Curcumin Inhibit The Expression Of EMMPRIN,MMP-2,MMP-9 Induced By Ultra-high-molecular-weight Polyethylene Particles

Objective To observe the effect of curcumin on the expression of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9(MMP-9) induced by ultra-high- molecular-weight polyethylene (UHMWPE) wear particles, investigating possible mechanism involved in it, providing proof to the using of curcumin in the aseptic loosening therapyMethods UHMWPE wear debris were less than 10μm in diameter, which are produced in vitro. UHMWPE wear particles combine with phosphate buffered solution,which concentration is 1×108per mL, curcumin combine with physiological saline to the solution which concentration is 1.6 or 3.2mg/ml.Using a murine air pouch model of inflammation introduced by Yang, 72 KunMin mice were divided into 3 groups (24 per group) in the present study. The air pouches were injected with 3ml of UHMWPE suspension, Experiment animal were injected 50mg/ml or 100 mg/ml curcumin solution per day by stomach ,control group were injected the same volume saline,the situation of animal were observed after operation. All animals were sacrificed respectively at 3, 7, 14 d after the curcumin given, the inflammation of the wall of murine were observed by microscope, RT-PCR and Immunohistochemistry method was applied to detect the gene and protein expression of EMMPRIN,MMP-2,MMP-9 in the pouches. The expression of NF-κB in the nuclear was assayed by western blotResults All the experiment mice alive, there is a wall in the Subcutaneous of the back of mice ,the diameter of the wall of the control group is bigger than experiment group, group C is smaller than group B,the inflammation of control group is more serious and group B is more serious than group C, the number of inflammation cell in group A is more than group B,groupC,and group C is lesser than group B(P<0.05) at 7 days, the gene expression and positive cell rate of MMP-2,MMP-9 in all experiment group was reduced ,but expression of EMMPRIN is not (P<0.05) at 7 days; the gene expression and positive cell rate of EMMPRIN,MMP-2,MMP-9 in experiment group deal with curcumin was significantly lower than that in control group at 14d ( P < 0.05),but it is not at day 3( P >0.05) , the gene expression and positive cell rate of MMP-9 in group C is lower than group B (P<0.05),but the expression of EMMPRIN,MMP-2 in group C is not different from group B (P>0.05) at day 7,gene expression and positive cell rate of MMP-9 in group C is much lower than group B (P<0.01) and the gene expression and positive cell rate of EMMPRIN in group C is different from group B(P<0.05) at day 14, but it is not for MMP-2(P>0.05),the expression of NF-κBP65 was supressed significantly,NF-κBP65 in experiment group with curcumin was also lower than that in control group at day 7,14 (P < 0.05),and group C is lesser than group B at day 7,14 (P < 0.05) . but the expression is different with groups at day 3 (P >0.05).Conclusions This animal model can simulate the microenviroment of lossening arthroplasty,UHMWPE particles may result in EMMPRIN,MMP-2,MMP-9 expression at different time, the expression increased with time in two weeks. In addition, Curcumin can attenuates EMMPRIN,MMP-2,MMP-9 expression in air-pouch animal model, high dose curcumin suppressed the expression of EMMPRIN,MMP-9 more effective than low dose,but the suppression of MMP-2 is not relative with dose. Curcumin regulate the the expression of EMMPRIN ,MMP-2,MMP-9 may relative with the expression of NF-κB .