Effect of WeiJia on carbon tetrachloride induced chronic liver injury

AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： normal control group （Group A）, CCh induced liver injury control group （Group B） and CCI4 induction with WeiJia treatment group （Group C）. Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCh in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of Wei.lia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week （4 male, 3 female）, and eighth week （4 male, 3 female） respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid （HA）, type Ⅳ collagen （CIV）, γ-glutamyl transferase （γ-GT）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined. Alpha smooth muscle actin （α-SMA） and proliferating cell nuclear antigen （PCNA） immunohistochemistry were also performed. RESULTS： CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L （P〈0.01）, 57±21 μg/L （P〈0.01）, 47±10 U/L （P〈0.01）, 139±13 U/L （P〈0.05） and 52±21 U/L （P〉0.05） respectively, similar to normal control group （Group A）, but significantly different from CCh induced liver injury control group （Group B）. An increase in PCNA and decrease in α-SMA expression level was also observed. CONCLUSION： WeiJia could improve liver function and reduce liver fibrosis which might be through the inhibition of stellate cell activity.

Imipramine Inhibits Adipogenic Differentiation in Both 3T3-L1 Preadioocvtes and Mouse Marrow Stromal Cells

Imipramine （IM） has been widely used clinically for the treatment of mental disorders. Its actions on tissues or organs other than the nervous system also need to be understood for its proper clinical use. In this study, the effects of IM on adipogenic differentiation in both 3T3-L1 preadipocytes and mouse marrow stromal cells （MSCs） were investigated. The results showed that fewer adipocytic cells were developed from 3T3-L1 preadipocytes in the presence of 0.001 to 1 μmol/L of IM as compared to control. Similar inhibitory effect was also observed in mouse MSCs. The decrease in the formation of adipocytes was accompanied with significant down-regulation at mRNA expression of the early adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 （PPARγ2）. Western blot analysis further revealed that the protein expression of PPARγ2 was reduced markedly in ceils treated with IM at concentrations of 0.01, 0.1 and 1 μmol/L, suggesting that the suppression on PPAR72 was involved in IM＇s inhibition on MSCs adipogenesis. Moreover, IM at the above concentrations could stimulate the mRNA expression of β2-adrenergic receptor （AR） and β3-AR, which implicated that the effect of IM on adipogenic differentiation was partially mediated by β-ARs. Our results demonstrated for the first time that the conventional antidepressive imipramine exerts accompanied inhibitory effect on adipocyte formation, which may have possible clinical implications.