姜黄素抑制聚乙烯磨损颗粒诱导MMP-2和MMP-9表达及机制的研究

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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。 Objective To observe the effects of different doses of curcumin on the expression of MMP-2 and MMP-9 in the cystic wall of mouse air-pouch model injected with polyethylene wear particles, and to explore the mechanism of the curcumin-induced inflammatory response induced by wear particles. Methods A total of 72 healthy Kunming mice were selected and an air-pouch animal model was constructed by Yang et al. A 3 mL high-molecular-weight polyethylene suspension was injected into the dorsal cyst. The animal models were randomly divided into 3 groups (n=24). The control group (group A): normal saline administered intragastrically at 0.6 mL/d; the low-dose experimental group (group B) at a concentration of 1.6 mg/mL curcumin solution was intragastrically administered 0.6 mL/d; high-dose experimental group (C group): The concentration of 3.2mg/mL curcumin solution was intragastrically administered with 0.6mL/d. The general condition of the animals was observed after surgery. On the 3rd, 7th and 14th days after administration, the dorsal cyst wall tissue of 8 mice in each group was subjected to gross and histological observation, and immunohistochemistry, RT-PCR and Western blot were performed. Results All mice survived until the experiment was completed. A white cyst tissue was found subcutaneously in the back of each group. The cystic diameter of group A was greater than that of group B and C at each time point, and group C was smaller than group B. The inflammatory response of group A was stronger than that of group B and C. The group C was significantly weaker than group B at 7 and 14 days. At 3 days after administration, the expression of MMP-2 and MMP-9 in cystic wall tissue of group B and C was not significantly different from that in group A (P>0.05). There was a significant difference between days 7 and 14 (P<0.05). There was no significant difference in the expression of MMP-2 between group C and group B at 7 days after administration (P>0.05). There was a significant difference between group C and group B on day 14 (P<0.05). There was a difference in the expression of MMP-9 between groups 7 and 14d. Statistical significance (P<0.05). The nuclear translocation of NF-κB P65 was significantly inhibited after administration, and there was a statistically significant difference between the 3 groups at 7 and 14 days (P<0.05). There was no significant difference at 3 days (P>0.05). Conclusion Polyethylene wear particles can stimulate the expression of MMP-2 and MMP-9 in cyst wall tissue. Curcumin can inhibit the expression of MMP-2 and MMP-9 in the air-pouch animal model. The expression of MMP-2 and MMP-9 may be regulated by NF-κB activation.
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