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Abstract：
UNASSIGNED: A multitude of variables influence the healing of tooth extraction wounds, and delayed or non-healing extraction wounds might complicate later prosthodontic therapy. In this research, we analyzed the effects of systemic clopidogrel and aspirin alone or in combination on the healing of tooth extraction wounds in mice in order to provide experimental evidence for the healing of extraction wounds in patients who are clinically treated with the two medicines.
UNASSIGNED: 7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1 week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10 mg/kg/d), aspirin (15 mg/kg/d), clopidogrel (10 mg/kg/d)+aspirin (15 mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28 days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin).
UNASSIGNED: MicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05).
UNASSIGNED: Clopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.
UNASSIGNED: 7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1 week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10 mg/kg/d), aspirin (15 mg/kg/d), clopidogrel (10 mg/kg/d)+aspirin (15 mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28 days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin).
UNASSIGNED: MicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05).
UNASSIGNED: Clopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.
摘要：
■许多变量会影响拔牙伤口的愈合，延迟或不愈合的拔牙伤口可能会使以后的修复治疗复杂化。在这项研究中,我们分析了氯吡格雷和阿司匹林单独或联合使用对小鼠拔牙创面愈合的影响，为临床使用这两种药物治疗的患者拔牙创面的愈合提供实验依据。
■7周龄ICR小鼠随机分为4组:对照组(CON),氯吡格雷组（CLOP），阿司匹林组（ASP），氯吡格雷联合阿司匹林组（CLOP+ASP）；拔除左上第一磨牙，之后，小鼠在1周的适应性喂养，CLOP/ASP/CLOP+ASP组分别给予氯吡格雷(10mg/kg/d),阿司匹林（15mg/kg/d），氯吡格雷（10mg/kg/d）+阿司匹林（15mg/kg/d），对照组给予等量的0.9%生理盐水灌胃。每组小鼠在术后14天和28天安乐死，上颌骨被拔除.用MicroCT检查拔牙窝内的组织，并切片进行HE染色，Masson染色,和TRAP染色，和免疫组织化学染色(对于TRAP，RANKL和骨保护素)。
■MicroCT分析表明，在第14天，与对照组和ASP组相比，CLOP和CLOPASP组的BS/BV显着降低，而BV/TV,TB。Th显著较高。在第28天，CLOP+ASP组的BV/TV显著高于CLOP组，所有结果的p<0.05。HE染色和Masson三色染色结果显示，在第28天，与第14天相比，骨骼中的间质进一步减少，并伴有紧密排列和相互联系的骨小梁。在对Masson的定量分析中,与CON组相比，CLOP组新形成的胶原蛋白含量显着升高（p<0.05）。在第14天，ASP组的TRAP阳性细胞明显多于CLOP和CLOP+ASP组（p<0.05）。在免疫组织化学染色中，发现在第28天，ASP组RANKL表达明显高于其他三组（p<0.05）；CLOP组和CLOPASP组OPG表达明显高于第14天，在第14天和第28天高于ASP组。CLOP和CLOP+ASP组的OPG/RANKL显著高于ASP组(p<0.05)。
■单独使用氯吡格雷可促进拔牙伤口的成骨，而阿司匹林单独抑制牙槽骨愈合。当两种药物混合使用时，拔牙创面的愈合效果与单独使用氯吡格雷组更为相似。这些结果表明，氯吡格雷可以促进拔牙伤口的愈合，并中和两种药物联合使用时ASP对成骨的不利影响。
■7周龄ICR小鼠随机分为4组:对照组(CON),氯吡格雷组（CLOP），阿司匹林组（ASP），氯吡格雷联合阿司匹林组（CLOP+ASP）；拔除左上第一磨牙，之后，小鼠在1周的适应性喂养，CLOP/ASP/CLOP+ASP组分别给予氯吡格雷(10mg/kg/d),阿司匹林（15mg/kg/d），氯吡格雷（10mg/kg/d）+阿司匹林（15mg/kg/d），对照组给予等量的0.9%生理盐水灌胃。每组小鼠在术后14天和28天安乐死，上颌骨被拔除.用MicroCT检查拔牙窝内的组织，并切片进行HE染色，Masson染色,和TRAP染色，和免疫组织化学染色(对于TRAP，RANKL和骨保护素)。
■MicroCT分析表明，在第14天，与对照组和ASP组相比，CLOP和CLOPASP组的BS/BV显着降低，而BV/TV,TB。Th显著较高。在第28天，CLOP+ASP组的BV/TV显著高于CLOP组，所有结果的p<0.05。HE染色和Masson三色染色结果显示，在第28天，与第14天相比，骨骼中的间质进一步减少，并伴有紧密排列和相互联系的骨小梁。在对Masson的定量分析中,与CON组相比，CLOP组新形成的胶原蛋白含量显着升高（p<0.05）。在第14天，ASP组的TRAP阳性细胞明显多于CLOP和CLOP+ASP组（p<0.05）。在免疫组织化学染色中，发现在第28天，ASP组RANKL表达明显高于其他三组（p<0.05）；CLOP组和CLOPASP组OPG表达明显高于第14天，在第14天和第28天高于ASP组。CLOP和CLOP+ASP组的OPG/RANKL显著高于ASP组(p<0.05)。
■单独使用氯吡格雷可促进拔牙伤口的成骨，而阿司匹林单独抑制牙槽骨愈合。当两种药物混合使用时，拔牙创面的愈合效果与单独使用氯吡格雷组更为相似。这些结果表明，氯吡格雷可以促进拔牙伤口的愈合，并中和两种药物联合使用时ASP对成骨的不利影响。
