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冯海波,王怡璇,姚金龙,熊辉.桃红四物汤对创伤性股骨头坏死大鼠组织形态学及VEGFR2、Dll4表达的影响[J].湖南中医药大学学报英文版,2023,43(7):1188-1193.[Click to copy
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| 桃红四物汤对创伤性股骨头坏死大鼠组织形态学及VEGFR2、Dll4表达的影响 |
| 冯海波,王怡璇,姚金龙,熊辉 |
| (湖南中医药大学第二附属医院, 湖南 长沙 410005;湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 通过观察桃红四物汤对创伤性股骨头坏死大鼠血管内皮细胞生长因子受体2（vascular endothelial growth factor receptor 2，VEGFR2）、Delta样配体4（Delta-like 4，Dll4）蛋白表达的影响，探究其防治创伤性股骨头坏死的作用机制。方法 将44只大鼠采用随机数字表法分为正常组（10只）和造模组（34只）。造模组行创伤性股骨头坏死造模；8周后从正常组和造模组分别随机取2只进行对比检测造模是否成功。将造模成功的剩余32只大鼠按随机数字表法分为模型组及桃红四物汤低、中、高剂量组，每组8只；加上正常组剩余大鼠8只，共计5组。正常组和模型组予以生理盐水灌胃；桃红四物汤低、中、高剂量组分别予以9、18、36 g/kg桃红四物汤灌胃。持续4周后采集股骨头标本，采用micro-CT观察股骨头组织形态学，光镜下检测空骨陷窝率，免疫组织化学法测定VEGFR2和Dll4的蛋白表达水平。结果 与正常组对比，其余4组大鼠股骨头均有不同程度的骨质破坏、软骨面塌陷及空骨陷窝率升高（P<0.05）；模型组和桃红四物汤低剂量组VEGFR2蛋白表达均下降（P<0.05）；桃红四物汤中、高剂量组Dll4蛋白表达明显增加（P<0.05）。与模型组对比，桃红四物汤中、高剂量组大鼠股骨头软骨形态改善，组织空骨陷窝率下降（P<0.05）；桃红四物汤低、中、高剂量组VEGFR2蛋白表达均升高（P<0.05）；桃红四物汤中、高剂量组Dll4蛋白表达升高（P<0.05）。结论 桃红四物汤能有效降低创伤性股骨头坏死骨组织空骨陷窝、改善组织形态，可能与增加VEGFR2、Dll4蛋白的表达、激活VEGF/Notch信号通路有关。 |
| 关键词: 桃红四物汤 组织形态学 创伤性股骨头坏死 血管内皮细胞生长因子受体2 Delta样配体4 血管重建 |
| DOI：10.3969/j.issn.1674-070X.2023.07.006 |
| Received:January 11, 2023 |
| 基金项目:湖南省自然科学基金项目（2019JJ50458）；湖南省教育厅优秀青年项目（20B447）；湖南省中医骨伤临床医学研究中心项目（2020SK4013）；湖南中医药大学校级科研联合项目（2020XJJJ054）。 |
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| Effects of Taohong Siwu Decoction on histomorphology and expressions of VEGFR2 and Dll4 in rats with traumatic osteonecrosis of the femoral head |
| FENG Haibo,WANG Yixuan,YAO Jinlong,XIONG Hui |
| (The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To observe the effects of Taohong Siwu Decoction (THSWD) on the expressions of vascular endothelial growth factor receptor 2 (VEGFR2)and Delta-like 4 (Dll4) proteins in rats with traumatic osteonecrosis of the femoral head (ONFH), so as to explore its mechanism of action in preventing and treating this disease. Methods Totally 44 rats were randomized into normal group (n=10) and modeling group (n=34) using the random number table method. Modeling group underwent traumatic ONFH modeling; after 8 weeks, 2 rats were randomly selected from normal group and 2 rats from modeling group, for comparative testing to determine whether the modeling was successful. The remaining 32 rats with successful modeling were randomly subdivided into model group and low-, medium-, and high-dose THSWD groups using the random number table method, with 8 rats in each group; with the 8 remaining rats from normal group, totally 5 groups were set. Normal group and model group were given normal saline by gavage; low-, medium-, and high-dose THSWD groups were given 9, 18, and 36 g/kg THSWD by gavage, respectively. After 4 weeks of continuous treatment, femoral head specimens were collected, and the morphology of femoral head tissues was observed using micro-CT; the rate of empty bone lacuna was checked by light microscopy; the expression levels of VEGFR2 and Dll4 proteins were measured using immunohistochemistry. Results Compared with normal group, the other four groups of rats showed varying degrees of bone destruction, cartilage surface collapse, and an increase in the rate of empty bone lacuna (P<0.05); the expression of VEGFR2 protein decreased in both model group and low-dose THSWD group (P<0.05); the expression of Dll4 protein was significantly higher in medium- and high-dose THSWD groups (P<0.05). Compared with model group, the morphology of the femoral head cartilage in medium- and high-dose THSWD groups improved, and the rate of empty bone lacunae in the tissue decreased (P<0.05); the expression of VEGFR2 protein increased in low-, medium-, and high-dose THSWD groups (P<0.05); the expression of Dll4 protein increased in medium- and high-dose THSWD groups (P<0.05). Conclusion THSWD can effectively reduce the empty bone lacunae of traumatic ONFH and improve the tissue morphology, which may be related to increasing the expressions of VEGFR2 and Dll4 proteins and activating the VEGF/Notch signaling pathway. |
| Key words: Taohong Siwu Decoction histomorphology traumatic osteonecrosis of the femoral head vascular endothelial growth factor receptor 2 Delta-like 4 vascular reconstruction |
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