慢性间歇性缺氧对大鼠茎突舌肌的影响及作用机制

The effects of chronic intermittent hypoxia on the styloglossus muscle in rats and its mechanism of action

摘要

目的 探讨慢性间歇性缺氧(chronic intermittent hypoxia, CIH)对大鼠茎突舌肌形态结构及收缩功能相关蛋白表达的影响，并分析血清素(5-hydroxytryptamide, 5-HT)在其中的调控作用。方法 将30只雄性SD大鼠随机分为常氧对照组和CIH组；CIH组进一步分为3周(3wCIH)、5周(5wCIH)及8周(8wCIH)暴露组。于相应时间点取茎突舌肌组织，采用苏木精-伊红(hematoxylin-eosin, HE)染色观察其形态结构，免疫组织化学法检测5-HT、5-HT 2A受体、兰尼碱受体(ryanodine receptor, RYR)及肌浆网钙ATP酶(sarcoendoplasmic reticulum Ca²⁺-transporting ATPase, SERCA)蛋白表达水平。结果 与对照组相比，各CIH组大鼠茎突舌肌出现肌纤维排列紊乱、间距增大及细胞核分布杂乱等形态学改变，且损伤程度随缺氧时间延长而加重。免疫组织化学结果显示，与对照组相比，3wCIH组5-HT(P<0.01)及5-HT 2A受体(P<0.05)表达上调，且高于5wCIH与8wCIH组，差异有统计学意义(P<0.001)；各CIH组(3wCIH、5wCIH、8wCIH)的RYR表达量随时间呈持续下降趋势，差异有统计学意义(P<0.05)；SERCA表达量在5wCIH组和8wCIH组降低，差异有统计学意义(P<0.01)，总体呈时间依赖性下降趋势。结论 长期CIH可导致茎突舌肌结构损伤，伴随5-HT能神经调控的代偿机制失效以及钙调控蛋白表达下调，最终引起收缩功能受损。

Abstract

Objective To investigate the effects of chronic intermittent hypoxia (CIH) on the morphological structure and expression of contraction-related proteins in the styloglossus muscle of rats, and to analyze the regulatory role of serotonin (5-hydroxytryptamide, 5-HT) in this process. Methods Thirty male Sprague Dawley (SD) rats were randomly divided into a normoxic control group and a CIH group, which was further subdivided into 3-week (3wCIH), 5-week (5wCIH), and 8-week (8wCIH) exposure groups. At the respective time points, styloglossus muscle tissues were collected, hematoxylin-eosin (HE) staining was used to observe their morphological structure, and immunohistochemistry was employed to detect the protein expression levels of 5-HT, 5-HT 2A receptor, ryanodine receptor (RYR), and sarcoplasmic reticulum Ca ²⁺-transporting ATPase (SERCA). Results Compared with the control group, the rats in each CIH group exhibited morphological changes in the styloglossus muscle, such as disordered muscle fiber arrangement, increased spacing, and chaotic distribution of cell nuclei, with the severity of damage increasing with prolonged hypoxia. Immunohistochemical results showed that compared with the control group, the expression of 5-HT (P<0.01) and 5-HT 2A receptor (P<0.05) was upregulated in the 3wCIH group, and was higher than that in the 5wCIH and 8wCIH groups, with statistically significant differences (P<0.001). The expression of RYR in each CIH group (3wCIH, 5wCIH, 8wCIH) showed a continuous downward trend over time, with statistically significant differences (P<0.05). The expression of SERCA decreased in the 5wCIH and 8wCIH groups, with statistically significant differences (P<0.01), showing an overall time-dependent downward trend. Conclusion Long-term CIH can lead to structural damage to the styloglossus muscle, accompanied by the failure of the compensatory mechanism regulated by 5-HTergic nerves and downregulation of calcium-regulatory protein expression, ultimately causing impaired contraction function.

关键词

慢性间歇性缺氧 / 茎突舌肌 / 血清素

Key words

Chronic intermittent hypoxia / Styloglossus muscle / 5-hydroxytryptamide

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