吴继云;陈伟南;蒋春华;
WU Jiyun;CHEN Weinan;JIANG Chunhua;904 Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army (Taihu Hospital);Guangxi medical university;

• 1:中国人民解放军联勤保障部队第904医院&无锡市太湖医院
• 2:广西医科大学

摘要(Abstract)：

目的:探讨仙灵骨葆胶囊对老龄去势大鼠骨质疏松性骨折愈合过程血小板衍生生长因子(PDGF)、转化生长因子β(TGF-β)和血管内皮生长因子(VEGF)表达的影响。方法:雌性SD大鼠随机分为假手术组、去势组、仙灵骨葆胶囊高剂量组(高剂量组)和低剂量组,每组16只,去势组、高剂量组和低剂量组大鼠行双侧卵巢切除术,制备骨质疏松模型,假手术组仅做手术,不切除卵巢;术后8周,所有大鼠建立右侧股骨骨折模型;骨折后第2天高剂量组和低剂量组分别给予0.6及0.3 g/kg仙灵骨葆胶囊,假手术组和去势组给予生理盐水灌胃,连续10周;记录4组大鼠骨折前、骨折后2周～8周的体质量,观察各组大鼠骨折后第2、4、8和10周时骨细胞指数、破骨细胞指数、骨折周围软组织的PDGF、TGF-β和VEGF表达水平。结果:骨折10周时,与假手术组比较,其余3组大鼠体质量明显降低(P<0.05);骨折后2周时,去势组、高剂量组和低剂量组大鼠的骨细胞指数、破骨细胞指数、骨折软组织的PDGF、TGF-β和VEGF均有不同程度地增高,至4周时达峰值,第8、10周时降低;与假手术组比较,其余3组大鼠骨细胞指数、破骨细胞指数均明显降低(P<0.05),骨折软组织的PDGF、TGF-β和VEGF明显增高(P<0.05);与去势组比较,高剂量组和低剂量组的骨细胞指数、破骨细胞指数、骨折软组织的PDGF、TGF-β和VEGF均有不同程度地增高(P<0.05)。结论:仙灵骨葆胶囊可促进老龄去势大鼠骨质疏松性骨折愈合过程,其机制可能与仙灵骨葆胶囊提高骨折周围软组织PDGF、TGF-β和VEGF的水平有关。
Objective: To investigate the effect of Xianlinggubao capsules on osteoporotic fracture(OPF) healing after castration in aged rats, and observe its influence on the expression of platelet derived growth factor(PDGF), transforming growth factor beta(TGF-β) and vascular endothelial growth factor(VEGF). Methods: Female SD rats were randomly divided into 4 groups: the sham operation group, the ovariectomized group, the high-dose group(0.6 g/kg Xianlinggubao) and the low-dose group(0.3 g/kg Xianlinggubao), with 16 rats in each group. The ovariectomized group, the high-dose group and the low-dose group were prepared as the OP fracture models. All the 4 groups were administered continuously with pure water, 0.3 g/kg Xianlinggubao capsule and 0.6 g/kg Xianlinggubao capsule for 10 weeks,. The body weights of the 4 groups before fracture and 2 weeks to 10 weeks after fracture were recorded. The bone marrow, bone cell index, osteoclast index, and PDGF, TGF-β, and VEGF expression in soft tissues around the fracture were recorded or detected in 2, 4, 8 and 10 weeks after the establishment of the fracture model. Results: There was no statistical difference in body mass of the sham operation group before and 2～10 weeks after the fracture(P>0.05). Compared with the sham operation group, the body weight of the other 3 groups was significantly lower, and the difference was statistically significantly(P<0.05). After fracture, the model group had more fibrous epiphyseal and cartilage defects than the sham operation group, the high-dose and low-dose group. There was no significant difference in bone cell index, osteoclast index, PDGF, TGF-β and VEGF in the soft tissues of the sham operation group 2～10 weeks after the fracture(P>0.05). Compared with the sham operation group, the bone model index and osteoclast index of other 3 groups significantly decreased after 2～10 weeks of fracture(P<0.05). The PDGF, TGF-β and VEGF of the soft tissues of the fracture significantly increased(P<0.05). Compared with the sham operation group, the bone cell index, osteoclast index, PDGF, TGF-β and VEG of the soft tissues of the other 3 groups increased to varying degrees, reaching a peak in 4 weeks, followed by a decrease of 8～10 weeks(P<0.05). 2～10 weeks after the fracture model was established, compared with the low-dose group, the bone cell index, osteoclast index, PDGF, TGF-β and VEG of fracture soft tissues of the high-dose group increased, but the difference was not statistically significant(P>0.05). Conclusion: Xianlinggubao capsules could promote the healing process of OPF after castration in aged rats, which may be related to the improvement of the relative expression of PDGF, TGF-β and VEGF in the soft tissues around the fracture.

关键词(KeyWords)： 仙灵骨葆胶囊;去势;骨质疏松性骨折;血小板衍生生长因子;转化生长因子β;血管内皮生长因子;大鼠,Sprague-Dawley
Xianlinggubao capsules;castration;osteoporotic fracture;platelet derived growth factor;transforming growth factor beta;vascular endothelial growth factor;rats,Sprague-Dawley

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81560408)

作者(Author): 吴继云;陈伟南;蒋春华;
WU Jiyun;CHEN Weinan;JIANG Chunhua;904 Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army (Taihu Hospital);Guangxi medical university;

Email:

DOI: 10.19367/j.cnki.1000-2707.2019.05.009

参考文献(References)：

• [1] SCHOUSBOE J T,TIEN V,TAYLOR B C,et al.Prediction of incident major osteoporotic and hip fractures by trabecular bone score (TBS) and prevalent radiographic vertebral fracture in older men[J].J Bone Miner Res,2016,31(3):690-697.
• [2] YOO J H,MOON S H,HA Y C,et al.Osteoporotic fracture:2015 position statement of the Korean society for bone and mineral research[J].J Bone Metab,2015,22(4):175-181.
• [3] KIM H Y,HA Y C,KIM T Y,et al.Healthcare costs of osteoporotic fracture in Korea:information from the national health insurance claims database,2008-2011[J].J Bone Metab,2017 ,24(2):125-133.
• [4] 陈鑫,朱雄白,林文军,等.仙灵骨葆胶囊治疗绝经后骨质疏松的疗效及其机制研究[J].中国临床药理学杂志,2015,31(10):827-829.
• [5] 钱雪丰,曹平,刘拴,等.仙灵骨葆辅助外科治疗老年妇女 Colles 骨折的愈合时间、钙磷含量及骨代谢的评估[J].海南医学院学报,2017,23(2):281-284.
• [6] YOKOTA J,CHOSA N,SAWADA S,et al.PDGF-induced PI3K-mediated signaling enhances the TGF-β-induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner[J].Int J Mol Med,2014,33(3):534-542.
• [7] POUNTOS I,GEORGOULI T,HENSHAW K,et al.Release of growth factors and the effect of age,sex,and severity of injury after long bone fracture:A preliminary report[J].Acta Orthop,2013,84(1):65-70.
• [8] HU K,OLSEN B R.The roles of vascular endothelial growth factor in bone repair and regeneration[J].Published in Final Edited Form as:Bone,2016,91(10):30-38.
• [9] 王昌兴,刘琦,董黎强,等.浓缩自体骨髓移植结合金葡液局部注射对骨质疏松性骨折愈合过程中 BMP-2和VEGF表达的调控[J].浙江中医药大学学报,2014,(2):188-195.
• [10]高伟,陈游,谭丽,等.合并脑外伤肢体骨折患者血清中血管内皮生长因子、血小板衍生生长因子的含量分析 [J].实用骨科杂志,2013,19(2):136-138;192.
• [11]王占义,胡东旭,杨晓琳,等.IGF-1 与 VEGF 促兔下颌骨骨折愈合作用的相关性研究 [J].中国实验诊断学,2013,17(12):2147-2149.
• [12]赵萍.消肿止痛合剂对大鼠骨折愈合中VEGF 表达的影响[J].西部中医药,2013,(11):16-18.
• [13]李鹏,冉祥根,尉继伟,等.丹参注射液对模型兔骨折围手术期细胞因子TGF-β、TNF影响的实验研究[J].中国中医急症,2018,27(10):1765-1767;1770.
• [14]胡岚翔,余化龙,刘亚东,等.中药熏洗联合CPM机功能锻炼改善胫骨骨折手术患者关节功能和疼痛的效果及对血清BMP-7、TGF-β1及bFGF水平的影响[J].四川中医,2018,36(9):142-144.
• [15]覃裕,邱冰,朱思刚,等.仙灵骨葆胶囊治疗骨质疏松症的疗效及其对骨代谢及骨转换指标的影响分析[J].中国骨质疏松杂志,2015,21(9):1056-1060.
• [16]朱晓波.仙灵骨葆胶囊联合透明质酸对膝骨性关节炎患者血清炎症因子水平的影响及疗效观察[J].新中医,2016,48(3):104-106.
• [17]李菲,张洋洋,蔡锐,等.淫羊藿苷通过上调VEGF信号通路促进脑低灌注大鼠的血管发生[J].遵义医学院学报,2018,41(5):533-538.
• [18]李功营,宋金带,王剑.淫羊藿总黄酮和薯蓣皂苷元联合用药对自然围绝经期大鼠影响的实验研究[J].新中医,2017,49(1):9-11.
• [19]成魁,陈克明,葛宝丰,等.淫羊藿苷与金雀异黄酮通过血管再生和抗炎症反应途径抑制卵巢切除大鼠骨丢失的比较研究[J].中药材,2014,37(4):627-631.
• [20]宁涛,胡勇.复方续断三七提取物对家兔骨折愈合的促进作用及其机制[J].西安交通大学学报(医学版),2016,37(6):886-891.
• [21]张波,徐博,吴昊,等.续断对兔骨折愈合过程中相关基因表达和血钙、磷含量的影响[J].氨基酸和生物资源,2016,38(2):54-57.
• [22]魏合伟,林一峰,曲崇正,等.中药骨康含药血清对骨质疏松性骨折愈合过程中血小板衍生生长因子表达的影响[J].中国组织工程研究与临床康复,2008,12(37):7290-7293.

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