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Tetramethylpyrazine (TMP) has been shown to exert lung\u2010protective effects in other pathological models, but its role in mitigating CIH\u2010induced 16HBE cell injury and the underlying molecular mechanisms have not been previously investigated. PTEN\u2010induced putative kinase 1 (PINK1)\u2010mediated mitophagy is a critical endogenous mechanism that defends against CIH\u2010induced epithelial damage. However, whether TMP alleviates CIH\u2010induced injury by regulating the PINK1 pathway remains unknown. CIH significantly reduced 16HBE cell viability, increased apoptosis rate, elevated inflammatory responses (IL\u20106 and TNF\u2010\u03b1 levels upregulated), and oxidative stress (ROS and MDA levels increased), and inhibited mitophagy (reduced PINK1 and LC3\u2010II\/LC3\u2010I ratio, increased p62). TMP treatment improved cell viability in a dose\u2010dependent manner; notably, 20\u2009\u03bcg\/mL TMP reversed CIH\u2010induced apoptosis, inflammation, and oxidative stress, accompanied by upregulated PINK1 and restored mitophagy. Moreover,\n                    <jats:italic>HDAC6<\/jats:italic>\n                    knockdown mimicked TMP's benefits (enhanced PINK1 and mitophagy, reduced injury), while concurrent\n                    <jats:italic>PINK1<\/jats:italic>\n                    silencing reversed this effect. TMP protected 16HBE cells from CIH\u2010induced injury by inhibiting HDAC6\u2010mediated PINK1 deacetylation. This mechanism stabilized PINK1 protein, enhanced mitophagy, and thereby suppressed apoptosis, oxidative stress, and inflammation, identifying the HDAC6\/PINK1 axis as a key regulatory pathway in CIH\u2010induced cell injury.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70236","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:03:57Z","timestamp":1768802637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tetramethylpyrazine Targets\n                    <scp>HDAC6<\/scp>\n                    \u2010Mediated\n                    <scp>PINK1<\/scp>\n                    Degradation to Alleviate Chronic Intermittent Hypoxia\u2010Induced Injury in Human Bronchial Epithelial Cells (\n                    <scp>16HBE<\/scp>\n                    )"],"prefix":"10.1111","volume":"107","author":[{"given":"Yanjie","family":"Chen","sequence":"first","affiliation":[{"name":"Department 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