目的：比较新型一期给药方案与传统三期给药方案对骨折愈合的促进作用，并初步探究其对骨形态发生蛋白（BMP）/Sma和Mad相关蛋白（Smad）通路的激活效应。方法：选取24只雄性SD大鼠，随机分为空白对照组、模型对照组、一期给药组（全程予综合方）和三期给药组（1~7 d予复元活血汤，8~28 d予和营止痛汤，28 d后予健步虎潜丸）。术后行X射线评估大鼠骨折愈合程度；测定（Ca）、磷（P）、碱性磷酸酶（ALP）、酸性磷酸酶（ACP）水平；苏木精-伊红（HE）染色观察骨痂组织愈合情况；免疫组化检测BMP2、Runt相关转录因子（Runx2）、Smad1蛋白水平；RT-qPCR检测BMP2、Runx2、Smad1的mRNA表达水平。结果：与模型对照组相比，一期给药组和三期给药组的骨折愈合进程均明显加快，一期给药组为著。模型对照组的ALP为（165±4.7）U/L，一期给药组和三期给药组分别为（233±12.2）U/L和（174±20.3）U/L，ALP在一期给药组中显著升高，提示其加速骨折修复显著优于模型对照组和三期给药组。一期给药组的ACP水平为0.192±0.027，显著低于模型对照组的0.340±0.017和三期给药组的0.265±0.014。HE染色显示，一期给药组的局部炎症浸润明显减少，软骨及新骨形成丰富；三期给药组亦见炎症减轻及胶原/软骨组织增多。免疫组化表明，一期给药组的Runx2表达水平为57.1%±5.9%，显著高于模型对照组的41.6%±3.1%和三期给药组的48.3%±4.0%，Smad和BMP2亦有不同程度的升高，RT-qPCR检测结果与上述免疫组化结果一致。结论：一期给药方案通过激活BMP/Smad信号通路有效促进骨折成骨与重塑，其效果优于三期给药方案。

Objective To compare the promotive effects of the novel single-stage administration regimen and the traditional three-stage regimen on fracture healing, and to preliminarily investigate their roles in activating the BMP/Smad signaling pathway. Methods A rat tibial fracture model was established and randomly divided into four groups: blank control, model control, single-stage treatment (administered a comprehensive formula throughout the experiment), and three-stage treatment (administered Fuyuan Huoxue decoction on days 1-7, Heying Zhitong decoction on days 8-28, and Jianbu Huqian Pill after day 28). Post-surgery, X-ray imaging was used to assess the degree of fracture healing. Levels of Calcium (Ca), Phosphorus (P), Alkaline Phosphatase (ALP), and Acid Phosphatase (ACP) were measured. Histological examination via HE staining was performed to observe callus tissue healing. Immunohistochemistry was used to detect the protein levels of BMP2, Runx2, and Smad1. RT-qPCR was employed to quantify the mRNA expression levels of BMP2, Runx2, and Smad1. Results Compared with the model control group, both the single-stage and three-stage treatment groups showed significantly accelerated fracture healing, with the single-stage group exhibiting the most pronounced effect. Alkaline phosphatase (ALP) levels in the model control group were (165±4.7)U/L. However, the single-stage administration and traditional three-stage regimen groups showed ALP levels of (233±12.2)U/L and (174±20.3)U/L, respectively. The significant elevation of ALP in the single-stage administration suggests that its effect on promoting fracture repair was markedly superior to both the model control group and the traditional three-stage regimen. The acid phosphatase (ACP) level in the single-stage administration was 0.192±0.027, which was significantly lower than that in the model control group (0.34±0.017) and the traditional three-stage regimen (0.265±0.014). Hematoxylin-eosin (HE) staining revealed a marked reduction in local inflammatory cell infiltration and abundant formation of cartilage and new bone in the single-stage administration; the traditional three-stage regimen also exhibited reduced inflammation and increased collagen/cartilage tissue. Immunohistochemical analysis showed that the expression level of Runx2 in the single-stage administration was 57.1±5.94, significantly higher than that in the model control group (41.6±3.11) and the traditional three-stage regimen (48.3±4.04). Levels of Smad and BMP2 were also elevated to varying degrees, and RT-PCR results further corroborated this finding. Conclusion The single-stage comprehensive treatment regimen effectively promotes fracture osteogenesis and remodeling by activating the BMP/Smad signaling pathway, and its effect is superior to the three-stage treatment approach.