Effect of Gubi prescription on caveolin-1 expression and phosphoinositide 3 kinase/protein kinase B and Fas signal pathways in rats with knee osteoarthritis.

OBJECTIVE To investigate the effects of Gubi prescription on the expression of caveolin-1, and the phosphoinositide 3 kinase/protein kinase B (PI3K/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. mRNA 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 siRNA, 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 medium-dose 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 PI3K/Akt and Fas signal pathways and inhibited the overexpression of caveolin-1 in rat chondrocytes.