Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 16, Issue 9, Pages 21775-21790Publisher
MDPI
DOI: 10.3390/ijms160921775
Keywords
tetramethylpyrazine; TR-iBRB2 cells; nitrosative stress; oxidative stress
Funding
- National Natural Science Foundation [81300787]
- Natural Science Foundation of Jiangsu Province [BK2012105, BK20141103]
- Major Project of Wuxi Municipal Health Bureau [ZS201401, Z201508]
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Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1 (IL-1) was reported to be involved in the induction of BRB breakdown during the pathogenesis of DR. In the present study, we investigated the protective effect of tetramethylpyrazine (TMP), a major active component of the traditional herb Ligusticum chuanxiong, on IL-1-induced cell death of the rat retinal capillary endothelial TR-iBRB2 cells. Our results showed that IL-1-induced cell dysfunction in TR-iBRB2 cells via inducing nitrative/oxidative stress; however, such effect was attenuated with the pre-treatment of TMP. The cellular protective effect of TMP was likely to be mediated through the inhibition of inducible nitric oxide synthase (iNOS) expression and leukostasis as well as suppression of reactive oxygen species (ROS) generation, mitochondrial dysfunction and MAPKs activation. These findings significantly contribute to a better understanding of the protective effect of TMP in DR and form the basis of the therapeutic development of TMP in treating such disease in the future.
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