[Inhibitory effect of curcumin on MMP-2 and MMP-9 expression induced by polyethylene wear particles and its mechanism].

ABSTRACT

OBJECTIVE: To observe the effect of different dosage of curcumin on expression of MMP-2 and MMP-9 in the tissue of cystiform in air-pouch mouse models after the injection of polyethylene wear particles, and to investigate its mechanism of intervening inflammatory response induced by wear particles. METHODS: Seventy-two kunming strain mice were used to establish air-pouch animal models by referring to the method of Yang et al. and injecting 3 mL suspension of ultra-high molecular weight polyethylene wear particles (concentration 1 x 10(8) cells/mL) into dorsal cyst cavity. Then the animals were randomized into 3 groups (n = 24 per group) group A (control group), 0.6 mL/day normal saline by gavage; group B (low-dosage experimental group), 0.6 mL/day curcumin solution at a concentration of 1.6 mg/mL by gavage; group C (high-dosage experimental group), 0.6 mL/day curcumin solution at a concentration of 3.2 mg/mL by gavage. General condition of the animals was observed after operation. The mice were killed 3, 7 and 14 days after operation (8 mice per group at a time), the tissue of cystiform was harvested to receive gross, histology and immunohistochemistry observation, as well as RT-PCR and Western blot detection. RESULTS: All mice survived till the end of experiment. White cystiform tissue was evident on the back of mice subcutaneously in each group. For diameter of the cyst cavity at each time point, group A was obviously greater than groups B and C, and group C was significantly less than group B. Microscope observation showed that inflammatory response in group A was stronger than that of groups B and C, and group C was obviously less than group B at 7 and 14 days. There was a significant difference between groups B and C and group A in terms of MMP-2 and MMP-9 expression at 7 and 14 days after curcumin delivery (P < 0.05), and no significant differences were evident at 3 days (P > 0.05). There was no significant difference between group B and group C in MMP-2 expression at 7 days after curcumin delivery (P > 0.05), and significant difference was evident at 14 days (P < 0.05). There was significant difference bewteen group B and group C in MMP-9 expression at 7 and 14 days after curcumin delivery (P < 0.05). Nuclear translocation of NF-kappaB P65 was inhibited remarkably after curcumin delivery, and there were significant differences among three groups at 7 and 14 days (P < 0.05), and no significant differences were evident at 3 days (P > 0.05). CONCLUSION: Ultra-high molecular weight polyethylene wear particles can stimulate expression of MMP-2 and MMP-9 in cystiform tissue. Curcumin can restrain expression of MMP-2 and MMP-9 in cystiform tissue of air-pouch animal models, and expression of MMP-2 and MMP-9 may be regulated by the activation of NF-kappaB.