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蜂毒素对完全弗氏佐剂诱导的大鼠慢性前列腺炎模型的治疗作用。

Therapeutic effect of melittin on a rat model of chronic prostatitis induced by Complete Freund's Adjuvant.

机构信息

Department of Emergency Medicine, Wuhan No.1 Hospital, Wuhan, China.

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

Biomed Pharmacother. 2017 Jun;90:921-927. doi: 10.1016/j.biopha.2017.04.055. Epub 2017 Apr 22.

Abstract

OBJECTIVES

The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model.

METHODS

Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression.

CONCLUSION

Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS.

摘要

目的

本研究旨在建立一种大鼠慢性前列腺炎模型,方法是向前列腺内注射完全弗氏佐剂(CFA),并研究蜂毒素对新开发的慢性前列腺痛模型的抗炎和镇痛作用。

方法

成年雄性 Sprague-Dawley 大鼠向前列腺内注射 CFA。在治疗组大鼠前列腺内注射蜂毒素 12 天后,对照组大鼠接受无菌生理盐水注射。在 CFA 注射当天以及 CFA 注射后 6、12 和 18 天,使用行为方法(即机械疼痛阈值测量)评估 CFA 的痛觉效应。在活体研究后,收集前列腺进行炎症细胞浸润的组织学检查。使用免疫组织化学法测定前列腺中环氧化酶(COX)-2 和脊髓中胶质纤维酸性蛋白(GFAP)的水平。假手术对照组大鼠接受前列腺内无菌生理盐水注射,并使用相同方法进行研究。

结果

前列腺内 CFA 注射引起局部痛觉过敏,持续至少 2 周。大鼠的疼痛行为与前列腺内炎症细胞浸润增加有关。前列腺中的 COX-2 水平和脊髓中的 GFAP 水平也升高。蜂毒素治疗显著提高疼痛阈值,减少炎症浸润,并抑制 COX-2 和 GFAP 的表达。

结论

前列腺内注射 CFA 可诱导神经原性前列腺炎和前列腺痛。所建立的模型将有助于 CP/CPPS 发病机制的研究。蜂毒素对慢性前列腺痛模型表现出显著的抗炎和镇痛作用,表明蜂毒素可能有希望成为治疗 CP/CPPS 的新疗法。

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