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目的:研究甘草查尔酮A对大鼠骨关节炎的作用及其与p38-MAPK炎症信号通路的关系。方法:将雄性Wistar 大鼠160只采用区组随机化方法随机分为空白-未干预组，空白-干预组，关节炎-未干预组，关节炎-干预组，每组40只。关节炎组大鼠以单侧膝关节前交叉韧带切断术处理，空白组大鼠仅做皮肤切开缝合；甘草查尔酮A干预组大鼠予以10 μmol/L 甘草查尔酮A 1 mL 关节腔内注射，干预实施8周。8周后番红染色各组大鼠的软骨，并进行光镜下骨关节炎软组织病理（OARSI）评分；将软骨培养在5% 胎牛血清低糖细胞培养基内48 h，用化学显色法测定培养基一氧化氮（NO）、前列腺素En 2（PGEn 2）、硫酸化糖胺聚糖（sGAG）和二型胶原（Collagen Ⅱ）含量；以蛋白质印迹法检测大鼠软骨组织中p38、磷酸化的p38（p-p38）和基质金属蛋白酶（MMP）表达。n 结果:甘草查尔酮A干预的大鼠骨关节炎进展缓慢，关节炎-干预组OARSI 评分为（3.8±1.7）分，低于关节炎-未干预组的（9.7±1.2）分，差异有统计学意义（n P=0.006）；关节炎-干预组NO释放量为（77.84±17.65）μmol/mg，PGEn 2释放量为（6.78±1.76）ng/mg，sGAG丢失量为（89.78±9.76）μg/mg，Collagen Ⅱ丢失量为（1.78±0.76）μg/mg，分别显著低于关节炎-未干预组的（107.56±18.74）μmol/mg、（10.756±1.87）ng/mg、（125.75±8.87） μg/mg、（3.76±0.88）μg/mg，差异均有统计学意义（NO：n P=0.002；PGEn 2：n P<0.001；sGAG：n P<0.001；Collagen Ⅱ：n P<0.001）。蛋白质印迹结果表明，关节炎-干预组p38相对表达量（3 454±421）、p-p38相对表达量（2072±175）、p-p38占总p38比值为（0.65±0.14）、MMP相对表达量（1 776±765），与关节炎-未干预组p38相对表达量（5 322±323）、p-p38相对表达量（4 257±184），p-p38占总p38比值（0.89±0.11）、MMP相对表达量（3 865±874）相比均减少，且差异有统计学意义（p38：n P<0.001；p-p38：n P<0.001；p-p38/p38：n P=0.002；MMP：n P=0.001）。n 结论:甘草查尔酮A可以通过抑制炎性反应和和抑制软骨基质降解来延缓实验骨关节炎大鼠的骨关节炎进展，p38-MAPK信号通路可能参与了其中的调控过程。“,”Objective:To investigate the effect of licochalcone A on osteoarthritis in rats and its relationship with p38-MAPK inflammatory signaling pathway.Methods:A total of 160 male Wistar rats were randomly divided into blank non-intervention, blank intervention, arthritis non- intervention and arthritis intervention groups with 40 rats in each group. Rats in the arthritis groups were subjected to unilateral anterior cruciate ligament transection, while rats in the blank groups were only subjected to skin incision and suture. Rats in the intervention groups were treated by intra-articular injection of 1 mL 10 μmol/L licochalcone A for 8 successive weeks. Eight weeks later, the cartilage of rats in each group was stained with safranin, and osteoarthritis soft tissue was scored according to Osteoarthritis Research Society International guideline under the optical microscope. The cartilage was cultured in low glucose cell culture medium supplemented with 5% fetal bovine serum for 48 hours. The contents of nitric oxide, prostaglandin En 2, sulfated glycosaminoglycan and collagen II in the medium were determined by the chemiluminescence reaction method. The expression levels of p38, phosphorylated p38 (p-p38) and matrix metalloproteinase in cartilage tissue were detected by western blot assay.n Results:The progress of osteoarthritis in rats treated with licochalcone A was slow. The Osteoarthritis Research Society International score in the arthritis intervention group was significantly lower than that in the arthritis non-intervention group [(3.8 ± 1.7) points n vs. (9.7 ± 1.2) points, n P = 0.0064]. The contents of nitric oxide, prostaglandin En 2, sulfated glycosaminoglycan, and collagen II in the arthritis intervention group were (77.84 ± 17.65) μmol/mg and (6.78 ± 1.76) ng/mg, (89.78 ± 9.76) μg/mg, and (1.78 ± 0.76) μg/mg, respectively, which were significantly lower than those in the arthritis non-intervention group [(107.56 ± 18.74) μmol/mg, (10.756 ± 1.87) ng/mg, (125.75 ± 8.87) μg/mg, (3.76 ± 0.88) μg/mg, (NO: n P = 0.002; PGEn 2: n P < 0.001; sGAG: n P < 0.001; Collagen II: n P < 0.001). Western blot assay results revealed that the relative expression of p38, p-p38, p-p38 to total p38 ratio, matrix metalloproteinase in the arthritis intervention group were (3 454 ± 421), (2 072 ± 175), (0.65 ± 0.14 )and (1 776 ± 765), respectively, which were significantly lower than those in the arthritis non-intervention group (5 322 ± 323), (4 257 ± 184), (0.89 ± 0.11), (3 865 ± 874)( p38: n P < 0.001; p-p38: n P < 0.001; p-p38/p38: n P = 0.002; MMP: n P = 0.001).n Conclusion:Licochalcone A can delay the progression of osteoarthritis in rats with osteoarthritis through inhibiting inflammatory reaction and cartilage matrix degradation, and p38-MAPK signaling pathway may be involved in the regulation process.