Abstract: OBJECTIVE: To investigate the effects of Gubi prescription on the expression of caveolin-1, and the phosphoinositide 3 kinase/protein kinase B(PI3 K/Akt) and Fas signal pathways in rats with knee osteoarthritis(KOA).METHODS: Forty KOA model rats were established using a modification of Hulth's method. Rats were divided into five groups by the random number method: model, positive drug(Vicolli group), and high-, medium-, and low-dose Gubi prescription groups(n = 8/group). In the sham surgery group(n = 8), only anterior and posterior cruciate ligaments of rats were exposed during surgery. A normal group(n = 8) consisted of rats with no treatment. Rats were intragastrically administered corresponding drugs once every day for eight consecutive weeks. Then, rat synovial membranes were extracted and histomorphological changes were recorded. m RNA expression was measured by q-PCR.Serum superoxide dismutase(SOD), malondialdehyde(MDA), nitric oxide(NO), and interleukin 1β(IL-1β) levels were measured. Western blotting determined the effects of Gubi prescription on protein expressions of caveolin-1, Bax, Bcl-2, Fas, and caspase-3 in chondrocytes from KOA rats. The knee cartilage of rats was excised and cultured under aseptic conditions. After coincubation of chondrocytes with Gubi prescription-containing serum, IL-1β, and si RNA, Western blotting was used to determine the protein expressions of caveolin-1, Bax, Bcl-2, Fas, and caspase-3.RESULTS: The morphological score of the articular synovium in the model group was significantly higher than in the normal group(P < 0.01). The morphological score in the high-and mediumdose Gubi prescription groups was lower than in the model group(P < 0.05). Chondrocytes from the decoction-containing serum group had a lower expression of Bax(P < 0.05), and higher expressions of Bcl-2(P < 0.05) and caspase-3(P < 0.05) compared with the model group. Chondrocytes in the decoction-containing serum group had higher expressions of Bax and Bcl-2(P < 0.01) and lower expressions of caveolin-1 and Fas(P < 0.05) compared with the model group. Compared with the model group, Bax and caspase-3 expressions were reduced in the chondrocytes of all three Gubi prescription groups(P < 0.05) whereas Bcl-2 expression was increased(P < 0.05). Compared with the model group, the expressions of caveolin-1 and Fas(P < 0.05) were reduced in groups that received high-and medium-doses of Gubi prescription. Gubi prescription increased the serum level of SOD and significantly reduced those of MDA, NO and IL-1β(P < 0.05).CONCLUSION: Gubi prescription suppressed the chondrocyte-related PI3 K/Akt and Fas signal pathways and inhibited the overexpression of caveolin-1 in rat chondrocytes.

Key words: Osteoarthritis,knee, Caveolin 1, Phosphatidylinositol 3-kinase, Superoxide dismutase, Malondialdehyde, Nitric oxide, Interleukin-1beta, Gubi prescription