Zhu Xue, Wang Ke, Zhang Kai, Tan Xuhua, Wu Zhifeng, Sun Song, Zhou Fanfan, Zhu Ling
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Department of Ophthalmology, Wuxi No. 2 People's Hospital, Nanjing Medical University, Wuxi 214002, China.
Int J Mol Sci. 2015 Sep 9;16(9):21775-90. doi: 10.3390/ijms160921775.
Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1β (IL-1β) 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-1β-induced cell death of the rat retinal capillary endothelial TR-iBRB2 cells. Our results showed that IL-1β-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.
血视网膜屏障（BRB）破坏是糖尿病视网膜病变（DR）的主要原因之一。据报道，促炎因子白细胞介素-1β（IL-1β）在DR发病机制中参与诱导BRB破坏。在本研究中，我们研究了传统草药川芎的主要活性成分川芎嗪（TMP）对IL-1β诱导的大鼠视网膜毛细血管内皮TR-iBRB2细胞死亡的保护作用。我们的结果表明，IL-1β通过诱导硝化/氧化应激导致TR-iBRB2细胞功能障碍；然而，TMP预处理可减弱这种作用。TMP的细胞保护作用可能是通过抑制诱导型一氧化氮合酶（iNOS）表达和白细胞淤滞以及抑制活性氧（ROS）生成、线粒体功能障碍和丝裂原活化蛋白激酶（MAPKs）激活来介导的。这些发现显著有助于更好地理解TMP在DR中的保护作用，并为未来TMP治疗此类疾病的治疗发展奠定基础。
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