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Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction

  • Authors:
    • Qing Xiao
    • Ya Yang
    • Xiao-Ya Zhao
    • Li‑Shan He
    • Yuan Qin
    • Yan‑Hua He
    • Gui‑Ping Zhang
    • Jian‑Dong Luo
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China, Guangzhou Research Institute of Snake Venom, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China
    Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1750-1758
    |
    Published online on: September 23, 2015
       https://doi.org/10.3892/etm.2015.2766
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Abstract

Our previous study demonstrated that an impaired sonic hedgehog (Shh) pathway contributed to cardiac dysfunction in type 1 diabetic mice with myocardial infarction (MI). The present study aimed to test the hypothesis that oxidative stress may contribute to the impaired Shh pathway and cardiac dysfunction in type 1 diabetic mice with MI. Streptozotocin‑induced type 1 diabetic mice (C57/Bl6, male) and rat neonatal cardiomyocytes were used in the present study. Mice were randomly assigned to undergo ligation of the coronary artery or pseudosurgery. A potent antioxidant Tempol was administered in vivo and in vitro. Cardiac function was assessed by echocardiography, capillary density by immunohistochemisty, percentage of myocardial infarct using Masson's trichrome staining, reactive oxygen species detection using dihydroethidium dye or 2',7'‑dichlorofluorescein diacetate probe and protein expression levels of the Shh pathway by western blot analysis. The antioxidant Tempol was shown to significantly increase myocardial protein expression levels of Shh and patched‑1 (Ptc1) at 7‑18 weeks and improved cardiac function at 18 weeks in type 1 diabetic mice, as compared with mice receiving no drug treatment. Furthermore, myocardial protein expression levels of Shh and Ptc1 were significantly upregulated on day 7 after MI, and capillary density was enhanced. In addition, the percentage area of myocardial infarct was reduced, and the cardiac dysfunction and survival rate were improved on day 21 in diabetic mice treated with Tempol. In vitro, treatment of rat neonatal cardiomyocytes with a mixture of xanthine oxidase and xanthine decreased protein expression levels of Shh and Ptc1 in a concentration‑dependent manner, and Tempol attenuated this effect. These results indicate that oxidative stress may contribute to an impaired Shh pathway in type 1 diabetic mice, leading to diminished myocardial healing and cardiac dysfunction. Antioxidative strategies aimed at restoring the endogenous Shh pathway may offer a useful means for improving diabetic cardiac function.
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Copy and paste a formatted citation
Spandidos Publications style
Xiao Q, Yang Y, Zhao X, He LS, Qin Y, He YH, Zhang GP and Luo JD: Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction . Exp Ther Med 10: 1750-1758, 2015.
APA
Xiao, Q., Yang, Y., Zhao, X., He, L., Qin, Y., He, Y. ... Luo, J. (2015). Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction . Experimental and Therapeutic Medicine, 10, 1750-1758. https://doi.org/10.3892/etm.2015.2766
MLA
Xiao, Q., Yang, Y., Zhao, X., He, L., Qin, Y., He, Y., Zhang, G., Luo, J."Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction ". Experimental and Therapeutic Medicine 10.5 (2015): 1750-1758.
Chicago
Xiao, Q., Yang, Y., Zhao, X., He, L., Qin, Y., He, Y., Zhang, G., Luo, J."Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction ". Experimental and Therapeutic Medicine 10, no. 5 (2015): 1750-1758. https://doi.org/10.3892/etm.2015.2766
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao Q, Yang Y, Zhao X, He LS, Qin Y, He YH, Zhang GP and Luo JD: Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction . Exp Ther Med 10: 1750-1758, 2015.
APA
Xiao, Q., Yang, Y., Zhao, X., He, L., Qin, Y., He, Y. ... Luo, J. (2015). Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction . Experimental and Therapeutic Medicine, 10, 1750-1758. https://doi.org/10.3892/etm.2015.2766
MLA
Xiao, Q., Yang, Y., Zhao, X., He, L., Qin, Y., He, Y., Zhang, G., Luo, J."Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction ". Experimental and Therapeutic Medicine 10.5 (2015): 1750-1758.
Chicago
Xiao, Q., Yang, Y., Zhao, X., He, L., Qin, Y., He, Y., Zhang, G., Luo, J."Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction ". Experimental and Therapeutic Medicine 10, no. 5 (2015): 1750-1758. https://doi.org/10.3892/etm.2015.2766
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