Study on the efficacy and mechanism of triptolide on treating TNF transgenic mice with rheumatoid arthritis

Abstract

ObjectiveTo discuss the curative effect and security of triptolide (TPL) on TNF transgenic (TNF-Tg) mice with rheumatoid arthritis (RA), and to explore the mechanism primarily. Method40 TNF-Tg RA mice were randomlydivided into five groups averagely: the control group, low-dose group (3.3 μg/kg/d TPL), middle-dose group (10 μg/kg/d TPL), high-dose group (33 μg/kg/d TPL) and MTX group (0.1 mg/kg/d MTX). Mice were administrated five days a week for six weeks. The arthritis deformation index, arthritis detumescencepercentage and the level of inflammatory factor in each group were recorded during theadministration. After administration, body weight, liver and renal function indexes, the apoptosis rates of osteoclast precursors (OCP), T and B lymphocytes in the peripheral blood and the number of osteoclast (OC) were detected and compared. μCT scanning and HE staining methods were taken to observethebone histomorphometry and bony erosion. ResultAfter administration, the arthritis deformation indexes were lower and arthritis detumescence percentageswere higher in TPL groups thanthe control group (P < 0.05), and the arthritis detumescence percentage in the high-dose group was higher than the MTX group (P < 0.05). The liver function index ALT increased after administrationin the high-dose group but was lower than that in the MTX group (P < 0.05). The level of IL-1α, IL-1β, and TNF-α decreased in the TPL groups and MTX group after administration;The apoptosis rates of OCP and T lymphocytes in middle and high dose TPL groups and MTX group were higher than other groups, and that in the high-dose group was higher than the MTX group (P < 0.05). Compared with the other groups, the bony erosion degree was lower and the number of OC was less and the parameters of bone histomorphometry were better in the high-dose group. ConclusionTPL could improvearthritic of TNF-Tg mice by decreasing the levels of pro-inflammatory cytokines, promoting the apoptosis of OCP, inhibiting the generation of OC and bone resorption. There was some toxic and side effect on liver for high-dose TPL which was weaker than the MTX.