| 武通,陈东宁,许占江.基于VEGF/VEGFR-2信号通路研究淫羊藿苷促进大鼠胫骨干骨折愈合的作用机制[J].浙江中医药大学学报,2021,45(3):282-288, 293. |
| 基于VEGF/VEGFR-2信号通路研究淫羊藿苷促进大鼠胫骨干骨折愈合的作用机制 |
| Mechanism of Icariin in Healing of Tibial Shaft Fracture in Rats Based on VEGF/VEGFR-2 Signaling Pathway |
| DOI：10.16466/j.issn1005-5509.2021.03.016 |
| 中文关键词: 胫骨干骨折 愈合 血管新生 淫羊藿苷 血管内皮生长因子 血管内皮生长因子受体-2 |
| 英文关键词: tibial shaft fracture healing angiogenesis icariin vascular endothelial growth factor vascular endothelial growth factor receptor-2 |
| 基金项目:河南省医学科技攻关计划(182102310531) |
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| 中文摘要: |
| [目的]基于血管内皮生长因子/血管内皮生长因子受体-2(vascular endothelial growth factor/vascular endothelial growth factor receptor-2，VEGF/VEGFR-2)信号通路研究淫羊藿苷(icariin，ICA)对大鼠胫骨干骨折愈合的影响。[方法]将41只胫骨干骨折模型SD大鼠随机分为对照组，ICA低、高剂量组，每组各10只，另设阳性药物组，大鼠11只。ICA低、高剂量组以40、80mg/(kg·d)的ICA腹腔注射，阳性药物组以0.4mL复方骨肽注射液腹腔注射。对照组以等量0.9%氯化钠溶液腹腔注射，各组均为1次/d，连续21d。干预第7、14、21天进行微计算机断层扫描技术(micro-computed tomography，Mirco-CT)活体扫描，计算样本骨体积分数(bone volume/total volume，BV/TV)，骨小梁数量(trabecular number，Tb.N)。脱颈处死大鼠，进行下肢生物力学测试，采用苏木精-伊红(hematoxylin-eosin，HE)染色观察骨痂组织血管新生情况，实时荧光定量聚合酶链式反应(quantitative Real-time polymerase chain reaction，QRT-PCR)检测骨痂组织VEGF、VEGFR-2 mRNA相对表达量，Western blot检测骨痂组织VEGF、VEGFR-2蛋白相对表达量。[结果]与对照组比较，ICA低、高剂量组、阳性药物组BV/TV更高，Tb.N更多，最大载荷更大，新生血管数量增多，面积也更大，VEGF、VEGFR-2 mRNA及蛋白相对表达量较高(P＜0.05)；与ICA低剂量组比较，ICA高剂量组、阳性药物组BV/TV更高，Tb.N更多，最大载荷更大，新生血管数量增多，面积也更大，VEGF、VEGFR-2 mRNA及蛋白相对表达量较高(P＜0.05)；与ICA高剂量组比较，阳性药物组BV/TV更高，Tb.N更多，最大载荷更大，新生血管数量增多，面积也更大，VEGF、VEGFR-2 mRNA及蛋白相对表达量较高(P＜0.05)。[结论]ICA可加快胫骨干骨折大鼠骨量新生，促进血管形成，增强抵抗外力冲击的能力，且该效应呈剂量依赖性，推测可能与上调VEGF、VEGFR-2表达有关。 |
| 英文摘要: |
| [Objective] To study the effect of icariin(ICA) on the healing of tibial shaft fractures in rats based on the vascular endothelial growth factor/vascular endothelial growth factor receptor-2(VEGF/VEGFR-2) signaling pathway. [Methods]Forty-one tibial shaft fracture model SD rats were randomly divided into control group， ICA low-dose and high-dose groups， with 10 in each， and 11 in positive drug group. ICA low and high-dose groups were injected intraperitoneally with 40， 80 mg/(kg·d) ICA， and positive drug group was injected intraperitoneally with 0.4mL of compound Osteopeptide injection. Control group was injected intraperitoneally with the same amount of 0.9% sodium chloride solution， 1 time/d， continuous for 21 days. On the 7th， 14th， and 21st day of the intervention， micro-computed tomography(Mirco-CT) biopsy was performed， the sample bone volume/total volume(BV/TV) and trabecular number(Tb.N) was calculated. After the last Mirco-CT in vivo scan， the rats were sacrificed by cervical dislocation and biomechanical testing of lower limbs was carried out， the angiogenesis of callus tissue was observed by hematoxylin-eosin(HE) staining. The relative expression of VEGF and VEGFR-2 mRNA of callus tissue was detected by quantitative Real-time polymerase chain reaction(QRT-PCR)， and the relative expression of VEGF and VEGFR-2 protein of callus tissue was detected by Western blot. [Results] Compared with control group， ICA low， high-dose group and positive drug group had higher BV/TV， Tb.N， maximum load， number of new blood vessels， larger area of new blood vessels and higher relative expression of VEGF and VEGFR-2 mRNA and protein(P＜0.05). Compared with ICA low-dose group， ICA high-dose group and positive drug group had higher BV/TV， Tb.N， maximum load， number of new blood vessels， larger area of new blood vessels， and higher relative expression of VEGF and VEGFR-2 mRNA and protein(P＜0.05). Compared with ICA high-dose group， positive drug group had higher BV/TV， Tb.N， maximum load， number of new blood vessels， larger area of new blood vessels， and higher relative expression of VEGF and VEGFR-2 mRNA and protein(P＜0.05). [Conclusion] ICA can accelerate the bone regeneration of tibial shaft fracture rats， promote the formation of blood vessels， enhance the ability to resist external force shock， and the effect is dose-dependent. It is speculated that it may be related to the up-regulation of VEGF and VEGFR-2 expression. |
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