目的 觀察傷科九味健骨片對骨折大鼠骨愈合的促進(jìn)作用及對TGF-β/Smad通路的調(diào)控機(jī)制。方法 制備SD大鼠右側(cè)脛骨閉合性骨折模型，按隨機(jī)數(shù)字表法分為模型組、傷科接骨片組和傷科九味健骨片低、高劑量組，每組8只，另取8只未經(jīng)處理的動物作為對照組。造模后第2天開始，傷科接骨片組ig傷科接骨片0.39 g/kg，傷科九味健骨片低、高劑量組分別ig傷科九味健骨片0.43、0.86 g/kg，對照組ig生理鹽水，1次/d，共28 d。解剖觀察右側(cè)脛骨骨折愈合情況和組織形態(tài)病理學(xué)情況；采用ELISA法檢測血清中促炎癥因子白細(xì)胞介素（IL）-1β、IL-6、腫瘤壞死因子-α（TNF-α）；以及骨形成因子堿性磷酸酶（ALP）、骨鈣素（BGP）的水平；利用Image J軟件進(jìn)行組織形態(tài)計量學(xué)分析Smad 1/5/9、Smad 6、轉(zhuǎn)化生長因子β（TGF-β）、骨形態(tài)發(fā)生蛋白2（BMP2）蛋白的表達(dá)。結(jié)果 傷科九味健骨片組大鼠骨折側(cè)脛骨愈合恢復(fù)良好，邊緣整齊，平滑無隆起，無明顯骨折痕跡；病理結(jié)果顯示，傷科九味健骨片組骨折側(cè)大鼠脛骨骨密質(zhì)結(jié)構(gòu)緊密，骨細(xì)胞及骨基質(zhì)形態(tài)正常，內(nèi)膜平整。與模型組比較，傷科九味健骨片能顯著降低骨折大鼠血清中IL-1β、IL-6、TNF-α水平，顯著升高骨折大鼠血清中ALP、BGP水平（P＜0.05、0.01）；并能顯著上調(diào)脛骨組織中BMP2、Smad 1/5/9、TGF-β蛋白的表達(dá)，下調(diào)Smad 6蛋白的表達(dá)（P＜0.05、0.01）。結(jié)論 傷科九味健骨片具有促進(jìn)骨折愈合的作用，其機(jī)制可能與降低血清中炎癥因子水平，升高骨形成因子水平，以及上調(diào)TGF-β、BMP2、Smad 1/5/9蛋白表達(dá)、下調(diào)Smad 6蛋白的表達(dá)有關(guān)。

Objective To observe the promoting effect of Shangke Jiuwei Jiangu Tablets on bone healing, and the regulatory mechanism of TGF-β/Smad pathway in fracture rats. Methods The model of closed fracture of the right tibia of SD rats was prepared, and the successfully constructed animals were divided into model group, Shangke Jiegu Tablets group, Shangke Jiuwei Jiangu Tablets low-dose and high-dose groups, with 8 animals in each group according to the random number table method, and 8 untreated animals were selected as control group. Starting from the second day after modeling, the Shangke Jiegu Tablets group was given 0.39 g/kg, the Shangke Jiuwei Jiangu Tablets low and the high-dose groups were given 0.43 and 0.86 g/kg Shangke Jiuwei Jiangu Tablets, respectively, and the control group was given normal saline, once daily for 28 d. The fracture union and histopathology of the right tibia were observed by anatomy. The pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and levels of bone forming factors ALP and BGP were detected by ELISA method. The expressions of Smad 1/5/9, Smad6, TGF-β, and BMP2 were analyzed by histomorphometric analysis using Image J software. Results The fracture-side tibia of the Shangke Jiuwei Jiangu Tablets group was well healed, with neat edges, smooth edges, and no obvious fracture traces. The pathological results showed that the tibial bone density structure was tight, the bone cells and bone matrix were normal and the intima was smooth in the Shangke Jiuwei Jiangu Tablets group. Compared with model group, Shangke Jiuwei Jiangu Tablets group could significantly reduce the levels of IL-1β, IL-6, and TNF-α in serum of fractured rats, and significantly increase the levels of ALP and BGP in serum of fractured rats (P < 0.05, 0.01). The expression of BMP2, Smad1/5/9, and TGF-β in tibia tissue was significantly up-regulated, while the expression of Smad 6 protein was down-regulated (P < 0.05, 0.01). Conclusion Shangke Jiuwei Jiangu Tablets has the effect of promoting fracture healing, and its mechanism may be related to reducing the level of inflammatory factors in serum, increasing the content of bone formation factors, up-regulating the expression of TGF-β, BMP2, Smad1/5/9 protein, and down-regulating the expression of Smad6 protein.

R285.5

廣東省中醫(yī)藥局科研項目（20212253）