Objective：To study the effect of total flavonoids of Astmgali Radix（TFA）on liver cirrhosis induced with dimethylnitrosamine（DMN）in rats,and the effect on peroxisome proliferator-activated receptorγ（PPARγ）,unc...Objective：To study the effect of total flavonoids of Astmgali Radix（TFA）on liver cirrhosis induced with dimethylnitrosamine（DMN）in rats,and the effect on peroxisome proliferator-activated receptorγ（PPARγ）,uncoupling protein 2（UCP2）and farnesoid X receptor（FXR）.Methods：Fifty-three Sprague-Dawley rats were randomly divided into a control group（10 rats）and a DMN group（43 rats）.Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group（14 rats）,a low-dosage TFA group（14 rats）and a high-dosage TFA group（15 rats）in the 3rd week.Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low-and high-TFA groups,respectively.At the end of the experiment blood and liver samples were collected.Serum liver function and liver tissue hydroxyproline content were determined.hematoxylin-eosin（HE）,Sirus red and immunohistochemical stainings of collagenⅠ,smooth muscle actin（α-SMA）was conducted in paraffinembedded liver tissue slices.Real time polymerase chain reaction（PCR）was adopted to determine PPARγ,UCP2 and FXR m RNA levels.Western blot was adopted to determine protein levels of collagenⅠ,α-SMA,PPARγ,UCP2 and FXR.Results：Compared with the model group,TFA increased the ratio of liver/body weight（low-TFA group P〈0.05,high-TFA group P〈0.01）,improved liver biochemical indices（P〈0.01 for ALT,AST,GGT in both groups,P〈0.05 for albumin and TBil in the high-TFA group）and reduced liver tissue hydroxproline content（P〈0.01 in both groups）in treatment groups significantly.HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition,alleviated formation and extent of liver pseudolobule.CollagenⅠandα-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group.TFA could increase PPARγ,it regulated target UCP2,and FXR levels significantly compared with the model group（in the low-TFA group all P〈0.05,in the high group all P〈0.01）.Conclusions：TFA could improve liver function,alleviate liver pathological changes,and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis.The antifibrotic effect of TFA was through regulating PPARγsignal pathway and the interaction with FXR.展开更多
基金Supported by the Shanghai Natural Science Foundation(N0.10ZR1430700)Three-Year Plan of Action of Traditional Chinese Medicine in Shanghai(No.ZY3-RCPY-1-1011)
文摘Objective：To study the effect of total flavonoids of Astmgali Radix（TFA）on liver cirrhosis induced with dimethylnitrosamine（DMN）in rats,and the effect on peroxisome proliferator-activated receptorγ（PPARγ）,uncoupling protein 2（UCP2）and farnesoid X receptor（FXR）.Methods：Fifty-three Sprague-Dawley rats were randomly divided into a control group（10 rats）and a DMN group（43 rats）.Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group（14 rats）,a low-dosage TFA group（14 rats）and a high-dosage TFA group（15 rats）in the 3rd week.Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low-and high-TFA groups,respectively.At the end of the experiment blood and liver samples were collected.Serum liver function and liver tissue hydroxyproline content were determined.hematoxylin-eosin（HE）,Sirus red and immunohistochemical stainings of collagenⅠ,smooth muscle actin（α-SMA）was conducted in paraffinembedded liver tissue slices.Real time polymerase chain reaction（PCR）was adopted to determine PPARγ,UCP2 and FXR m RNA levels.Western blot was adopted to determine protein levels of collagenⅠ,α-SMA,PPARγ,UCP2 and FXR.Results：Compared with the model group,TFA increased the ratio of liver/body weight（low-TFA group P〈0.05,high-TFA group P〈0.01）,improved liver biochemical indices（P〈0.01 for ALT,AST,GGT in both groups,P〈0.05 for albumin and TBil in the high-TFA group）and reduced liver tissue hydroxproline content（P〈0.01 in both groups）in treatment groups significantly.HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition,alleviated formation and extent of liver pseudolobule.CollagenⅠandα-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group.TFA could increase PPARγ,it regulated target UCP2,and FXR levels significantly compared with the model group（in the low-TFA group all P〈0.05,in the high group all P〈0.01）.Conclusions：TFA could improve liver function,alleviate liver pathological changes,and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis.The antifibrotic effect of TFA was through regulating PPARγsignal pathway and the interaction with FXR.
