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目的:探究胆固醇对人半月板纤维软骨细胞基质合成及降解相关基因表达的影响及其机制。方法:获取关节镜手术患者半月板组织并提取纤维软骨细胞,分为对照组(正常细胞不做处理)、阳性对照组(白介素-1n β进行退行性病变造模)和15 μg/mL组(给予15 μg/mL浓度胆固醇处理细胞)、30 μg/mL组(给予30 μg/mL浓度胆固醇处理细胞)。番红O染色、n β-半乳糖苷酶染色和酶法试剂盒分别检测半月板细胞形态及总胆固醇(TCH)含量,免疫荧光和Western blot检测Ⅰ型胶原前体n α1(COL1A1)和Ⅱ型胶原前体n α1(COL2A1)的蛋白表达,RT-qPCR检测COL1A1、COL2A1、基质金属蛋白酶(MMP)3、MMP9、MMP13,以及胆固醇流出通路相关基因的mRNA表达,如肝脏X受体n α (LXRn α)、ATP结合盒转运蛋白A1(ABCA1)和ABCG1。n 结果:与对照组比较,阳性对照组的人半月板细胞TCH含量无显著变化,差异无统计学意义(n P>0.05);当给予胆固醇处理后,即15 μg/mL组和30 μg/mL组人半月板细胞TCH含量较对照组显著增加,差异均有统计学意义(n P<0.05)。与对照组相比,15 μg/mL组和30 μg/mL组LXRn α、ABCA1和ABCG1的mRNA表达降低,差异均有统计学意义(n P< 0.05)。与对照组相比,阳性对照组、15 μg/mL组和30 μg/mL组半月板细胞的密度降低、分布紊乱且细胞特征逐渐减弱,明显老化。与对照组相比,15 μg/mL组和30 μg/mL组可以降低半月板细胞COL1A1和COL2A1的mRNA表达,差异均有统计学意义(n P<0.05)。与对照组相比,15 μg/mL组和30 μg/mL组半月板细胞的MMP3、MMP9和MMP13的mRNA表达升高,差异均有统计学意义(n P0.05). The treatments with 15 and 30 μg/mL cholesterol resulted in significantly increased TCH contents in human meniscal fibrochondrocytes in the treatment groups (n P<0.05). Compared with the control group, the mRNA expression of LXRn α, ABCA1 and ABCG1 was significantly decreased in the treatment groups (n P<0.05), and the meniscal fibrochondrocytes in the positive group and the treatment groups presented with a lower density, chaotic distribution and obvious signs of degradation. Compared with the control groups, the mRNA expression of matrix synthesis genes (COL1A1 and COL2A1) in the meniscal fibrochondrocytes was significantly inhibited while the mRNA expression of matrix degradation metalloenzymes (MMP3, MMP9 and MMP13) was significantly promoted (n P<0.05).n Conclusion:Cholesterol may inhibit the cholesterol efflux pathways of meniscal fibrochondrocytes, and thus cause accumulation of cholesterol in the meniscal fibrochondrocytes, eventually leading to degeneration of meniscus.