生骨再造丸对兔激素性股骨头坏死VEGF及FLT-1表达的影响

doi:10.12092/j.issn.1009-2501.2018.08.006

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (8): 874-880.doi: 10.12092/j.issn.1009-2501.2018.08.006

生骨再造丸对兔激素性股骨头坏死VEGF及FLT-1表达的影响

曹林忠^1,2,3，汪小敏¹，张虎林²，郭成龙²，苏亮磊¹，刘新宇⁴

¹甘肃中医药大学中医临床学院，兰州 730000，甘肃； ²甘肃中医院大学附属医院脊柱外科，兰州 730020，甘肃；³甘肃省中医药防治慢性疾病重点实验室，兰州 730020，甘肃；⁴甘肃省第二人民医院中医科，兰州 730000，甘肃

收稿日期:2018-01-16 修回日期:2018-03-28 出版日期:2018-08-26 发布日期:2018-08-28
通讯作者: 刘新宇，男，住院医师，研究方向：中医药防治骨伤疾病。 Tel：13893453204 E-mail:865804815@qq.com
作者简介:曹林忠，男，主任医师，副教授，硕士生导师，研究方向：中医药防治骨伤疾病。 Tel:13893453204 E-mail:clzh1@163.com
基金资助:
甘肃省自然科学基金项目（1308RJZA293）；2014年甘肃省卫生行业科研管理项目（GWGL2014-65）；2014年甘肃中医药大学中青年基金项目（ZQ2014-13）

Effects of Shenggu zaizao pills on VEGF and FLT-1 expression in steroid-induced avascular necrosis of femoral head in rabbits

CAO Linzhong ^1,2,3, WANG Xiaomin ¹, ZHANG Hulin ², GUO Chenglong², SU Lianglei ¹, LIU Xinyu ⁴

¹ College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000，Gansu，China; ² Spinal Surgery, Affiliated Hospital of Gansu Hospital of Traditional Chinese Medicine, Lanzhou 730020 ，Gansu，China； ³Key Laboratory of Prevention and Treatment of Chronic Diseases of Traditional Chinese Medicine in Gansu Province ，Lanzhou 730020，Gansu，China; ⁴ Gansu Province Second People's Hospital of Traditional Chinese Medicine，Lanzhou 730000，Gansu，China

Received:2018-01-16 Revised:2018-03-28 Online:2018-08-26 Published:2018-08-28

摘要/Abstract

摘要：

目的: 观察生骨再造丸对激素性股骨头坏死兔的血管内皮生长因子（VEGF）及受体fms样酪氨酸激酶（VEGFR-1/FLT-1）表达的影响，探讨其对激素性股骨头坏死（SANFH）的干预机制。方法: 从80只日本大耳白兔中随机抽取10只作为空白组（A组），其余70只采用小剂量内毒素（LPS）联合大剂量激素的方法建立SANFH模型，造模过程死亡共计4只，造模后两周，随机抽取6只，应用空气注射栓塞法处死并取出股骨头标本制作病理切片，经HE染色处理在高倍（×400）光学显微镜下观察其病理变化，证实早期SANFH造模成功后，将剩余的早期SANFH模型日本大耳白兔再次随机分为4组：模型组（B组）、生骨再造丸低剂量组（C组）、生骨再造丸中剂量组（D组）以及生骨再造丸高剂量组（E组），每组15只，依照实验设计进行药物灌胃处理，分别在用药第2、4、8周末取出股骨头标本，经HE染色观察股骨头的病理变化，并且采用免疫组化检测VEGF及其受体FLT-1蛋白表达。结果: HE病理切片显示：同一取材时间条件下，B组骨细胞空骨陷窝数量较多，C、D、E组较B组空骨陷窝明显减少；随着时间推移，C、D及E组骨细胞空骨陷窝数量较前期各组有不同程度减少，E组减少最为显著。免疫组化检测：C、D及E组阳性颗粒较B组多，E组阳性颗粒增加最为显著(P＜0.05)；随着时间推移，C、D及E各组阳性颗粒较前期各组也存在不同程度增加，E组增加最显著(P＜0.05)。结论: 生骨再造丸通过上调VEGF及受体FLT-1蛋白的表达促进血管再生，改善骨微循环，进而促进坏死骨组织的修复。

关键词: 生骨再造丸, 激素性股骨头坏死, 血管内皮生长因子, fms样酪氨酸激酶

Abstract:

AIM: To explore the intervention mechanism of Shenggu zaizao pills on the steroid induced avascular necrosis of femoral head (SANFH) of rabbit by investigating its effect on vascular endothelial growth factor (VEGF) and its receptor FLT-1. METHODS: Ten Japanese rabbits were randomly selected as blank normal group (group A).The remaining 70 Japanese rabbits were chosen to establish SANFH model, and were administered with low doses of Escherichia coli endotoxin (LPS) combined with high dose of Hormone, four died during the modeling process. Two weeks after establishing model, six Japanese rabbits were randomly selected and sacrificed by air vein injection. HE staining was applied to the pathological sections, and the pathological change of femoral head tissue was observed under high power (×400) optical microscope. When it is confirmed that SANFH model was established successfully, the remaining Japanese rabbits were randomly divided into 4 groups: model group (group B), and low-, medium- and high- dose of Shenggu zaizao pills (group C, D, E), twelveJapanese rabbits in each group. RESULTS:HE pathological sections showed that the number of empty lacuna in B group was the highest at the same time point, and it was more significantly reduced in group C, D and E as compared with group B (P＜0.05)；With time passing，group C, D and E were more significantly reduced as compared with early weeks (P＜0.05). CONCLUSION: Shenggu zaizao pills can promote angiogenesis by up-regulating the expression of VEGF and its receptor FLT-1, which assists the repair of necrotic bone tissue.

Key words: Shenggu zaizao pills, teroid induced avascular necrosis of femoral head (SANFH), VEGF, FLT-1

中图分类号:

R965.2

曹林忠，汪小敏，张虎林，郭成龙，苏亮磊，刘新宇. 生骨再造丸对兔激素性股骨头坏死VEGF及FLT-1表达的影响[J]. 中国临床药理学与治疗学, 2018, 23(8): 874-880.

CAO Linzhong, WANG Xiaomin, ZHANG Hulin, GUO Chenglong, SU Lianglei, LIU Xinyu. Effects of Shenggu zaizao pills on VEGF and FLT-1 expression in steroid-induced avascular necrosis of femoral head in rabbits[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(8): 874-880.

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生骨再造丸对兔激素性股骨头坏死VEGF及FLT-1表达的影响

Effects of Shenggu zaizao pills on VEGF and FLT-1 expression in steroid-induced avascular necrosis of femoral head in rabbits

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