补骨脂提取物对骨质疏松模型大鼠趋化因子配体炎4、症反应及骨代谢的影响及机制研究  

Effects and mechanisms of Psoralea corylifolia extract on chemokine ligand 4,inflammatory response,and bone metabolism in osteoporosis model rats

作　　者：贾川 张兴州[1] 王雨辰[1] 钱志鹏 何樟宁 朱文科 JIA Chuan;ZHANG Xingzhou;WANG Yuchen;QIAN Zhipeng;HE Zhangning;ZHU Wenke(Department of Orthopedics,Wujin Traditional Chinese Medicine Hospital,Changzhou 213161,China)

机构地区：[1]常州市武进中医医院骨伤科,常州213161

出　　处：《北京中医药》2024年第10期1138-1142,共5页Beijing Journal of Traditional Chinese Medicine

基　　金：江苏省中医药科技发展计划项目(QN202221);常州市科技局面上项目(CJ20230008);常州市卫生健康委青苗人才项目(CZQM2020122)。

摘　　要：目的 探讨补骨脂提取物对骨质疏松模型大鼠趋化因子配体4 (CCL4)、炎症反应及骨代谢的影响及机制。方法 选择无特定病原体(SPF)级SD雌性大鼠55只,选取10只大鼠作为空白组,其余45只建立骨质疏松模型,将40只造模成功大鼠分为模型组及补骨脂提取物低、中、高剂量组,各10只。造模第9周,补骨脂提取物低、中、高剂量组分别给予补骨脂提取物药液50、100、200 mg/(kg·d)灌胃,空白组、模型组给予生理盐水10 mL/(kg·d)灌胃。均连续干预8周。干预8周后,处死大鼠,获取股骨组织,HE染色光镜下观察股骨病理形态改变;酶联免疫吸附法检测股骨组织中CCL4、炎症因子[肿瘤坏死因子-ɑ(TNF-ɑ)、白细胞介素6 (IL-6)];用电化学发光法检测骨代谢指标[骨钙素(OC)、Ⅰ型原胶原N-端前肽(P1NP)];用Western blotting法检测股骨组织中转化生长因子β1 (TGF-β1)/Smad4信号通路相关蛋白表达。结果 空白组股骨骨髓腔面积最小,模型组骨髓腔面积最大,补骨脂提取物低、中、高剂量组骨髓腔面积依次缩小,但仍大于空白组。与模型组比较,补骨脂提取物低、中、高剂量组CCL4水平低(P<0.05),且呈剂量依赖性(P<0.05)。与空白组比较,模型组OC、PINP水平低(P<0.05);与模型组比较,补骨脂提取物低、中、高剂量组OC、PINP水平高(P<0.05),且呈剂量依赖性(P<0.05)。与空白组比较,模型组TNF-ɑ、IL-6水平高(P<0.05);与模型组比较,补骨脂提取物低、中、高剂量组TNF-ɑ、IL-6水平低(P<0.05),且呈剂量依赖性(P<0.05)。与空白组比较,模型组TGF-β1、Smad4蛋白相对表达量低(P<0.05);与模型组比较,补骨脂提取物低、中、高剂量组TGF-β1、Smad4蛋白相对表达量高(P<0.05),且呈剂量依赖性(P<0.05)。结论 补骨脂提取物可使骨质疏松大鼠CCL4水平下降,抑制炎症反应,改善骨代谢,其机制可能与TGF-β1/Smad4信号通路被抑制有关。Objective To investigate the effects and mechanisms of Psoralea corylifolia extract on chemokine ligand 4(CCL4),inflammatory response,and bone metabolism in osteoporosis model rats.Methods A total of 55 SPF-grade female SD rats were selected,with 10 rats assigned to the blank group.The remaining 45 rats were used to establish an osteoporosis model.Forty successfully modeled rats were divided into the model group and low,medium,and high dose groups of P.corylifolia extract,with 10 rats in each group.On the 9th week of modeling,the low,medium,and high dose groups were administered P.corylifolia extract at doses of 50,100,and 200 mg/(kg•d)by gavage,respectively.The blank and model groups were given physiological saline at 10 mL/(kg·d).The intervention lasted for 8 weeks.After 8 weeks of intervention,the rats were euthanized,and femur tissue was collected.Histopathological changes in the femur were observed under a light microscope after hematoxylin-eosin(HE)staining.CCL4 and inflammatory cytokines[tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)]were detected by enzyme-linked immunosorbent assay(ELISA).Bone metabolism markers[osteocalcin(OC),type I collagen N-terminal propeptide(P1NP)]were detected by electrochemiluminescence.Western blotting was used to detect the expression of transforming growth factor-beta 1(TGF-β1)/Smad4 signaling pathway-related proteins in the femur tissue.Results The bone marrow cavity area was smallest in the blank group and largest in the model group.The bone marrow cavity area in the low,medium,and high-dose P.corylifolia extract groups gradually decreased,but remained larger than that in the blank group.Compared to the model group,the CCL4 level in the low,medium,and high-dose groups was significantly lower(P<0.05),and the level of CCL4 decreased in a dose-dependent manner(P<0.05).The levels of OC and P1NP were lower in the model than in the blank group(P<0.05).The OC and P1NP levels in the low,medium,and high-dose P.corylifolia extract groups were higher than that in the mode

关 键 词：骨质疏松 补骨脂提取物 趋化因子配体4 炎症反应 骨代谢 转化生长因子β1/Smad4信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]