载青蒿琥酯的温敏壳聚糖水凝胶通过调节 2 型糖尿病大鼠 T 淋巴细胞促进上颌拔牙后骨再生。
Artesunate-loaded thermosensitive chitosan hydrogel promotes osteogenesis of maxillary tooth extraction through regulating T lymphocytes in type 2 diabetic rats.
机构信息
College & Hospital of Stomatology, Guangxi Medical University, No.10 Shuangyong Road, Nanning, Guangxi, 530021, China.
Medical Science Research Center, Guangxi Medical University, Nanning, Guangxi, 530021, China.
出版信息
BMC Oral Health. 2024 Mar 20;24(1):356. doi: 10.1186/s12903-024-04127-7.
BACKGROUND
Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats.
METHODS
T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored.
RESULTS
Results showed that the 150 mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p < 0.05). It also improved the expression of OPG, ALP, and RANK. Although the alteration of CD4 T, CD8 T, and CD4:CD8 T ratio has no significant difference among groups, the release of Th1 and Th2 in the 150 mg/ml ART-loaded TCH group has been significantly regulated than in the T2DM group (p < 0.05). Besides, ART-loaded TCH treatment inhibited the expression of p38 MAPK and ERK1 in T2DM maxilla.
CONCLUSIONS
Therefore, the results indicated that 150 mg/ml ART-loaded TCH could be an effective method to prevent bone loss in T2DM tooth extraction rats by modulating the immunoregulation of Th1 and Th2 and the MAPK signaling pathway.
背景
2 型糖尿病（T2DM）会导致拔牙后严重的骨质流失，因为高血糖环境会导致异常的骨稳态。青蒿琥酯（ART）具有抗炎和成骨特性。然而，其在牙槽骨中的成骨特性尚不清楚。本研究旨在探讨青蒿琥酯载热敏壳聚糖水凝胶（ART-载 TCH）对 T2DM 大鼠上颌拔牙后骨生成和免疫调节的影响。
方法
采用高脂饮食和链脲佐菌素诱导 T2DM 大鼠。将不同浓度的 ART-载 TCH 应用于拔牙窝。评估骨丢失和成骨调节因子（OPG、ALP、RANK）的表达。通过检测 T 淋巴细胞及其细胞因子的浸润来观察 ART-载 TCH 的免疫调节作用。并探讨其潜在机制。
结果
结果表明，与 T2DM 组相比，150mg/mlART-载 TCH 组上颌骨高度和骨密度明显改善（p<0.05）。它还改善了 OPG、ALP 和 RANK 的表达。虽然各组间 CD4T、CD8T 和 CD4:CD8T 比值的变化无显著差异，但 150mg/mlART-载 TCH 组 Th1 和 Th2 的释放明显受到调节，而 T2DM 组则无明显调节（p<0.05）。此外，ART-载 TCH 治疗抑制了 T2DM 上颌 p38MAPK 和 ERK1 的表达。
结论
因此，结果表明，150mg/mlART-载 TCH 可能通过调节 Th1 和 Th2 的免疫调节以及 MAPK 信号通路，成为预防 T2DM 拔牙后大鼠骨质流失的有效方法。
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