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Resveratrol Pretreatment Attenuates Cerebral Ischemic Injury by Upregulating Expression of Transcription Factor Nrf2 and HO-1 in Rats

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Abstract

Oxidative stress damage plays a vital role in cerebral ischemia/reperfusion (I/R) pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway can be activated by pharmacological and dietary means to attenuate cellular oxidative stress. Resveratrol, a plant-derived polyphenolic compound, has antioxidant property. Recent studies have demonstrated that resveratrol has protective effects against cerebral I/R injury. However, little is known about its mechanism. Hence, this study identified the neuroprotective effect of resveratrol pretreatment and elucidate the Nrf2/ARE signaling mechanism after focal cerebral I/R injury in rats. Adult male Sprague–Dawley rats were randomly assigned to sham-operated group, ischemia/reperfusion physiological saline-treated group, and ischemia/reperfusion resveratrol-pretreatmented (15 and 30 mg/kg) groups. Rats were pretreatmented with resveratrol or physiological saline of corresponding volume administered intraperitoneally for 7 days before surgery and 30 min before middle cerebral artery occlusion. At 24 h after reperfusion, neurological score, infarct volume, and brain water content were assessed. Oxidative stress was evaluated by malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Pathological changes of brain tissue were observed by HE staining. RT-PCR and Western blot analysed the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). TUNEL staining detected apoptotic cells. The protein expression of Caspase-3 were studied by immunohistochemistry. Resveratrol pretreatment significantly ameliorated neurological scores, reduced infarct volume and brain water content, decreased MDA levels, restored the SOD activity, upregulated the protein and mRNA expression of Nrf2 and HO-1, downregulated the protein expression of caspase-3. TUNEL-positive cells significantly decreased compared with the physiological saline-treated group. HE staining also showed that resveratrol significantly improved neuronal injury. These results showed that resveratrol pretreatment had neuroprotective effects on cerebral I/R injury. This neuroprotective effect is likely exerted by upregulated expression of transcription factor Nrf2 and HO-1 to ameliorate oxidative damage, decreased the protein expression of caspase-3. Our finding is important for understanding the neuroprotective mechanism of resveratrol and promoting its clinical therapeutic utility.

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Acknowledgments

This work was supported by grants from the National Nature Science Foundation of China (grant no. 81071119) and the Foundation for Science, Chongqing Bureau of Public Health (grant no. 2009-2-359).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China

    Junwei Ren, Cengceng Fan, Na Chen, Jiagui Huang & Qin Yang

  2. Department of Neurology, Chongqing Fuling Central Hospital, 2 Gaosuntang Road, Fuling District, Chongqing, 408000, China

    Junwei Ren

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  1. Junwei Ren
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  2. Cengceng Fan
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Correspondence to Qin Yang.

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Ren, J., Fan, C., Chen, N. et al. Resveratrol Pretreatment Attenuates Cerebral Ischemic Injury by Upregulating Expression of Transcription Factor Nrf2 and HO-1 in Rats. Neurochem Res 36, 2352–2362 (2011). https://doi.org/10.1007/s11064-011-0561-8

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