【摘要】 目的：观察活络骨康丸对兔激素性股骨头坏死（SONFH）的防治作用，探究其作用机制。方法：选取48只普通级新西兰兔，随机分为6组（每组各8只）：空白组、模型组、活络骨康丸低剂量组、活络骨康丸中剂量组、活络骨康丸高剂量组和阳性药物组。通过异体血清联合激素诱导股骨头坏死模型，预防性给予各组实验兔治疗药物6周，活络骨康丸低、中、高剂量组分别用低、中、高剂量活络骨康丸悬浊液灌胃治疗，阳性药物组用普伐他汀药液灌胃治疗。治疗结束后，MRI检测髋关节影像学改变，苏木精-伊红染色（HE）切片观察组织形态学病理变化，测定血清总胆固醇（CHO）、高密度脂蛋白胆固醇（HDL）和低密度脂蛋白胆固醇（LDL）水平，ELISA检测血清中细胞因子TNF-α、IL-1β、IL-6、IL-10和IL-4水平，RT-qPCR检测股骨头组织中过氧化物酶体增殖物激活受体γ（PPARγ）和诱导型一氧化氮合酶（iNOS）的mRNA表达水平，Western Blot检测股骨头组织中PPARγ、CCAAT/增强子结合蛋白α（C/EBPα）和iNOS蛋白表达水平。结果：MRI扫描显示模型组T₂WI可见股骨头软骨下骨区域表现出低信号强度的带状线，空白组、活络骨康丸低、中、高剂量组和阳性药物组未见明显异常。病理切片显示活络骨康丸低、中、高剂量组和阳性药物组较之模型组坏死灶减少，空骨陷窝率低、骨小梁面积升高，差异有统计学意义（P<0.05）。与模型组相比，活络骨康丸中、高剂量组血清总胆固醇、低密度脂蛋白胆固醇下降，高密度脂蛋白胆固醇升高，差异有统计学意义（P<0.05）；血清TNF-α、IL-1β和IL-6显著降低，IL-10和IL-4升高，差异有统计学意义（P<0.05）;PPARγ和iNOS mRNA的表达水平下降，差异有统计学意义（P<0.05）;PPARγ、C/EBPα和iNOS蛋白表达水平降低，差异有统计学意义（P<0.001）。结论：活络骨康丸可通过抑制PPARγ通路，纠正脂代谢的失衡，维持骨稳态，同时能够抑制激素性股骨头坏死中免疫因子介导的慢性炎症，达到防治激素性股骨头坏死的治疗目的。更多还原

【Abstract】 Objective:To investigate the therapeutic and preventive effects of Huoluogukang pill on steroid-induced osteonecrosis of the femoral head（SONFH）in rabbits and explore its mechanisms.Methods:48 New Zealand rabbits were randomly divided into 6 groups（n=8 per group）:blank group,model group,low-dose Huoluogukang group,medium-dose Huoluogukang group,high-dose Huoluogukang group,and positive drug group.SONFH models were induced by heterologous serum combined with hormone injections.lowdose,medium-dose,and high-dose Huoluogukang suspensions were given via gavage to the respective groups,while the positive drug group received pravastatin sodium solution.Post-treatment evaluations included MRI for hip joint imaging,hematoxylin-eosin（HE）staining for histopathological analysis,automatic biochemical analyzer for serum total cholesterol（CHO）,high-density lipoprotein cholesterol（HDL）,and low-density lipoprotein cholesterol（LDL）,ELISA for serum cytokines（TNF-α,IL-1β,IL-6,IL-10,IL-4）,RT-qPCR for mRNA expression of PPARγand iNOS in femoral head tissue,and Western Blot for PPARγ,C/EBPα,and iNOS protein expression.Results:MRI scans revealed that the model group exhibited low-signal-intensity banded lines in the subchondral bone region of the femoral head on T₂ WI,whereas no significant abnormalities were observed in the blank group,low-dose/medium-dose/high-dose Huoluogukang groups,or the positive drug group.Histopathological analysis demonstrated that:compared to the model group,the Huoluogukangtreated groups（low dose,medium dose,high dose）and the positive drug group showed reduced necrotic foci,a lower empty lacunae rate,and increased trabecular bone area,with statistically significant differences（P<0.05）.Serum total cholesterol（CHO）and low-density lipoprotein cholesterol levels decreased,while high-density lipoprotein cholesterol increased significantly in the medium-dose and high-dose Huoluogukang groups compared to the model group（P<0.05）.Serum pro-inflammatory cytokines（TNF-α,IL-1β,IL-6）were markedly reduced,and anti-inflammatory cytokines（IL-10,IL-4）were elevated in the Huoluogukang-treated groups（P<0.05）.Additionally,mRNA expression levels of PPARγand iNOS in femoral head tissue were downregulated（P<0.05）,and protein expression levels of PPARγ,C/EBPα,and iNOS were significantly reduced（P<0.001）.Conclusion:Huoluogukang pills can prevent and treat SONFH by inhibiting the PPARγpathway,correcting lipid metabolism imbalance,maintaining bone homeostasis,and inhibiting chronic inflammation mediated by immune factors in SONFH.更多还原