术前规律性运动可预防及缓解膝关节假体周围感染

doi:10.3877/cma.j.issn.2096-0263.2026.01.003

目的

探讨术前规律性运动对小鼠膝关节假体周围感染的预防和缓解作用。

方法

建立C57BL/6雄性小鼠膝关节PJI模型，将小鼠分为空白对照组、PJI组和术前规律性运动+PJI组。术前规律性运动+PJI组在PJI模型建立前进行为期6 w的跑台规律性运动干预。术后4 w，通过大体观察、X射线、Micro-CT、Giemsa染色、组织病理学染色（H&E、TRAP、Alcian blue、COL1A1免疫荧光）和qPCR检测，评估PJI的感染负荷、骨溶解、炎症反应及组织修复微环境。

结果

与PJI组相比，术前规律性运动+PJI组显著减轻了PJI的感染程度和细菌负荷，缓解了骨溶解（表现为骨膜反应减轻、破骨细胞数量减少、骨微结构参数如BMD、BV/TV等改善），降低了促炎因子（Il1b、Il6、Tnf、Cxcl15、Myd88、Tlr4）的表达水平，同时上调了抗炎因子（Il4、Il10）的表达，并减轻了局部组织炎症浸润和纤维化程度。

结论

术前规律性运动可通过减轻感染负荷、缓解骨溶解、控制炎症反应和改善组织修复微环境，有效缓解小鼠PJI的严重程度，为临床预防PJI提供了新的试验依据和潜在策略。

关键词: 术前规律性运动, 膝关节假体周围感染, 炎症反应, 骨溶解

Objective

To investigate the preventive and alleviating effects of preoperative regular exercise on periprosthetic knee joint infection in mice.

Methods

A knee periprosthetic joint infection (PJI) model was established in C57BL/6 male mice. The mice were divided into three groups: a blank control group, a PJI group, and a preoperative regular exercise + PJI group. The preoperative regular exercise + PJI group underwent a 6-week regular treadmill exercise intervention before the PJI model was established. Four weeks postoperatively, the infectious burden of PJI, osteolysis, inflammatory response, and the tissue repair microenvironment were assessed through gross observation, X-ray imaging, Micro-CT analysis, Giemsa staining, histopathological staining (H&E, TRAP, Alcian blue, COL1A1 immunofluorescence), and qPCR detection.

Results

Compared to the PJI group, preoperative regular exercise significantly reduced the severity of PJI and bacterial load, alleviated osteolysis (as evidenced by reduced periosteal reaction, decreased osteoclast numbers, and improved bone microarchitectural parameters such as BMD and BV/TV), decreased the expression levels of pro-inflammatory factors (Il1b, Il6, Tnf, Cxcl15, Myd88, Tlr4), while concurrently upregulating the expression of anti-inflammatory factors (Il4, Il10), and diminished local tissue inflammatory infiltration and the degree of fibrosis.

Conclusions

Preoperative regular exercise can effectively alleviate the severity of periprosthetic joint infection (PJI) in mice by reducing infectious burden, mitigating osteolysis, controlling the inflammatory response, and improving the tissue repair microenvironment. This provides new experimental evidence and potential strategies for the clinical prevention of PJI.

Key words: Preoperative regular exercise, Periprosthetic joint infection, Inflammatory response, Osteolysis

图1 术前规律性运动显著降低膝关节假体周围感染的细菌负荷及局部病变程度。（A）小鼠分为3组，分别为空白组（未感染）、PJI组（未运动后感染）、PJI+术前规律运动组（运动后感染），运动组小鼠在构建假体周围感染模型前，先在跑台上每天运动1 h，连续5 d运动，每周休息2 d，连续运动6 w，运动完休息1 d后构建PJI模型，待感染形成4 w后取材，对比三组小鼠的膝关节周围脓肿的大体观、X射线评估和Giemsa染色评估细菌负荷。（B）各组小鼠膝关节周围脓肿大小的半定量统计分析。数据以平均值±标准差（Mean ±SD）表示；每组样本量n=8；ns表示无统计学意义；***P<0.001（与Infe-CTRL组比较）。（C）各组小鼠感染膝关节的X射线影像学半定量评分。评分标准涵盖骨膜反应、骨干增宽、结构变形、软组织变形及新骨形成五个方面，每方面按0~4分（4分代表最严重）进行评分。数据以平均值±标准差表示；每组样本量n=8；ns表示无统计学意义；*** P<0.001（与Infe-CTRL组比较）。（D）各组小鼠膝关节周围软组织切片Giemsa染色后，每高倍视野下细菌数量的定量统计分析。数据以平均值±标准差表示；每组样本量n=8；ns表示无统计学意义；***P<0.001

图2 术前规律性运动有效缓解PJI诱导的骨溶解并保护骨微结构。（A）代表性图像：通过TRAP染色观察各组小鼠膝关节组织切片中破骨细胞的分布与数量（紫红色为TRAP阳性细胞），并通过微计算机断层扫描（Micro-CT）三维重建图像展示假体周围骨组织的骨溶解及骨膜反应情况。（B）各组小鼠膝关节组织切片TRAP染色后，每高倍视野下TRAP数量的定量统计分析。数据以平均值±标准差表示；每组样本量n=8；ns表示无统计学意义；*** P<0.001（与Infe-CTRL组比较）。（C-G）Micro-CT对各组小鼠股骨远端假体周围骨微结构参数的定量分析结果：（C）BMD；（D）BV/TV；（E）Tb.N；（F）Tb.Th；（G）Tb.Sp。所有数据均以平均值±标准差表示；每组样本量n=8；ns表示无统计学意义；** P<0.01；*** P<0.001

图3 通过qPCR检测各组小鼠膝关节假体周围软组织中炎症相关基因的mRNA相对表达水平。促炎因子表达水平的统计学分析包括：（A）IL1b；（B）IL6；（C）Tnf；（D）Cxcl15；（E）Myd88；（F）Tlr4。抗炎/抑炎因子表达水平的统计学分析包括：（G）IL4；（H）IL10；（I）IL17。所有数据均以平均值±标准差表示；每组样本量n=5；ns表示无统计学意义；* P<0.05；** P<0.01；*** P<0.001

图4 术前规律性运动改善PJI局部组织病理学改变并减轻组织纤维化，促进组织微环境修复。（A）代表性组织病理学染色图像：通过H&E染色观察各组小鼠膝关节周围软组织的炎症细胞浸润及组织结构变化；通过Alcian Blue染色评估膝关节周围软组织中酸性黏多糖（代表细胞外基质）的表达与分布情况；通过COL1A1免疫荧光染色评估膝关节周围组织的纤维化程度，其中DAPI（蓝色）复染细胞核，COL1A1阳性表达呈绿色荧光。（B）各组小鼠膝关节周围软组织Alcian Blue染色的半定量免疫组织化学评分。数据以平均值±标准差表示；每组样本量n=8；ns表示无统计学意义；*** P<0.001。（C）各组小鼠膝关节周围软组织COL1A1免疫荧光染色阳性面积的定量分析。数据以平均值±标准差表示；每组样本量n=8；ns表示无统计学意义；** P<0.01，*** P<0.001

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Preoperative regular exercise can prevent and mitigate knee periprosthetic joint infection

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Preoperative regular exercise can prevent and mitigate knee periprosthetic joint infection