| Objective To clarify the feasibility that the senescence-accelerated mouse Prone8(SAMP8)is a valuable animal model for the study of liver senescence,and then investigate the effect of Ginsenoside Rg1 and Rb1 on liver senescence and its possible mechanism.Methods Male SAMP8 mice at an age of 3 months were chosen as research objects,and the same age SAMR1(senescence-accelerated mouse Resistantl)mice with a normal aging process as control.Mice were randomly devided into eight groups(eight mice in each group):SAMR1 group,SAMP8 group,Ginsenoside Rg1 groups(2.5,5,10mg/kg/d)and Ginsenoside Rb1 groups(2.5,5,10 mg/kg/d). SAMP8 mice in ginsenosides groups were injected with different dose of Rg1 or Rb1 intraperitoneally and equal volume of normal saline was given to SAMR1 and SAMP8 groups once a day continuously for 3 months.Histopathological changes in the liver of SAMR1 and SAMP8 mice were observed under light microscope. Senescence-associatedβ-galactosidase activity was measured with histochemical staining,and the activities of SOD,CAT,GSH-PX and the level of MDA in liver tissue homogenates were examined by chemical colorimetry to make sure feasibility that the SAMP8 is an ideal animal model for the study of liver senescence.Simultaneously we observed the dose-dependent protective effect of Ginsenoside Rg1 and Rb1 in liver senescence.Furthermore,we detected the expression and distribution of heme oxygenase-l(HO-1)in liver with immunohistochemistry staining and the level of mRNA of HO-1 with reverse transcription polymerase chain reaction(RT-PCR)in order to approach the possible mechanism of the effect of Ginsenoside Rg1 and Rb1 at aging liver. Results Compared with SAMR1 group,the SAMP8 mice exhibited general signs of aging,which included ruffled and dull coat,loss of hair,inflammation in the periorbital areas,abnormal curvature of the spine and slow action.The liver degeneration of SAMP8 mice was observed by microscopy,such as extensive fatty degeneration,focal necrosis of hepatocytes and inflammatory cells infiltration. Simultaneously positive staining for Senescence-associatedβ-galactosidase were widely found(P＜0.001).In addition,the activities of SOD,CAT,GSH-PX in liver tissue homogenates decreased(SOD P＜0.001,CAT P＜0.01,GSH-PX P＜0.05) and the level of MDA increased(P＜0.001)markedly,accompanied with the significant increases in the expression of HO-1 protein(P＜0.001)and mRNA(P＜0.01).HO-1 expression was restricted to some cells in hepatic sinusoid of SAMR1 mice,while it was identified intensively in hepatocytes of SAMP8 mice.Compared with SAMP8 group,Ginsenoside Rg1 or Rb1 could improve all senescent indicators as mentioned above to some degree as following:The Ginsenoside Rg1 and Rb1 groups treated with the dosage of 10mg/kg/d showed the most effective protection(Rg1 P＜0.001,Rb1 P＜0.05)on the pathological changes and SA-β-galactosidase activity.The activities of SOD,CAT,GSH-PX were higher and the level of MDA was lower significantly in Ginsenoside groups than in SAMP8 group.But the differrences are not significant between groups of different dosage. Meanwhile,the expression of HO-1 protein and mRNA were reduced remarkably in the liver of ginsenoside groups,especially in the Rg1 10mg/kg/d(P＜0.01)or Rb15mg/kg/d and 10mg/kg/d(P＜0.05)groups.Conclusion Ginsenoside Rg1 and Rb1 can delay liver senescence in SAMP8 mice.This effect may be due to improvement of antioxidase activities,inhibition of lipid peroxidation and inhibition of the expression of HO-1 in the liver. |
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