Ciliary neurotrophic factor (CNTF) analogues were reported to ameliorate fatty liver in db/db or high-fat diet-fed mice. It is generally thought that CNTF exerts its actions centrally. The aim of this study was to investigate whether peripheral effects of CNTF analogues are involved in the therapeutic effect on high fat-induced hepatic steatosis. The rat model of fatty liver was induced by a high-fat diet (HFD) for 12 weeks. In the next 2 weeks, rats were fed the HFD along with subcutaneous injection of vehicle or mutant recombinant human CNTF (rhmCNTF 0.05-0.2 mg/kg per day). Steatotic HepG2 cells were induced by 50% fetal bovine serum (FBS) for 48 hours, and then treated with rhmCNTF for 24 hours. The results showed that after rhmCNTF treatment, hepatic triglyceride (TG) accumulation was attenuated both in vivo and in vitro. RhmCNTF increased protein expression of CPT-1 and PPARα, and decreased SREBP-1c, FAS and SCD-1 in steatotic HepG2 cells. But the production of nitric oxide and 8-isoPGF2α in steatotic HepG2 cells was not affected by rhmCNTF. These results suggest that rhmCNTF has a peripheral effect that alleviates fat-induced hepatic steatosis.

The aim of this study was to elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE) on recurrent ulcerative colitis (UC) in rats. GSPE in doses of 100, 200, and 400mg/kg were intragastrically administered per day for 7 days after recurrent colitis was twice-induced by TNBS. The levels of GSH, as well as the activity of GSH-Px and SOD in colon tissues were measured by biochemical methods. The expression levels of tumor necrosis factor-α (TNF-α) and the nuclear translocation levels of nuclear factor-kappa B (NF-κB) in the colon tissues were measured by enzyme-linked immunosorbent assay methods. Western blotting analysis was used to determine the protein expression levels of inhibitory kappa B-alpha (IκBα), inhibitor kappa B kinase (IKKα/β), phosphorylated IκBα and phosphorylated IKKα/β. GSPE treatment was associated with a remarkable increased the activity of GSH-Px and SOD with GSH levels in TNBS-induced recurrent colitis rats as compared to the model group. GSPE also significantly reduced the expression levels of TNF-α, p-IKKα/β, p-IκBα and the translocation of NF-κB in the colon mucosa. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response and promoting damaged tissue repair to improve colonic oxidative stress. Moreover, GSPE inhibited the TNBS-induced inflammatory of recurrent colitis though blocking NF-κB signaling pathways.

Metabolic syndrome (MS) is highly prevalent in developed countries and becoming a serious worldwide public health issue. In this study, we established a MS model by feeding male C57BL/6J mice with a high-fat diet (10%) for 18.5 weeks, studied the therapeutic effects of a recombinant mutant of the human ciliary neurotrophic factor (rhmCNTF) 0.1 (C-0.1) or 0.3 (C-0.3) mg x kg(-1) per day subcutaneously or pair feeding (PF, which mice were restricted to the same amount of food as eaten by C-0.3 treated mice) in MS mice. After 10 days treatment, rhmCNTF reduced obesity related indices, ameliorated glucose and lipid metabolism abnormality, and enhanced insulin sensitivity. In addition, liver function and antioxidant ability of MS mice were improved by rhmCNTF. Pair feeding revealed the same effects as C-0.3 on obesity related indices and insulin sensitivity, but aggravated hepatic steatosis and hepatic function. The results suggest that rhmCNTF could serve as an effective therapeutic agent for MS and related diseases.

Objective To establish a recurrent colitis model in rats.Methods Wistar male rats were randomized divided into four groups:normal control group,acute colitis group,spontaneous healing group and recurrent colitis group.Recurrent colitis was induced in rats by rectal administration of 80 mg/kg 2,4,6-trinitrobenzenesulfonic acid solution(TNBS) dissolved in 50%ethanol, and then the rats were instilled again with 30 mg/kg TNBS into the colon on the 16th day after the first induction ulcerative colitis.All the rats were sacrificed 7 days after second induced ulcerative colitis by TNBS.Macroscopical and microscopical damage scores and myeloperoxidase(MPO) activity were assessed,and the colonic injury and inflammation were evaluated respectively.Results Compared with normal control group,acute colitis group and spontaneous healing group, macroscopical and microscopical damage scores and MPO activity were notably increased in the recurrent colitis group.Conclusion A recurrent colitis model in rats has been established.This twice-induced animal colitis by TNBS is more similar to human inflammatory colitis which can be used in the study of the remission-period recurrence.

Aim To study the characteristics of mouse metabolic syndrome(MS) model induced by high-fat diet and the effect of sibutramine on MS mice.Methods 9-week-old male C57BL/6J mice,fed with high-fat diet(10% lard,2% cholesterol,and 0.4% sodium cholate in basic diet) for 18.5 weeks were treated with saline or sibutramine 8 mg·kg-1 for 10 days.The body weight,wet weight of visceral fat and liver,liver free fatty acid(FFA) content,serum level of lipid,glucose and insulin were examined at the end of the treatment.Results The excessive fat in abdominal cavity was accumulated in MS mice accompanied with hypercholesterolemia,hyperglycemia,hyperinsulinemia,and insulin resistance.In addition,liver weight and grade of hepatic steatosis increased significantly in MS mice.These symptoms in MS mice were similar to those in human beings.After 10 days treatment,sibutramine reduced the obesity related indices,ameliorated glucose and lipid metabolism abnormality,and enhanced insulin sensitivity,but it increased liver FFA content and had no obvious effect on liver weight and hepatic steatosis in MS mice.Conclusions MS model can be induced in C57BL/6J mice by long-term feeding with high-fat diet and sibutramine has a certain therapeutic effect on MS in mice.