肝脑比,同时观察肝脏组织形态学变化并检测相关血清学生化指标。结果显示,与空白组相比,各补骨脂给药组大鼠体质量下降,肝脏器官系数和肝脑比升高,肝脏出现肝肿大病变;病理学检查发现,大鼠肝脏出现肝内胆管增生、炎症细胞浸润和肝细胞纤维化。肝功能生化指标结果显示,与空白组相比,BGZL组大鼠谷丙转氨酶(alanine transaminase,ALT)、α-谷胱甘肽S转移酶(α-glutathione S-transferase,α-GST)、总胆汁酸(total bile acid,TBA)等指标显著升高(P<0.05);BGZM组、BGZH组大鼠ALT、TBA、α-GST、谷氨酰转移酶(γ-glutamyl transferase,γ-GT)、嘌呤核苷酸磷酸化酶(purine nucleoside phosphorylase,PNP)、鸟氨酸甲酰基转移酶(ornithine carbamoyltransferase,OCT)、精氨酸酶(arginase,ArgI)等指标显著升高(P<0.05)。与空白组相比,各补骨脂给药组大鼠的胆酸盐外排泵(bile salt export pump,BSEP)、类法尼醇X受体(farnesoid X receptor,FXR)基因以及蛋白表达显著下降(P<0.05),肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、核因子κB(nuclear factor kappaB,NF-κB)、胆固醇7α-羟化酶(cholesterol 7 alpha-hydroxylase,CYP7A1)基因以及蛋白表达显著升高(P<0.05)。研究表明,补骨脂水提物对大鼠产生明显的中毒反应,呈现一定的量-毒关系,表明补骨脂水提物存在一定程度的肝损伤作用,可能是由于补骨脂影响肝脏胆汁酸分泌排泄与诱发炎症。
This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats.Forty-eight rats were randomly assigned into four groups:a blank group and low-(BZGL,6.25 g·kg-1),medium-(BGZM,12.5 g·kg-1),and high-dose(BGZH,25 g·kg-1)Psoraleae Fructus water extract groups.The rats were treated for 28 days,and toxicity and mortality were observed daily.After 28 days,the rats were sacrificed,and the body weight,liver index,and liver-to-brain ratio were calculated.The morphological changes in the liver tissue were observed,and the serum levels of related biochemical indicators were measured.The results showed that compared with the blank group,Psoraleae Fructus water extracts of different doses decreased the body weight,increased the liver index and liver-to-brain ratio,and caused liver hypertrophy and pathological changes.Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia,inflammatory cell infiltration,and liver cell fibrosis.Compared with the blank group,BGZL elevated the levels of alanine transaminase(ALT),α-glutathione S-transferase(α-GST),and total bile acid(TBA)(P<0.05),and BGZM and BGZH elevated the levels of ALT,TBA,α-GST,γ-glutamyl transferase(γ-GT),purine nucleoside phosphorylase(PNP),ornithine carbamoyltransferase(OCT),and arginase(ArgI)(P<0.05).Compared with the blank group,Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP)and farnesoid X receptor(FXR)and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α),nuclear factor kappaB(NF-κB),and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05).The results suggested that Psoraleae Fructus water extract caused toxicity in rats,showing a dose-toxicity relationship.Psoraleae Fructus water extract may cause liver damage,which may be due to its effect on liver bile acid secretion and induction of inflammation.
作者
徐博
姚广涛
解骏
冉磊
阿欣雨
肖涟波
XU Bo;YAO Guang-tao;XIE Jun;RAN Lei;A Xin-yu;XIAO Lian-bo(Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Institute of Arthritis Research in Integrative Medicine,Shanghai Academy of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2023年第16期4459-4466,共8页
China Journal of Chinese Materia Medica
基金
上海市“科技创新行动计划”自然科学基金项目(22ZR1453100)
上海中医药大学医养结合高水平科创项目(YYKC-2021-01-001)。
关键词
补骨脂水提物
肝损伤
胆汁淤积
炎症反应
Psoraleae Fructus water extract
liver injury
cholestasis
inflammation
