【摘要】 目的观察不同剂量姜黄素对注射聚乙烯磨损颗粒小鼠air-pouch模型囊壁组织MMP-2、MMP-9表达的影响,并探讨姜黄素干预磨损颗粒诱发炎性反应的作用机制。方法取健康昆明系小鼠72只,参照Yang等方法构建air-pouch动物模型,于背部囊腔中注入3mL浓度为1×108个/mL高分子聚乙烯颗粒悬液。动物模型随机分为3组(n=24),对照组(A组):生理盐水灌胃0.6mL/d;低剂量实验组(B组):浓度为1.6mg/mL姜黄素溶液灌胃0.6mL/d;高剂量实验组(C组):浓度为3.2mg/mL姜黄素溶液灌胃0.6mL/d。术后观察动物一般情况,于给药后3、7及14d,每组取8只小鼠背部囊壁组织行大体、组织学观察及免疫组织化学、RT-PCR、Westernblot检测。结果各组小鼠均存活至实验完成。各组小鼠背部皮下均可见一白色的囊腔组织,各时间点A组囊腔直径大于B、C组,C组小于B组。镜下观察A组炎性反应强于B、C组,7、14d时C组明显弱于B组。给药后3d,B、C组囊壁组织中MMP-2、MMP-9表达与A组差异无统计学意义(P>0.05);7、14d时差异有统计学意义(P<0.05)。给药后7dC组MMP-2表达与B组比较差异无统计学意义(P>0.05),14d时两者差异有统计学意义(P<0.05);7、14d两组MMP-9表达差异有统计学意义(P<0.05)。给药后NF-κBP65因子的核转位受到明显抑制,在7、14d时3组间差异具有统计学意义(P<0.05),3d时差异无统计学意义(P>0.05)。结论聚乙烯磨损颗粒可刺激囊壁组织MMP-2、MMP-9的表达。姜黄素可以抑制air-pouch动物模型囊壁组织中MMP-2、MMP-9的表达,MMP-2、MMP-9表达可能受NF-κB活化的调节。更多还原

【Abstract】 Objective To observe the e ect of di erent 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 in ammatory 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 × 108 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 signi cantly less than group B. Microscope observation showed that in ammatory 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 signi cant di erence 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 signi cant di erences were evident at 3 days (P > 0.05). There was no signi cant di erence between group B and group C in MMP-2 expression at 7 days after curcumin delivery (P > 0.05), and signi cant di erence was evident at 14 days (P < 0.05). There was signi cant di erence bewteen group B and group C in MMP-9 expression at 7 and 14days after curcumin delivery (P < 0.05). Nuclear translocation of NF-κB P65 was inhibited remarkably after curcumin delivery, and there were signi cant di erences among three groups at 7 and 14 days (P < 0.05), and no signi cant di erences 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-κB.更多还原