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缺血/再灌注胃模型中HIF-1α和诱导型一氧化氮合酶的评估:生物阻抗、组织学和免疫组织化学分析

Evaluation of HIF-1α and iNOS in ischemia/reperfusion gastric model: bioimpedance, histological and immunohistochemical analyses.

作者信息

Peña-Mercado Eduardo, Garcia-Lorenzana Mario, Arechaga-Ocampo Elena, González-De la Rosa Claudia H, Beltran Nohra E

机构信息

Postgraduate Graduate Program, Natural Sciences and Engineering Division, Universidad Autonoma Metropolitana, Cuajimalpa, Mexico City, Mexico.

Department of Reproduction Biology, Universidad Autonoma Metropolitana, Iztapalapa, Mexico City, Mexico.

出版信息

Histol Histopathol. 2018 Aug;33(8):815-823. doi: 10.14670/HH-11-975. Epub 2018 Feb 16.

Abstract

UNLABELLED

Gastrointestinal ischemia/reperfusion (I/R) generates pathological alterations that could lead to death. Early ischemic damage markers could be used to guide therapy and improve outcomes.

AIM

To relate hypoxia-inducible factor 1α (HIF-1α) activation and inducible nitric oxide synthase (iNOS) expression to gastric impedance changes due to I/R damage.

METHODS

Experimental animals were randomly distributed into 3 groups: control, ischemia (30 min) and I/R (60 min). Gastric ischemia was generated by celiac artery clamping for 30 min, and then blood flow was restored for 60 min. Impedance spectra and biopsies of the glandular portion were obtained for histological and immunohistochemical analyses. Immunodetection of both HIF-1α and iNOS was performed.

RESULTS

Under ischemia and I/R conditions, there was an increase (p<0.05) in the impedance parameters. Histologically, under ischemic conditions, edema and necrosis were observed in epithelium and significant vascular congestion. In I/R condition, alterations of the glandular and luminal integrity were found, which generated areas of epithelial erosion. Immunohistochemical analysis of HIF-1α revealed an increase (p<0.01) in the number of immunoreactive cells in the ischemia (35.7±13.9) and I/R (119.9±18.8) conditions compared to the control (0.8±1.2). Immunodetection of iNOS showed an increase (p<0.01) in the number of cells expressing iNOS under the ischemia (5.4±2.9) and I/R conditions (27.4±11.3) was observed compared to the control (0.4±0.8).

CONCLUSION

Early changes in impedance in response to I/R is related to histopathological changes, the nuclear stabilization and translocation of HIF-1α as well as expression of iNOS.

摘要

未标记

胃肠道缺血/再灌注(I/R)会产生可能导致死亡的病理改变。早期缺血损伤标志物可用于指导治疗并改善预后。

目的

探讨缺氧诱导因子1α(HIF-1α)激活和诱导型一氧化氮合酶(iNOS)表达与I/R损伤所致胃阻抗变化的关系。

方法

将实验动物随机分为3组:对照组、缺血组(30分钟)和I/R组(60分钟)。通过夹闭腹腔动脉30分钟造成胃缺血,然后恢复血流60分钟。获取阻抗谱并对腺部进行活检,用于组织学和免疫组织化学分析。进行HIF-1α和iNOS的免疫检测。

结果

在缺血和I/R条件下,阻抗参数增加(p<0.05)。组织学上,在缺血条件下,上皮出现水肿和坏死,血管明显充血。在I/R条件下,发现腺管和管腔完整性改变,产生上皮糜烂区域。与对照组(0.8±1.2)相比,HIF-1α的免疫组织化学分析显示,缺血组(35.7±13.9)和I/R组(119.9±18.8)中免疫反应性细胞数量增加(p<0.01)。iNOS的免疫检测显示,与对照组(0.4±0.8)相比,缺血组(5.4±2.9)和I/R条件下(27.4±11.3)表达iNOS的细胞数量增加(p<0.01)。

结论

I/R引起的阻抗早期变化与组织病理学变化、HIF-1α的核稳定和转位以及iNOS的表达有关。

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