摘要
目的研究裂果薯总皂苷(SFSP)对四氯化碳(CCl_4)诱导的肝纤维化大鼠的作用及其机制。方法将♂SD大鼠随机分为5组:正常对照组、模型组、秋水仙碱组(Col)、SFSP低剂量组(SFSP-L)、SFSP高剂量组(SFSP-H)。连续给药4周后,检测各组大鼠ALT、AST和羟脯氨酸的含量;ELISA法检测肝纤维化标志物;HE染色观察肝组织病理学改变;Masson染色观察肝纤维化程度;透射电镜观察肝超微结构变化;qPCR法检测α-SMA、TGF-β1、Smad4、Smad7 mRNA的表达情况。结果肝纤维化模型组AST、ALT及CⅣ、PCⅢ、LN、HA、Hyp反映肝损伤和纤维化进程的指标,均明显升高(P<0.05),而SFSP-H组和Col组明显降低上述指标含量,HE、Masson染色结果与之一致;SFSP明显抑制TGF-β1、Smad4、α-SMA mRNA的表达(P<0.01),升高Smad7的表达(P<0.01)。结论 SFSP通过抑制TGF-β1/Smad信号通路,明显抑制大鼠肝纤维化程度。
Aim To study the effect of total saponins of Schizocapsa plantaginea Hance (SFSP) on hepatic fibrosis in rats induced by CCl 4 and to investigate the molecular mechanisms of these effects. Methods ♂SD rats were randomly divided into five groups: normal control group,model group,colchicine (Col) as positive control group,low-dose SFSP group (SFSP-L),and high-dose SFSP group (SFSP-H).After four weeks of continuous administration,serum AST,ALT and hydroxyproline (Hyp) were measured by biochemical detection method.The four indicators of liver fibrosis (CIV,PCⅢ,LN,HA) in serum were measured by enzyme linked immunosorbent assay.The location of liver fibrous tissues was observed by Masson staining.Liver sections were stained with HE,and observed for pathologic changes.Liver ultrastructural changes were observed using a transmission electron microscope.The expressions of mRNA of α-smooth muscle actin(α-SMA),transforming growth factor β1 (TGF-β1),Smad4 and Smad7 in liver were detected by qPCR. Results In the liver fibrosis model group,the contents of AST,ALT and CIV,PCⅢ,LN,HA,Hyp reflecting liver injury and fibrosis significantly increased ( P <0.05),while in SFSP-H group and Col group the contents of the above indicators were significantly reduced,and the pathological results of liver tissues were consistent with it.SFSP significantly inhibited the expression of TGF-β1,Smad4 and α-SMA mRNA ( P <0.01),and increased the expression of Smad7 as well( P <0.01). Conclusion SFSP has an antifibrogenic effect through down-regulating the TGF-β1/Smad signaling pathway in rats.
作者
廖智红
陈燕燕
黄修影
甘日植
罗舜仁
吕美娴
刘布鸣
梁钢
LIAO Zhi-hong;CHEN Yan-yan;HUANG Xiu-ying;GAN Ri-zhi;LUO Shun-ren;LYU Mei-xian;LIU Bu-ming;LIANG Gang(Pharmaceutical College,Guangxi Medical University,Nanning530021,China;Dept of Pharmacy,the Second People's Hospital of Qinzhou,Qinzhou Guangxi535000,China;Dept of Pharmacy,the Affiliated Ruikang Hospital of Guangxi Traditional Chinese Medical College,Nanning530011,China;Guangxi Key Lab of Traditional Chinese Medicine Quality Standards,Nanning530022,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第5期624-629,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81460620)
广西省自然科学基金重点项目(No 2014GXNSFDA118025)
关键词
裂果薯
裂果薯总皂苷
肝纤维化
胶原合成
转化生长因子β1
TGF-Β1/SMAD信号通路
Schizocapsa plantaginea Hance
total saponins of Schizocapsa plantaginea Hance
hepatic fibrosis
collagen synthesis
TGF-β1
TGF-β1/Smad signaling pathway
