[关键词]
[摘要]
目的 观察骨蚀再造丸对激素性股骨头坏死(SONFH)大鼠骨代谢及脂质代谢的影响。方法 将 60 只 SD 大鼠随机分为空白组、模型组、仙灵骨葆胶囊组(0.97 g·kg-1 )及骨蚀再造丸低、中、高剂量组(1.62、3.24、6.48 g·kg-1 ), 每组 10 只。采用腹腔注射脂多糖(10 μg·kg-1 ,连续 2 d,1 次/d)+左侧臀肌注射甲波尼龙琥珀酸钠注射液 (100 mg·kg-1 ,3 次/周,连续 4 周)复制 SONFH 大鼠模型。灌胃给药,灌胃体积 10 mL·kg-1 ,每天 1 次,连续 灌胃 4 周。采用 ELISA 法检测大鼠血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋 白(LDL)、脂联素(APN)、碱性磷酸酶(ALP)和骨钙素(BGP)水平;HE 染色法观察股骨头组织病理变化;免疫 组化法测定股骨头组织中 OPG、Runx2 蛋白表达水平;通过生物力学测定骨骼强度。结果 与空白组比较,模 型组大鼠体质量明显降低(P<0.05);血清 TC、TG、LDL 水平显著升高(P<0.05,P<0.01),HDL、APN、 BGP、ALP 水平显著降低(P<0.01);空骨陷窝率显著升高(P<0.01),骨小梁面积比显著降低(P<0.01);股骨 头组织中的 OPG、Runx2 蛋白表达水平显著降低(P<0.01);股骨头骨骼强度显著降低(P<0.01)。与模型组比 较,各给药组大鼠体质量明显升高(P<0.05);血清 TC、TG、LDL 水平显著降低(P<0.05,P<0.01),HDL、 APN、BGP、ALP 水平显著升高(P<0.05,P<0.01);空骨陷窝率显著降低(P<0.01),骨小梁面积比显著升高 (P<0.05,P<0.01);股骨头组织中 OPG 蛋白表达水平显著升高(P<0.01);股骨头骨骼强度显著升高(P<0.01)。 与模型组比较,仙灵骨葆胶囊组及骨蚀再造丸中、高剂量组大鼠股骨头组织中 Runx2 蛋白表达水平显著升高 (P<0.01)。结论 骨蚀再造丸能够增加 SONFH 大鼠股骨头内的骨小梁面积,降低空骨陷窝率,增强骨骼强 度,可能与其调节骨代谢及脂质代谢平衡,增强骨形成,调节骨稳态,发挥滋补肝肾、强筋健骨的作用 有关。
[Key word]
[Abstract]
Objective To investigate the effects of Gushi Zaizao Pills on bone metabolism and lipid metabolism in rats with steroid-induced osteonecrosis of the femoral head (SONFH). Methods Sixty SD rats were randomly divided into a blank group, model group, Xianling Gubao Capsules group (0.97 g·kg-¹), and low-, medium-, and high-dose Gushi Zaizao Pills groups (1.62,3.24,6.48 g·kg- ¹),with 10 rats per group. The SONFH model was established via intraperitoneal injection of lipopolysaccharide (10 μg·kg-1 , once daily for 2 consecutive days) combined with left gluteal muscle injection of Methylprednisolone Sodium Succinate (100 mg·kg-1 , three times weekly for 4 weeks). Intragastric administration (10 mL·kg-1 ,once daily) was performed for 4 weeks. Serum levels of total cholesterol (TC), triglycerides (TG),high-density lipoprotein (HDL),low-density lipoprotein (LDL),adiponectin (APN),alkaline phosphatase (ALP),and osteocalcin (BGP) were measured by ELISA. Pathological changes in femoral head tissues were observed using HE staining. Immunohistochemistry was used to determine protein expression levels of osteoprotegerin (OPG) and Runx2 in femoral head tissues. Bone mechanical strength was evaluated using biomechanical testing. Results Compared with the blank group,the model group showed a significant decrease in body mass (P< 0.05); serum TC, TG, and LDL levels were significantly increased (P<0.05, P<0.01), while HDL, APN, BGP,and ALP levels were significantly decreased (P<0.01); the empty bone lacunae rate was significantly elevated (P<0.01),and the trabecular bone area ratio was markedly reduced (P<0.01); protein expression levels of OPG and Runx2 in femoral head tissues were significantly downregulated (P<0.01); and femoral bone mechanical strength was significantly reduced (P<0.01). Compared with the model group, all treatment groups exhibited a significant increase in body mass (P<0.05); serum TC, TG, and LDL levels were significantly decreased (P<0.05, P< 0.01),while HDL,APN,BGP,and ALP levels were significantly increased (P<0.05,P<0.01); the empty bone lacunae rate was significantly reduced (P<0.01),and the trabecular bone area ratio was significantly elevated (P< 0.05, P<0.01); OPG protein expression in femoral head tissues was significantly upregulated (P<0.01); and femoral bone mechanical strength was significantly enhanced (P<0.01). Compared with the model group,the Xianling Gubao Capsules group and the medium- and high-dose Gushi Zaizao Pills groups showed significantly increased Runx2 protein expression in femoral head tissues (P<0.01). Conclusion Gushi Zaizao Pills increase trabecular bone area, reduce empty bone lacunae rate,and enhance bone mechanical strength in SONFH rats,potentially by regulating bone and lipid metabolism,promoting bone formation,restoring bone homeostasis,and exerting effects of tonifying the liver and kidney while strengthening tendons and bones.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金地区科学基金项目(81860401);河南省自然科学基金项目(232300421193);河南省医学科技攻关计划项目 (SBGJ202103103);河南省中医药科学研究专项课题(2022ZY1182);河南省重点研发与推广专项(科技攻关) 项目(232102311202)。