三七总皂甙对创伤性下肢骨折大鼠碱性成纤维细胞因子和血管内皮生长因子表达的影响

Effect of Panax notoginseng saponins on the expression of basic fibroblast growth factor and vascular endothelial growth factor in rats with traumatic fracture of the lower extremities

目的探讨三七总皂甙(PNS)对创伤性下肢骨折大鼠碱性成纤维细胞因子(b-FGF)和血管内皮生长因子(VEGF)表达的影响。方法 45只SD大鼠构建创伤性下肢骨折大鼠模型,并随机分为低、高剂量实验组和模型组,模型构建成功后,低、高剂量实验组分别予以腹腔注射PNS 100 mg·kg^(-1),200 mg·kg^(-1),模型组予以腹腔注射等体积生理盐水,每日1次,连续干预30 d。分别于药物干预2 h,3 d,10 d后,检测大鼠血浆中D-二聚体(D-D)和血管性血友病因子(v WF)水平;分别于药物干预10 d,20 d,30 d后,用免疫组化法检测大鼠骨组织中b-FGF和VEGF蛋白表达。结果 PNS干预2 h后,模型组和低、高剂量实验组血浆中D-D分别为(0. 64±0. 06),(0. 42±0. 08),(0. 31±0. 05)pg·m L^(-1),v WF分别为(115. 89±12. 06)%,(89. 47±8. 49)%,(72. 89±9. 52)%; PNS干预3 d后,模型组和低、高剂量实验组血浆中D-D分别为(0. 68±0. 05),(0. 55±0. 08),(0. 44±0. 07) pg·m L^(-1),v WF分别为(106. 25±11. 21)%,(85. 12±6. 49)%,(68. 15±8. 21)%; PNS干预10 d后,模型组和低、高剂量实验组血浆中D-D分别为(0. 35±0. 04),(0. 24±0. 07),(0. 21±0. 06)pg·m L^(-1),v WF分别为(76. 59±6. 45)%,(70. 11±5. 41)%,(65. 12±6. 05)%,各组间比较,差异均有统计学意义(均P <0. 05)。PNS干预30 d后,模型组和低、高剂量实验组骨组织中b-FGF相对表达量分别为0. 26±0. 02,0. 33±0. 03,0. 35±0. 03,VEGF相对表达量分别为0. 27±0. 01,0. 34±0. 03,0. 37±0. 06,实验组与模型组比较,差异均有统计学意义(均P <0. 05)。结论 PNS可抑制创伤性骨折后血液高凝状态,且具有保护血管内皮的作用,同时其可增加骨组织中b-FGF和VEGF的表达进而促进骨折愈合。

Objective To investigate the effect of Panax notoginseng saponins （PNS） on the expression of basic fibroblast growth factor （b- FGF） and vascular endothelial growth factor （VEGF） in rats with traumatic fracture of the lower extremities. Methods A model of traumatic fracture of the lower extremities was constructed in 45 cases of SD rats and they were randomly divided into experimental - L/- H group and model group. The experimental - L/- H group received intraperito- heal injection of 100, 200 mg · kg^-1 of PNS, respectively, while the model group was given intraperitoneal injection of the equal amount of normal saline respectively. All groups were given treatment once daily for 30 days. The levels of D - dimer （ D - D） and von willebrand factor （vWF） in rats plasma were detected at 2 h, 3 d and 10 d after drug intervention respectively, the expression of b - FGF and VEGF protein in the bone tissue of rats were detected by immunohistochemical method at 10 d, 20 d and 30 d after drug intervention respectively. Results At 2 h after PNS treatment, the plasma levels of D-Din model group and experimental-L/- H group were （0.64±0.06）, （0.42±0.08）, （0.31 ±0.05） pg·mL^- 1, respectively, the plasma levels of vWF were （ 115.89±12. 06） %, （ 89. 47 ±8. 49 ） %, （72. 89 ± 9. 52） %, respectively. At 3 d after PNS treatment, the plasma levels of D - D in model group and experimental - L/- H group were （0.68±0.05）, （0.55 ±0.08）, （0.44 ±0.07） pg· mL^-1, respectively, the plasma levels of vWF were （ 106. 25±11.21 ） %, （85.12±6. 49 ） %, （68.15±8.21 ） %, respectively. At 10 d after PNS treatment, the plasma levels of D - D in model group and experimental - L/- H group were （0.35 ±0.04）, （0.24± 0.07）, （0. 21±0.06） pg· mL^-1 , respectively, the plasma levels of vWF were （76.59±6.45 ）% , （70. 11±5.41 ）% , （65.12 ±6. 05 ）%, respectively. The differences were statistically significant among all groups （P 〈 0. 05 ）. At 30 d after PNS treatment, the relative expression of b - FGF in the bone tissue of model group and experimental - L/- H group were 0. 26 ：i：0.02, 0. 33 -＋0. 03, 0. 35 ＋0. 03, respectively;the relative expression of VEGF were 0. 27 ±0. 01,0. 34±0. 03, 0. 37±0. 06, respectively. The difference between the experimental - L/- H group and the model group was statistically significant （ P 〈 0. 05 ）. Conclusion PNS exerted protective effect on vascular endothelium by inhibiting blood hypercoagulability after traumatic fracture ; meanwhile, it could increase the expression of b - FGF and VEGF in bone tissue and promote fracture healing.