摘要
目的研究薯蓣皂苷对小鼠肝纤维化模型肝组织损伤和PI3K/Akt信号通路的影响。方法用四氯化碳构建肝纤维化小鼠模型。按照体重将小鼠随机分为5组:正常组、模型组、水飞蓟素组和低、高剂量实验组,每组9只。正常组、模型组给予生理盐水灌胃,水飞蓟素组给予100 mg·kg^(-1)水飞蓟素灌胃,低、高剂量实验组分别用50 mg·kg^(-1)薯蓣皂苷、100 mg·kg^(-1)薯蓣皂苷灌胃,每天1次,连续3周。计算小鼠肝指数,用ELISA法检测肝组织中肿瘤坏死因子-α(TNF-α)含量和血清中谷丙转氨酶(GPT)含量,用碱水解法测定肝组织中羟脯氨酸(Hyp)含量,用Western blot法检测肝组织中转化生长因子β1(TGF-β1)、p-Akt、蛋白激酶B(Akt)蛋白表达。结果正常组、模型组、水飞蓟素组和低、高剂量实验组小鼠血清中GPT含量分别为(30.26±2.58),(86.63±7.33),(56.94±6.79),(68.12±4.77)和(52.61±5.81)U·L^(-1);这5组肝组织中Hyp含量分别为(151.01±15.36),(294.15±23.66),(180.49±17.25),(230.41±17.48)和(172.30±16.65)μg·g-1;这5组肝指数分别为(4.82±0.41)%,(8.26±0.84)%,(5.79±0.61)%,(6.83±0.63)%和(5.63±0.51)%;这5组肝组织中TNF-α含量分别为(2.26±0.21),(5.95±0.84),(3.21±0.30),(4.18±0.62)和(3.06±0.55)pg·mg-1;这5组TGF-β1蛋白表达量分别为0.20±0.03,0.48±0.09,0.31±0.05,0.36±0.05和0.29±0.04;这5组p-Akt/Akt表达量分别为0.23±0.03,0.45±0.06,0.26±0.04,0.35±0.04和0.29±0.05。上述指标,模型组与正常组比较,差异均有统计学意义(均P<0.05);低、高剂量实验组、水飞蓟素组与模型组比较,差异均有统计学意义(均P<0.05);高剂量实验组与低剂量实验比较,差异均有统计学意义(均P<0.05)。结论薯蓣皂苷改善小鼠肝纤维化模型肝组织炎症和肝组织纤维化,机制可能与阻断PI3K/Akt信号有关。
Objective To study the effects of dioscin on liver tissue damage and PI3K/Akt signaling pathway in a mouse liver fibrosis model.Methods Liver fibrosis mouse model was induced by carbon tetrachloride.The mice were randomly divided into 5 groups:normal group,mode group,silymarin group,experimental-L group and experimental-H group.Mice in normal group and the model group were orally administered with physiological saline,mice in silymarin group were orally treated with silymarin (100 mg·kg;),while rats in experimenta-L group and experimental-H group were orally administered with dioscin at the dose of 50 and 100 mg·kg;,respectively.All the drugs were administered for consecutive 3 weeks,1times a day.The liver index of mice was calculated.The content of tumor necrosis factor-α(TNF-α) in liver tissue and the content of alanine aminotransferase (GPT) in serum were detected by ELISA method,the content of hydroxyproline (Hyp) in liver tissue was determined by alkaline hydrolysis method,the expression of transforming growth factorβ1 (TGF-β1),p-Akt,and protein kinase B (Akt) in liver tissue were detected by Western blot.Results The serum GPT levels of mice in normal group,model group,silymarin group,experimental-L group and experimental-H group were (30.26±2.58),(86.63±7.33),(56.94±6.79),(68.12±4.77) and(52.61±5.81) U·L;,respectively;the Hyp content of liver tissues in the 5 groups were (151.01±15.36),(294.15±23.66),(180.49±17.25),(230.41±17.48) and (172.30±16.65)μg·g;,respectively;the liver indexes of the 5 groups were (4.82±0.41)%,(8.26±0.84)%,(5.79±0.61)%,(6.83±0.63)%and(5.63±0.51)%,respectively;the TNF-αcontent of liver tissues in the 5 groups were (2.26±0.21),(5.95±0.84),(3.21±0.30),(4.18±0.62) and (3.06±0.55) pg·mg;,respectively;the TGF-β1 protein expression of liver tissues in the 5 groups were 0.20±0.03,0.48±0.09,0.31±0.05,0.36±0.05 and0.29±0.04,respectively;the p-Akt/Akt expression of liver tissues in the 5 groups were 0.23±0.03,0.45±0.06,0.26±0.04,0.35±0.04 and 0.29±0.05,
作者
卢世云
林云
林志辉
王泓力
甘雨桐
LU Shi-yun;LIN Yun;LIN Zhi-hui;WANG Hong-li;GAN Yu-tong(Department of Gastroenterology,Provincial clinical college of Fujian Medical University,Fuzhou 350000,Fujian Province,China;Department of Internal Medicine,South Hospital,Fujian Provincial Hospital,Fuzhou 350000,Fujian Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第20期2834-2837,共4页
The Chinese Journal of Clinical Pharmacology
基金
福建省自然科学基金资助项目(2018Y0013)。
