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背景:阿胶强骨口服液可有效治疗骨折,但其具体的药理学机制仍有待研究。在骨折愈合中,血管内皮生长因子和成纤维细胞生长因子2是促进血管内生以及骨的合成代谢的重要耦联因子。目的:观察阿胶强骨口服液对SD大鼠胫骨骨折愈合过程中骨痂中血管内皮生长因子和成纤维细胞生长因子2表达的影响,探讨阿胶强骨口服液治疗骨折的疗效机制。设计:完全随机对照实验。单位:华中科技大学同济医学院附属协和医院骨伤科研究室。材料:选用90只雌性3月龄SD大鼠,体质量(368±40)g,阿胶强骨口服液(主要成分为阿胶,新疆华世丹药业股份有限公司生产);阳性对照药接骨七厘片(主要成分为当归、乳香、没药、大黄、血竭、骨碎补、自然铜,珠海金沙(湖南)制药有限公司生产)。方法:实验于2005-07/12在华中科技大学同济医学院中西结合骨代谢实验室(省级实验室)完成,采用三点弯曲方法造成大鼠右胫骨中段闭合性骨折后,采用完全随机法分为3组:阿胶强骨口服液组(n=30):按人鼠表面积比率换算等效计量法计算后,每只每次给予阿胶强骨口服液2mL灌胃给药,2次/d;接骨七厘片组(n=30):用蒸馏水配制成225g/L灌胃,2次/d;生理盐水组(n=30):给予同等容量,同等频率的生理盐水灌胃。分别在实验第4,7,14,21,28天采用免疫组织化学方法检测大鼠右胫骨骨痂区血管内皮生长因子和成纤维细胞生长因子2表达的变化,计算平均吸光度值及阳性细胞数(5个视野细胞)。主要观察指标:各组大鼠右胫骨骨痂区血管内皮生长因子和成纤维细胞生长因子2表达(平均吸光度值及阳性细胞数)。结果:纳入大鼠90只均进入结果分析。①血管内皮生长因子表达检测结果:实验开始后4,7,14d,阿胶强骨口服液组大鼠及接骨七厘片组平均吸光度值均高于生理盐水组(P<0.05～0.01),阳性细胞数变化幅度与平均吸光度值一致。②成纤维细胞生长因子2表达检测结果:实验开始后4,7d,阿胶强骨口服液组及骨七厘片组成纤维细胞生长因子2平均吸光度值,均高于生理盐水组(P<0.05～0.01),阳性细胞数变化幅度与平均吸光度值一致。结论:阿胶强骨口服液在骨愈合早中期可通过调节血管内皮生长因子和成纤维细胞生长因子2的表达,促进前成骨细胞和成软骨细胞的有丝分裂、血管内生以及骨的合成代谢达到促骨折愈合的作用。
BACKGROUND: Ejiao Qiangkuang Oral Liquid can effectively treat fractures, but its specific pharmacological mechanism remains to be studied. In fracture healing, vascular endothelial growth factor and fibroblast growth factor 2 are important coupling factors that promote angiogenesis and bone anabolism. OBJECTIVE: To observe the effect of Ejiao Qiangu oral liquid on the expression of vascular endothelial growth factor and fibroblast growth factor 2 in bone callus of SD rats during the process of tibial fracture healing, and to explore the curative effect mechanism of Ejiao Qianggu oral liquid on bone fractures. Design: Completely randomized controlled trials. Unit: Department of Orthopaedics and Trauma, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: A total of 90 female 3-month-old Sprague-Dawley rats were used, and the body weight was (368±40) g. Ejiao Qianggu Oral Liquid (the main ingredient was Ejiao, produced by Xinjiang Hussein Pharmaceutical Co., Ltd.); (The main ingredients are Angelica, Frankincense, Myrrh, Rhubarb, Blood Exhaustion, Drynaria, Natural Copper, produced by Zhuhai Jinsha (Hunan) Pharmaceutical Co., Ltd.). METHODS: The experiment was performed at the Central and Western Bone Metabolism Laboratory (the provincial laboratory) of Tongji Medical College, Huazhong University of Science and Technology from July 2005 to December 12, 2005. After the three-point bending method was used to create a closed fracture in the middle right segment of the right tibia, the method was completely randomized. Divided into 3 groups: Ejiao Qianggu Oral Liquid Group (n=30): Calculated according to the equivalent conversion method of human and mouse surface area ratio, 2 mL of Ejiao Qianggu Oral Liquid was administered to each patient twice a day. The Qiguqiqi tablet group (n=30): Digested water was used to formulate 225 g/L gavage, 2 times/d; normal saline group (n=30): The same volume of saline was given to the same volume. The changes of vascular endothelial growth factor and fibroblast growth factor 2 expression in the right tibia and fibula were detected by immunohistochemistry on days 4, 7, 14, 21, and 28 of the experiment, and the average absorbance and number of positive cells were calculated. (5 visual field cells). MAIN OUTCOME MEASURES: The expression of vascular endothelial growth factor and fibroblast growth factor 2 (average absorbance value and number of positive cells) in the right tibia and fibula in each group. RESULTS: Ninety rats were included in the results analysis. 1Results of vascular endothelial growth factor expression: On the 4th, 7th and 14th days after the start of the experiment, the average absorbance values of the rats in the Ejiao Qianggu Oral Liquid group and the Jieguqi Tablet group were higher than those in the saline group (P<0.05-0.01). The change in cell number is consistent with the average absorbance value. 2 Results of fibroblast growth factor 2 expression: At the 4th and 7th days after the start of the experiment, the average absorbance of fibroblast growth factor 2 in the Ejiao Kegu Oral Liquid group and Guqiqili tablet was higher than that in the saline group (P<0.05~ 0.01), the change in the number of positive cells is consistent with the average absorbance value. Conclusion: Ejiao Qianggu Oral Liquid can regulate the expression of vascular endothelial growth factor and fibroblast growth factor 2 in the early and middle stage of bone healing, promote the mitosis, angiogenesis, and bone anabolism of preosteoblasts and chondroblasts. Promote fracture healing.