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慢性牙周炎对大鼠阴茎海绵体内皮糖萼的影响。

Effect of chronic periodontitis on the endothelial glycocalyx of rat penile corpus cavernosum.

作者信息

Xia Yuanhang, Zeng Yang, Jiang Rui

机构信息

Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.

Department of Orthodontics, Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, China.

出版信息

Andrology. 2024 Sep 17. doi: 10.1111/andr.13765.

Abstract

BACKGROUND

Chronic periodontitis may induce erectile dysfunction (ED), however, the specific mechanism involved is unclear. The endothelial glycocalyx (eGlx) is a structure that can regulate endothelial nitric oxide synthase (eNOS) phosphorylation on the cavity surface of vessels.

AIM

To investigate whether chronic periodontitis leads to ED by affecting the eGlx.

METHODS

Twenty-four 4-week-old male Sprague‒Dawley rats were randomly divided into four groups (n = 6): the control group, chronic periodontitis group, chronic periodontitis + heparin group (subcutaneous heparin 200 U/kg/day, 7 days), and control + heparin group. Four weeks after the induction of periodontitis in the rats, the maximum intra-cavernous pressure/mean arterial pressure (ICPmax/MAP), serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), heparin sulfate (HS), syndecan-1 (SDC-1), heparanase (HPSE), eNOS, and phosphor-eNOS (p-eNOS) concentration were measured, and the eGlx of the penile corpus cavernosum was observed by transmission electron microscopy (TEM).

OUTCOMES

Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in the penile corpus cavernosum, and resulting in the inhibition of the erectile function.

RESULTS

Serum CRP, TNF-α, and IL-6 levels and HPSE expression in penile cavernous tissue were significantly greater in the chronic periodontitis group than in the control group and the chronic periodontitis + heparin group (P < 0.05). The average thickness of the eGlx muscle in the penile corpus cavernosum in the chronic periodontitis group was significantly lower than those in the control group and chronic periodontitis + heparin group (P < 0.05). The HS concentration, SDC-1 expression, p-eNOS/eNOS, NO concentration, and ICPmax/MAP in the chronic periodontitis group were significantly lower than those in the control group and chronic periodontitis+ heparin group (P < 0.01).

CLINICAL IMPLICATIONS

The eGlx on penile cavernosum vessels may be a new therapeutic target for the treatment of ED.

STRENGTHS AND LIMITATIONS

This study revealed that chronic periodontitis promotes the decomposition of vascular eGlx in the rat penile corpus cavernosum, however, it is not clear whether chronic periodontitis inhibits the synthesis of eGlx.

CONCLUSION

Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in penile cavernous tissue, and resulting in the inhibition of the erectile function. Heparin inhibited eGlx decomposition and improved erectile function in rats with chronic periodontitis.

摘要

背景

慢性牙周炎可能诱发勃起功能障碍(ED),但其具体机制尚不清楚。内皮糖萼(eGlx)是一种能在血管腔表面调节内皮型一氧化氮合酶(eNOS)磷酸化的结构。

目的

研究慢性牙周炎是否通过影响eGlx导致ED。

方法

将24只4周龄雄性Sprague-Dawley大鼠随机分为四组(n = 6):对照组、慢性牙周炎组、慢性牙周炎+肝素组(皮下注射肝素200 U/kg/天,共7天)和对照+肝素组。在大鼠诱发牙周炎4周后,测量海绵体内最大压力/平均动脉压(ICPmax/MAP)、血清C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、一氧化氮(NO)、硫酸乙酰肝素(HS)、多配体蛋白聚糖-1(SDC-1)、乙酰肝素酶(HPSE)、eNOS和磷酸化eNOS(p-eNOS)的浓度,并通过透射电子显微镜(TEM)观察阴茎海绵体的eGlx。

结果

慢性牙周炎可通过提高血清CRP、TNF-α和IL-6水平,降低p-eNOS/eNOS比值以及阴茎海绵体内的NO浓度,导致大鼠阴茎海绵体eGlx降解,进而抑制勃起功能。

结果

慢性牙周炎组血清CRP、TNF-α和IL-6水平以及阴茎海绵体组织中HPSE的表达显著高于对照组和慢性牙周炎+肝素组(P < 0.05)。慢性牙周炎组阴茎海绵体中eGlx肌肉的平均厚度显著低于对照组和慢性牙周炎+肝素组(P < 0.05)。慢性牙周炎组的HS浓度、SDC-1表达、p-eNOS/eNOS、NO浓度和ICPmax/MAP显著低于对照组和慢性牙周炎+肝素组(P < 0.01)。

临床意义

阴茎海绵体血管上 的eGlx可能是治疗ED的新靶点。

优点和局限性

本研究揭示了慢性牙周炎促进大鼠阴茎海绵体血管eGlx的分解,但尚不清楚慢性牙周炎是否抑制eGlx的合成。

结论

慢性牙周炎可通过提高血清CRP、TNF-α和IL-6水平,降低p-eNOS/eNOS比值以及阴茎海绵体组织中的NO浓度,导致大鼠阴茎海绵体eGlx降解,进而抑制勃起功能。肝素可抑制慢性牙周炎大鼠的eGlx分解并改善勃起功能。

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