Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Biotech Center for Viral Disease Emergency, National Institute for Disease Control and Prevention, Chinese Disease Control and Prevention, Beijing, China.
Drug Dev Res. 2019 Jun;80(4):446-452. doi: 10.1002/ddr.21516. Epub 2019 Feb 4.
Sitagliptin (Sita) is a dipeptidyl peptidase-4 inhibitor which has been approved as a curing medicine for Type 2 diabetes (T2D) and has also reported its neuroprotective and antioxidant activity. This article describes the therapeutic effects of Sita on induced rat model of SE by kainic acid (KA) and investigated the antioxidative pathway of sita.
Sprague-Dawley male rats were used randomly divided in four groups: vehicle control, KA and Sita + KA in a 5 and 10 mg/kg doses respectively in further groups. SE in rats was induced by the administration of KA in Phosphate buffered saline (PBS) intraperitoneally (IP) in a dose of 15 mg/kg. Seizure intensity, oxidative stress parameters, TUNEL assay, histopathology, and Nrf2/HO-1 expressions were evaluated.
Increment in the latency in SE results in delaying the initiation of disease in the pretreated rats by Sita compared to induce group (KA) as well the percentage of occurrence of SE was decreased. The content of MDA elevates whereas the SOD production decreases on administering the KA at various time intervals. Sita shows protective action against the KA-induced SE by reducing the oxidative stress thus inhibiting the change in SOD and MDA was observed after KA administration prior SE onset. Based on the above results, the study explains possible molecular mechanism of Sita. Sita Pretreatment showed significant elevation in expression of Nrf2 and HO-1 proteins in hippocampus region of the brain.
Above parameters defines the potential effect of Sita on brain injury occurred due to SE by anti-oxidative pathway.
西他列汀（Sita）是一种二肽基肽酶-4 抑制剂，已被批准用于治疗 2 型糖尿病（T2D），并已报道其具有神经保护和抗氧化活性。本文描述了 Sita 对红藻氨酸（KA）诱导的 SE 大鼠模型的治疗作用，并研究了 Sita 的抗氧化途径。
雄性 Sprague-Dawley 大鼠随机分为四组： vehicle control、KA 和 Sita+KA（分别以 5 和 10mg/kg 剂量进一步分组）。通过腹腔内（IP）给予磷酸盐缓冲盐水（PBS）中的 KA（15mg/kg）诱导大鼠 SE。评估 SE 强度、氧化应激参数、TUNEL 测定、组织病理学和 Nrf2/HO-1 表达。
与诱导组（KA）相比，Sita 预处理大鼠 SE 的潜伏期延长，从而延迟了疾病的开始，SE 的发生率降低。在不同时间间隔给予 KA 后，MDA 的含量增加，而 SOD 的产生减少。Sita 通过减少氧化应激对 KA 诱导的 SE 表现出保护作用，从而抑制了 SOD 和 MDA 的变化，这在 SE 发作前给予 KA 后得到观察。基于上述结果，研究解释了 Sita 的可能分子机制。Sita 预处理显著提高了大脑海马区 Nrf2 和 HO-1 蛋白的表达。
上述参数定义了 Sita 通过抗氧化途径对 SE 引起的脑损伤的潜在影响。
