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吡格列酮通过调节过氧化物酶体增殖物激活受体γ和血红素加氧酶 1 对雌性大鼠卵巢缺血再灌注损伤的保护作用。

Protective effect of pioglitazone on ovarian ischemia reperfusion injury of female rats via modulation of peroxisome proliferator activated receptor gamma and heme-oxygenase 1.

机构信息

Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt.

出版信息

Int Immunopharmacol. 2018 Sep;62:7-14. doi: 10.1016/j.intimp.2018.06.037. Epub 2018 Jun 29.

DOI:10.1016/j.intimp.2018.06.037
PMID:29966944
Abstract

Ovarian torsion is a dangerous gynecological emergency condition. Early diagnosis of this case is necessary to preserve the function of the ovaries and fallopian tubes and prevent further damage. Ovarian torsion means complete or partial rotation of the adnexa with ischemia followed by reperfusion period. Ovarian torsion affects 2%-15% of patients who have surgical treatment of adnexal masses. We investigated the effect of pioglitazone (PIO) on induced ovarian ischemia reperfusion (OIR). PIO (10, 30 mg/kg) was administered orally in the presence or absence of induced OIR. We measured ovarian tissue malondialdehyde (MDA), total nitrites (NO), reduced glutathione (GSH), heme-oxygenase 1 (HO-1), and gene expressions of peroxisome proliferator activated receptor gamma (PPARγ), tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Moreover, expression of p53 and histopathological changes were also evaluated. Results showed increase in the ovarian tissue levels of MDA and NO and gene expressions of p53, TNFα, and iNOS in the induced OIR group. The induced OIR group showed the histopathological changes associated with cell injury, marked ovarian edema, hemorrhage and congestion. In addition, there was reduction in the GSH, HO-1 levels and PPARγ, eNOS gene expressions. PIO was able to reduce these induced OIR changes to levels insignificant from control group. This protective effect of PIO may be attributed to its PPARγ agonist effect, anti-inflammatory, anti-apoptotic and anti-oxidant properties.

摘要

卵巢扭转是一种危险的妇科急症。早期诊断对于保留卵巢和输卵管的功能以及防止进一步损伤至关重要。卵巢扭转是指附件的完全或部分旋转伴有缺血,随后是再灌注期。卵巢扭转影响接受附件肿块手术治疗的患者的 2%-15%。我们研究了吡格列酮 (PIO) 对诱导性卵巢缺血再灌注 (OIR) 的影响。PIO(10、30mg/kg) 口服给药,存在或不存在诱导性 OIR。我们测量了卵巢组织丙二醛 (MDA)、总亚硝酸盐 (NO)、还原型谷胱甘肽 (GSH)、血红素加氧酶 1 (HO-1)、过氧化物酶体增殖物激活受体 γ (PPARγ)、肿瘤坏死因子-α (TNFα)、诱导型一氧化氮合酶 (iNOS) 和内皮型一氧化氮合酶 (eNOS) 的基因表达。此外,还评估了 p53 的表达和组织病理学变化。结果显示,诱导性 OIR 组卵巢组织 MDA 和 NO 水平以及 p53、TNFα 和 iNOS 基因表达增加。诱导性 OIR 组表现出与细胞损伤相关的组织病理学变化,卵巢明显水肿、出血和充血。此外,GSH、HO-1 水平和 PPARγ、eNOS 基因表达降低。PIO 能够将这些诱导性 OIR 变化降低到与对照组无显著差异的水平。PIO 的这种保护作用可能归因于其作为 PPARγ 激动剂的作用、抗炎、抗凋亡和抗氧化特性。

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