OBJECTIVE To investigate the antidepressant effect of triptolide in chronically unpredictable stressed mice and its possible protective effect on brain derived neurotrophic factor(BDNF). METHODS One method was selected from 8 different stress methods each day,and the mice were treated with triptolide(20,40,80 and 160μg·kg-1)10 min before the stress method. A chroni?cally unpredictable stressed model was established and after 14 d stress experiment, the total distance in the locomotor activity and the immobility time in the force swimming test and tail test were observed respectively. Triptolide(20,40,80 and 160μg·kg-1)was given 10 min before the test. In addition, Western blot was used to analyze the expression of phosphorylated cAMP response element binding protein(p-CREB) and BDNF in the hippocampus and frontal cortex. RESULTS There was no effect on the locomotor activity in any group. Compared with the normal control group,the chronically unpre?dictable stressed group showed obvious depressive-like behavior,while the immobility time in the force swimming test decreased from(161 ± 18)s in chronically stressed group to(102 ± 14)s(P<0.05) and(83±14)s(P<0.01)when mice were ip given triptolide 80 and 160μg·kg-1, respectively,and(77± 11)s(P<0.01)in imipramine(IMI)hydrochloride group(10 mg?kg-1),and(96±9)s(P<0.01)in fluox?etine(FLU)group(10 mg?kg-1). The immobility time in the tail suspension test decreased from(128± 8)s in chronically stressed group to(93±9)s(P<0.05),(85±8)s(P<0.01)and(77±11)s(P<0.01)when mice were ip given triptolide 40,80 and 160μg · kg-1 respectively,and(64 ± 9)s(P<0.01)in IMI hydro?chloride 10 mg?kg-1 group,and(72±6)s(P<0.01)in FLU group(10 mg?kg-1). Moreover,the expression of p-CREB in the hippocampus and frontal cortex significantly increased in triptolide 80 and 160μg·kg-1 groups(P<0.05),so did the expression of BDNF in the hippocampus and frontal cortex in triptolide 80 and 160μg·kg-1 groups(P<0.05). CONCLUSION Triptolide can ameliorate the depressive-like behavior in chronically unpredictable stressed mice,which may be related to the cAMP-CREB-BDNF signal transduction cascades.

Objective To establish a luciferase labeled McA-RH7777 hepatoma rat model,which could be used for gross observation to further observe the effect of selective ligation of the portal vein and bile duct on tumor growth and metastasis.Methods The luciferase gene was transfected into rat McA-RH7777 hepatoma cells with pCDH-puromycin-CMV as the carrier,which were subcutaneously inoculated into Buffalo rats.Tumor pieces were then heterotransplanted into the left lateral lobe of the allogenic rat liver to observe the tumor growth in vivo.After the successful hepatoma modeling,the rats were randomly divided into three groups,namely the implanted portal vein group with combined portal vein and bile duct ligation,the implanted portal vein group with single portal vein ligation and sham operation group.The rats were executed at the 1 st week and 2nd week after ligation,and the livers were dissected to record the tumor growth and metastasis inside and outside the liver,respectively.Results The tumor formation rates of Buffalo rats after subcutaneous and intrahepatic implantation were both 100％.The fluorescence signal implanted into the liver lobe could be observed in vivo after the intrahepatic implantation of luciferase transfected Luc-McA-RH7777 at 2nd week,the range and intensity of which increased over time.Only local tumor growth could be found at the 4th week,without obvious intrahepatic and lung metastasis.However,both an increased in situ tumor volume and the pulmonary metastasis could be observed in the implanted portal vein group with combined portal vein and bile duct ligation at 2nd week after the ligation.Immunohistochemistry showed AFP positive immunoreactions in the vast majority of intrahepatic tumor cells and Luc positive immunoreactions in part of tumor cells.Conclusion Luc-McA-RH7777 cells could be used to establish the heptoma rat model and the in vivo analysis within the Buffalo rat liver demonstrated that the combined ligation of the portal vein and bile duct can accelerate the development and metastasis of liver cancer.

Objective To summarize the clinical experience of immunosuppressive therapy for recipients suffering from psoriasis after liver transplantation. Methods Five patients diagnosed with cirrhosis or hepatocellular carcinoma (HCC)complicated with psoriasis after liver transplantation were recruited in this clinical trial. All participants were positive for serum biomarkers of hepatitis B virus (HBV). Induction therapy was adopted before surgery. Immunosuppressive regime of tacrolimus (FK506),mycophenolate mofetil (MMF)and adrenal cortical hormone (hormone) was implemented early after surgery. The hormone use was terminated within 1 week. Three cases of cirrhosis complicated with HCC due to chronic HBV infection were gradually switched to sirolimus substitution treatment within 1 month after liver transplantation. Two patients with cirrhosis were administered with FK506 with or without MMF following liver transplantation. All patients received anti-HBV therapy. Baseline data,changes in psoriasis area and severity index (PASI)score and adjustment of postoperative immunosuppressive agents were analyzed. Results Five patients undergoing transplantation were followed up until the submission date with a mean duration of (8. 3 ±1 . 5 )years and survived. Compared with preoperative values,PASI score was significantly reduced at postoperative 6 months (P<0. 05 ). Two patients with cirrhosis had recurrent psoriasis at 2 years after liver transplantation. PASI score was significantly increased and steadily declined after sirolimus substitution therapy. These patients remained physically stable and did not progress at postoperative 3 years. Three patients suffering from cirrhosis complicated with HCC presented with no recurrence of psoriasis postoperatively. Conclusions Sirolimus-based immunosuppressive therapy can effectively control the progression of psoriasis in liver transplantation recipients. Anti-HBV treatment should be simultaneously implemented for HBV positive patients.