An Experimental Study On The Intervention Of Kangxian Yicai Recipe On Precancerous Lesions Of Liver Cancer Based On HGF/c-Met Signaling Pathway

ObjectivePrimary liver cancer(PLC)is a malignant disease with high incidence and mortality,which often exPeriences the Process of chronic hePatitis→liver cirrhosis→hePatic Precancerous lesion→liver cancer.HePaticPrecancerous lesion refers to the abnormal liver tissue that is Prone to cancer,and there is increasing evidence thathePatic Precancerous lesion is an imPortant stage and favorable time to Prevent the occurrence of liver cancer,therefore,it is widely valued.Based on tutor’s clinical and exPerimental work,wedeveloPKangxian Yi’ai Formula.On the basis of Previous research,we observehePatocyte growth factor(HGF)/c-Met signaling Pathway exPression inhePatic in Precancerous lesions and the effect ofKangxian Yi’ai formula so as to clarify the mechanism of Kangxian Yi’ai formula in the treatment of hePatic Precancerous lesion.MethodTo establish the rats mode of hePatic Precancerous lesion based on liver cirrhosis and to intervene by different doses of Kangxian Yi’ai formula.ComPared the difference of rats in each grouP on the general situation and the liverPathological change,and determined the exPression levels ofglutathione-S-transferases-π(GST-Pi),Proliferating cell nuclear antigen(PCNA),HGF and c-Metby using immunohistochemistry andwestern blot.Results1.The general conditionmanifestations:normal grouP rats were in good condition during the exPeriment.The rats in the model grouP and Kangxian Yi’ai formula grouPs began to show signs of disease after the 4th week by diethylnitrosamine(DEN)to inducehePatic Precancerous lesion.In the 10 the week,the disease Performance of Kangxian Yi’ai formula grouPswere less than that of the model grouP.ExcePt for lavage error,four rats were died in the model grouP,two rats were died in thelow-doseKangxian Yi’ai formula grouP,one rat was died in the medium-doseKangxian Yi’ai formula grouP,and there was no death in the high-doseKangxian Yi’ai formula grouP.2.The gross morPhology manifestations:the liver was soft,reddish and smoothin the normal grouP.In the model grouP,the liver was hard and dark red,with diffuse nodules on the surface and a large volume of grayish brown nodules.ComPared with model grouP,the Kangxian Yi’ai formulaeach dose grouPs are relatively lighter,esPecially in the high-doseKangxian Yi’ai formula grouP,which rats liverswere tough and reddish,with a relatively smooth surface,granules and rare nodules.3.The hePatic histoPathologicalmanifestations:The liver HE staining showed that the liver lobule structure was intact in the normal grouP,without inflammatory cell infiltration,fibroPlasia,abnormal hyPerPlasia.Normal lobular architecture by fibrous interval segmentation,extensive Pseudolobule formation,a large number of inflammatory cells infiltrate in the catchment area,hyPerPlasia,a large number of hePatocyte atyPical hyPerPlasia and atyPical hyPerPlasia nodules were obsever in the model grouP.The degree of fibrosis was relatively light and liver cell inflammation,necrosis and hePatocyte atyPical hyPerPlasia were also significantly reduced in the Kangxian Yi’ai formula grouPs.Masson staining showed a small amount of fibrous tissue between the normal grouP.The fibrosis of the model grouP was obvious,withextensive Pseudolobule formation,while the Kangxian Yi’ai formula grouPswere only formed in the PeriPheral fibers of the vascular area,the formation of the false lobule was not obvious.4.Immunohistochemistry:there were only a few GST-Pi and PCNA Positive exPression in the normal grouP.In the model grouP,there were many Positive exPression in the PeriPheral or hePatic lobules,and the area of the Positive exPressionwas significantly decreased in the Kangxian Yi’ai formula grouPs,esPecially in the high-dose grouP(P<0.01).ComPared with the normal grouP,the Positive exPression of c-Met increased significantly in the model grouP(P<0.01).ComPared with the model grouP,the c-Met Positive exPression strength of the treatment grouP was significantly reduced,esPecially in the high-dose grouP(P<0.01).5.Western blot:ComPared with the normal grouP,the exPression levels of GRB2,P-Gabl and P-PLC were significantly increased in the model grouP(P<0.01).ComPared with the model grouP,the exPression levels of GRB2,P-Gabl and P-PLCwere significantly decreased in the medium-doseKangxian Yi’ai formula grouP(P<0.05).ConclusionsKangxian Yi’ai formula can reduce the degree of fibrosis of hePatic Precancerous lesion in rats and inhibit the occurrence and develoPment of hePatic Precancerous lesion,and its mechanism may be activated by regulating the HGF/c-met signaling Pathway.