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李-ESWT 治疗通过 PI3K/AKT/FOXO1 通路减轻自身免疫性前列腺炎大鼠模型中的炎症、氧化应激和疼痛。

Li-ESWT treatment reduces inflammation, oxidative stress, and pain via the PI3K/AKT/FOXO1 pathway in autoimmune prostatitis rat models.

机构信息

Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Lanzhou University Second Hospital, Lanzhou, China.

Department of Urology, Gansu Provincial Hospital, Lanzhou, China.

出版信息

Andrology. 2021 Sep;9(5):1593-1602. doi: 10.1111/andr.13027. Epub 2021 Sep 8.

Abstract

BACKGROUND

Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated.

OBJECTIVE

To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS.

MATERIALS AND METHODS

According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li-ESWT group (LPS-induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis.

RESULTS

Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1β, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all p < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both p < 0.05). Moreover, the Li-ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway.

DISCUSSION AND CONCLUSIONS

Li-ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity-induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.

摘要

背景

由于慢性前列腺炎/慢性骨盆疼痛综合征(CP/CPPS)发病机制的数据有限,以及治疗效果不理想,因此迫切需要开发新的有效治疗方法。低强度体外冲击波疗法(Li-ESWT)已被报道可用于治疗 CP/CPPS。然而,其潜在机制仍有待阐明。

目的

探讨 Li-ESWT 治疗 CP/CPPS 的疗效及机制。

材料和方法

根据不同的治疗方法,将 RWPE-1 细胞(人前列腺上皮细胞)随机分为三组:对照组、LPS(脂多糖)组或 Li-ESWT 组(LPS 诱导的 RWPE-1 采用 Li-ESWT 处理)。Li-ESWT 治疗后,检测氧化应激水平。然后,我们通过注射前列腺蛋白匀浆与完全弗氏佐剂混合,建立实验性自身免疫性前列腺炎(EAP)大鼠模型。将 Sprague-Dawley 大鼠随机分为对照组、EAP 组或 Li-ESWT 组。使用 Von Frey 细丝定量评估大鼠的骨盆痛觉过敏。收集各组前列腺组织进行免疫组织化学、氧化应激和 Western blot 分析。

结果

组织学分析显示,与 EAP 组相比,Li-ESWT 组前列腺组织中的炎症和细胞因子(TNF-α、IL-1β、IL-6、COX-2、SP)表达减少(均 p<0.05)。同样,与 EAP 组相比,Li-ESWT 组的骨盆疼痛和过敏症状减轻(均 p<0.05)。此外,Li-ESWT 治疗可分别降低前列腺和 RWPE-1 细胞中的氧化应激(均 p<0.05)。此外,Li-ESWT 通过抑制 AKT/FOXO1 信号通路的磷酸化来上调 CAT 的表达。

讨论和结论

Li-ESWT 可能通过 PI3 K/AKT/FOXO1 通路减轻自身免疫性前列腺炎大鼠的炎症、氧化应激和疼痛。这表明 Li-ESWT 可为 CP/CPPS 的治疗提供一种潜在的治疗选择。

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