沉默信息調節因子1調控成骨成血管功能促進頜骨缺損愈合的實驗研究

[中圖分類號]R782 [文獻標志碼] A[doi] 10.7518/gjkq.2025046

Promotionof mandibulardefect healing through the regulation of osteogenic and angiogenic functions bysirtuin1

LiuZhikai，LiuHanghang2，LiuShibo，LiBolun，LiuYao，Luo

1.StateKeyLaboratoryofOralDiseasesamp;National CenterforStomatologyamp;National ClinicalResearchCenter for OralDiseasesamp;Dept.ofOrthognathicandJointSurgery，WestChina HospitalofStomatologySichuan University Chengdu61o041，China；2.StateKeyLaboratoryofOral Diseasesamp;National CenterforStomatologyamp;National Clinical Research Center forOral Diseasesamp;Dept.ofEmergency，West China HospitalofStomatologySichuan University Chengdu 610041，China

Supportedby：NationalNaturalScienceFoundationofChina（8237o932）；KeyResearchandDevelopmentProjectofSi chuanProvince （2024YFFK0204）；Natural ScienceFoundation Youth ProjectofSichuan Province（2023NSFSC1512） Correspondence：Luo En，Email： luoen52l125@sina.com

[Abstract]ObjectiveThis studyaims to investigate the effectofsirtuin1（SIRT1）onosteogenic and angiogenic functions inmiceunder in vivoand in vitroconditions，aswellasitseffectonmandibulardefect healing.MethodsSIRT1activatorsand inhibitors wereused to intervene in MC3T3-E1cellsand mandibulardefects inmice.Various methods，includingcellcountingkit-8（CCK-8）assyreal-timequantitativepolymerasechainreaction，Westernblot，alkalinephos

phatase staining，and immunofluorescence staining，were employedtostudythe influenceofSIRT1 ontheexpression of osteogenic and angiogenic factors in MC3T3-E1 cells，aswell as the healing and osteogenic and angiogenic functions of mandibular defects in mice.Results Ininvitro experiments， the activation of SIRT1 promoted the expression of osteogenic and angiogenic factors

inMC3T3-E1cels.Ininvivoexperiments，SIRT1activationfacilitatedthehea-lingofmandibulardefectsandenhanced theosteogenicandangiogenic functionsofthe mandibular defects.Conversely，the inhibitionofSIRTl activitysuppressed the aforementioned processes.ConclusionSIRT1 can promote the healing of mandibular defects by regulating the osteogenic and angiogenic functions in mice.

[Key words] sirtuinl；angiogenesis；mandibular defect； bone regeneratior

頜骨缺損可由于頜面部的腫瘤、感染、外傷等多種疾病造成，目前臨床治療效果常不確切[]。骨缺損部位的新血管生成是骨愈合的關鍵因素，在缺損部位的血凝塊機化后，正常骨骼部位的血管產生新的血管生長進人缺損部位，該過程是整個骨愈合的始動環節[2。新生成的血管可以促進多種營養物質向新生骨組織中運輸從而促進骨愈合，已有研究表明骨組織內的血流不足會導致骨愈合較差。而在骨愈合早期局部應用促成血管因子可顯著促進骨缺損部位新骨生成，進一步表明了骨愈合過程中早期血管生成的重要性4。此外，成骨前體細胞、炎癥細胞等多種細胞同樣通過新生血管作為中間途徑到達骨損傷部位5。多種成骨及成血管因子在該過程中均有大量表達，如堿性磷酸酶（alkaline phosphatase，ALP）、Runt相關轉錄因子2（Runt-related transcription factor2，Runx2）、血管內皮生長因子（vascularendothelialgrowthfactor，VEGF）、Slit同源物3（Slithomolog3，Slit3）等。因此，骨再生與新血管生成過程存在密切偶聯，對該偶聯功能的調控可促進骨愈合進程。

Sirtuins是一個蛋白質分子家族，它們作為煙酰胺腺嘌呤二核苷酸（nicotinamideadeninedinu-cleotide，NAD）依賴性去乙?；竵碚{節基因組穩定性、能量穩態和應激信號的相關功能[67]。而沉默信息調節因子1（sirtuin1，SIRT1）則是該家族中研究最為廣泛的一種去乙?；?，在細胞核內，SIRT1通過促進組蛋白的去乙酰化和調節DNA的甲基化來控制染色質功能；在細胞質中，SIRT1參與調節多種細胞反應，如細胞自噬、內質網應激和線粒體應激等8。目前，已經發現SIRT1可以通過多種信號通路參與成骨細胞分化過程，同時SIRT1還參與調控體內新生血管形成及穩態[9]?！?br>