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吡格列酮可降低银屑病皮损中髓过氧化物酶和一氧化氮的水平:在咪喹莫特诱导的大鼠银屑病模型中的概念验证研究。

Pioglitazone attenuate level of myeloperoxidases and nitic oxide in psoriatic lesion: a proof-of-concept study in a imiquimod induced psoriasis model in rat.

机构信息

Division of Pharmacology, Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, India.

出版信息

J Basic Clin Physiol Pharmacol. 2024 Feb 12;35(1-2):45-52. doi: 10.1515/jbcpp-2023-0254. eCollection 2024 Jan 1.

Abstract

OBJECTIVES

Psoriasis is a persistent autoimmune inflammatory condition that is primarily affecting the skin. Pioglitazone (PGZ), a peroxisome proliferator activated receptor gamma (PPARγ) agonist, has been reported to have anti-inflammatory effects. However, the role of PGZ in psoriatic disease remains unclear. In this study, we aimed to repurpose the use of the PGZ for the treatment of psoriasis.

METHODS

To investigate its efficacy, we employed an imiquimod (IMQ)-induced rat model. Wistar rats are randomly allocated to four different groups. Group, I served as a negative control, Group II IMQ control, Group III was treated with pioglitazone hydrogel and Group IV received standard drug betamethasone cream. PASI score was monitored on every alternative day and on day 7 animals were sacrificed and histopathology of skin was performed. Level of nitric oxide (NO) and myeloperoxidase (MPO) was also performed using established methods.

RESULTS

The results of the experiment revealed that treatment with PGZ significantly (p<0.05) reduced redness, scaling, and skin thickening, surpassing the effectiveness of standard drugs. Our result also indicates that PGZ significantly (p<0.05) inhibits the release of both MPO and NO from the psoriatic lesions.

CONCLUSIONS

PGZ effectively reduces the severity of psoriasis possibly by inhibiting the accumulation of neutrophil at the psoriatic area which indirectly regulates the release of NO in the affected area. Our study showed we can repurpose the PGZ for the management of psoriasis.

摘要

目的

银屑病是一种持续性自身免疫性炎症性疾病,主要影响皮肤。吡格列酮(PGZ)是过氧化物酶体增殖物激活受体γ(PPARγ)激动剂,据报道具有抗炎作用。然而,PGZ 在银屑病中的作用尚不清楚。在这项研究中,我们旨在重新利用 PGZ 治疗银屑病。

方法

为了研究其疗效,我们采用咪喹莫特(IMQ)诱导的大鼠模型。Wistar 大鼠随机分为四组。第 I 组为阴性对照组,第 II 组为 IMQ 对照组,第 III 组给予吡格列酮水凝胶治疗,第 IV 组给予标准药物倍他米松乳膏治疗。每隔一天监测 PASI 评分,第 7 天处死动物并进行皮肤组织病理学检查。采用已建立的方法检测一氧化氮(NO)和髓过氧化物酶(MPO)的水平。

结果

实验结果表明,PGZ 治疗可显著(p<0.05)减轻红斑、鳞屑和皮肤增厚,疗效优于标准药物。我们的结果还表明,PGZ 可显著(p<0.05)抑制银屑病病变中 MPO 和 NO 的释放。

结论

PGZ 可有效减轻银屑病的严重程度,可能是通过抑制中性粒细胞在银屑病区域的积聚来间接调节受影响区域中 NO 的释放。我们的研究表明,我们可以重新利用 PGZ 来治疗银屑病。

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