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The regulation of retinoid X receptor-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury / 生理学报
Acta Physiologica Sinica ; (6): 301-310, 2019.
Article in Chinese | WPRIM | ID: wpr-777185
ABSTRACT
The aim of this study was to investigate the regulatory role of retinoid X receptor (RXR)-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury (PIRI) and the underlying mechanism. Seventy-seven male Sprague-Dawley (SD) rats were randomly divided into 7 groups (n = 11) control group, sham group, sham+9-cis-retinoid acid (9-cRA, RXR agonist) group, sham+HX531 (RXR inhibitor) group, ischemia/reperfusion (I/R) group, I/R+9-cRA group, and I/R+HX531 group. The unilateral lung I/R model was established by obstruction of left lung hilus for 30 min and reperfusion for 180 min in vivo. The rats in I/R+9-cRA and I/R+HX531 groups were given intraperitoneal injection of 9-cRA and HX531 before thoracotomy. After reperfusion, the left lung tissue was taken to evaluate the lung tissue injury, and the oxidative stress-related indexes of the lung tissue were detected by the corresponding kits. The lung tissue morphology and the ultrastructure of the alveolar epithelial cells were observed by HE staining and transmission electron microscope, respectively. The protein expression of RXR in lung tissue was observed by immunofluorescence labeling method, and the expression level of nuclear factor E2-related factor (Nrf2) protein was detected by Western blot. The results showed that, compared with the sham group, the I/R group exhibited obviously injured lung tissue, decreased SOD activity, increased MDA content and MPO activity, and down-regulated expression level of Nrf2 protein. Compared with the I/R group, the I/R+9-cRA group showed alleviated lung tissue injury, increased activity of SOD, decreased MDA content and MPO activity, and up-regulated expression levels of RXR and Nrf2 protein. The above-mentioned improvement effects of 9-cRA were reversed by HX531 treatment. These results suggest that RXR activation can effectively protect the lung tissue against I/R injury, and the mechanism may involve the activation of Nrf2 signaling pathway, the enhancement of antioxidant level and the reduction of oxidative stress response.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Physiology / Reperfusion Injury / Signal Transduction / Random Allocation / Rats, Sprague-Dawley / Oxidative Stress / Retinoid X Receptors / NF-E2-Related Factor 2 / Lung Type of study: Prognostic study Limits: Animals Language: Chinese Journal: Acta Physiologica Sinica Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Physiology / Reperfusion Injury / Signal Transduction / Random Allocation / Rats, Sprague-Dawley / Oxidative Stress / Retinoid X Receptors / NF-E2-Related Factor 2 / Lung Type of study: Prognostic study Limits: Animals Language: Chinese Journal: Acta Physiologica Sinica Year: 2019 Type: Article