Therapeutic Mechanism of Simvastatin on Collagen Induced Arthritis in Rats / 天津医药

ABSTRACT

Objective To evaluate therapeutic effects of simvastatin on serum expressions of cytokines and synovial tissue aspartic protease-3 (Caspase-3) in collagen induced arthritis (CIA) in rats, and the mechanism thereof. Methods The rat model of CIA was established by injecting bovine Ⅱ collagen. Sixteen model rats were randomly divided into two groupsCIA model group (sterile water 5 mL·kg-1·d-1 by gavage) and simvastatin group (2.0 mg·kg-1·d-1 by gavage). Seven normal rats were included in control group (sterile water 5 mL·kg-1·d-1 by gavage). The arthritis index (AI) and hind paw vol-umes were recorded once a week. The serum levels of cytokine, tumor necrosis factor (TNF)-αand interleukin (IL)-6 were measured by ELISA 42 days after the initial immunization. The expression of Caspase-3 in ankle synovial tissue was detect-ed by immunohistochemical method, and pathological results of HE staining in rat ankle were compared between three groups. Results Values of AI were decreased on the 24-d of the initial immunization in simvastatin group and CIA model group, which was significantly decreased on the 35-d of the initial immunization in simvastatin group than that of CIA model group (P＜0.05). The values of hind paw volumes were decreased on the 14-d of the initial immunization in simvastatin group and CIA model group, which was still significantly higher than those of control group (P＜0.05). The values of hind paw volumes were decreased on the 35-d and 42-d of the initial immunization in simvastatin group than those of CIA model group (P＜0.05). The serum levels of TNF-αand IL-6 on the 42-d of the initial immunization were significantly lower in simvastatin group than those of CIA model group, but which were significantly higher than those of control group ( P＜0.05). There were more synovial hyperplasia in simvastatin group than those of CIA model group. Only a small amount of inflamma-tory cell infiltration was found in simvastatin group. The expression of Caspase-3 was significantly higher in simvastatin group than that of CIA model group. Conclusion Simvastatin can significantly inhibit the serum levels of TNF-αand IL-6 in CIA model rats, and can up-regulate the expression of Caspase-3 in ankle of model rats.