PINK1介导的线粒体自噬对牙周膜干细胞凋亡的保护机制

doi:10.13701/j.cnki.kqyxyj.2025.12.004

摘要/Abstract

摘要： 目的: 探讨PTEN诱导的激酶1(PTEN-induced kinase 1,PINK1)-Parkin介导的线粒体自噬在牙周炎微环境中的动态变化及其对牙周膜干细胞(periodontal ligament stem cells, PDLSCs)凋亡的调控作用。方法: 采用末端脱氧核苷酸转移酶介导的缺口末端标记法(terminal deoxynucleotidyl transferase dUTP nick end labeling,TUNEL)染色检测健康、牙龈炎及牙周炎患者牙龈组织的凋亡水平,免疫组织化学法评估PINK1与Parkin的表达。分离3组患者来源的PDLSCs,采用Western blot检测自噬、线粒体自噬及凋亡相关蛋白的表达。随后使用MitoTracker Red染色观察线粒体功能状态,并通过流式细胞术评估细胞凋亡水平。结果: 随着炎症加重,牙龈组织中凋亡细胞显著增多,PINK1与Parkin在牙龈炎组织中表达升高,在牙周炎组织中则表达下调。炎症来源的PDLSCs中,自噬相关蛋白Beclin-1表达上调,p62水平下降,提示自噬活性增强;PINK1/Parkin在牙龈炎组上调,在牙周炎组下调,反映线粒体自噬随炎症进程动态变化。MitoTracker Red染色结果显示,牙周炎组PDLSCs线粒体分布紊乱、荧光减弱,提示膜电位受损。Western blot与流式细胞术结果进一步表明,牙周炎组PDLSCs凋亡水平显著升高,表现为促凋亡信号增强、抗凋亡能力减弱。结论: 本研究结果揭示,线粒体自噬在牙周炎中的调控失衡可促发PDLSCs凋亡,提示其在疾病进展中的关键作用,亦可能为牙周组织再生提供潜在干预靶点。

关键词: 牙周炎, 牙龈炎, 线粒体自噬, 自噬, 凋亡, 牙周膜干细胞

Abstract: Objective: To investigate the dynamic changes of PTEN-induced kinase 1 (PINK1)-Parkin-mediated mitophagy under inflammatory conditions and its regulatory role in apoptosis of periodontal ligament stem cells (PDLSCs) during periodontitis progression. Methods: Apoptosis levels in gingival tissues from healthy individuals and patients with gingivitis or periodontitis were assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the expression of PINK1 and Parkin was evaluated by immunohistochemistry. PDLSCs were isolated from three groups, and the expressions of autophagy-related, mitophagy-related, and apoptosis-related proteins were analyzed by Western blotting. MitoTracker Red staining was used to examine mitochondrial function, and flow cytometry was performed to assess cell apoptosis. Results: With the progression of inflammation, apoptotic cells increased in gingival tissues. PINK1 and Parkin expression was upregulated in gingivitis tissues but downregulated in periodontitis. In PDLSCs derived from inflamed tissues, autophagy was enhanced, as evidenced by increased autophagy-related proteins and decreased p62 levels. The expression of PINK1 and Parkin showed a dynamic pattern consistent with mitophagy changes during disease progression. MitoTracker staining revealed disrupted mitochondrial distribution and reduced membrane potential in PDLSCs from the periodontitis group. Western blot and flow cytometry further confirmed elevated apoptosis, with strengthened pro-apoptotic signals and diminished anti-apoptotic activity. Conclusion: This study demonstrates that dysregulated mitophagy in periodontitis promotes PDLSC apoptosis, indicating that mitophagy plays a critical role in disease progression and may serve as a potential target for periodontal tissue regeneration.

Key words: periodontitis, gingivitis, mitophagy, autophagy, apoptosis, periodontal ligament stem cells

热甫卡提·地力毛拉提, 艾力麦尔旦·艾尼瓦尔, 王琪, 陈越, 哈丽娅. PINK1介导的线粒体自噬对牙周膜干细胞凋亡的保护机制[J]. 口腔医学研究, 2025, 41(12): 1037-1043.

Repukati·DILIMAOLATI, Ailimaierdan·AINIWAER, WANG Qi, CHEN Yue, HALIYA. Protective Mechanism of PINK1-mediated Mitophagy on Apoptosis of Periodontal Ligament Stem Cells[J]. Journal of Oral Science Research, 2025, 41(12): 1037-1043.

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