Department of Anesthesiology, Changhai hospital, Naval Medical University, Changhai Road NO.168, Shanghai City, 200433, People's Republic of China.
BMC Neurol. 2019 Nov 15;19(1):289. doi: 10.1186/s12883-019-1508-y.
Ischemia-reperfusion (I/R)-induced vascular dysfunction is the main factor to acute ischemic stroke. Sirt3 is one of the sirtuin family members, which plays an important role in the development of neurological diseases.
In this study, we constructed I/R injury model on HBMEC cells and induced the overexpression of Sirt3 in model cells. Meanwhile, the p38 activator U-46619 was used to examine the connection between Sirt3 and p38. We also examined the level of endothelial associated proteins, including occluding, ZO-1 and claudin-4 by using qRT-PCR and western blot.
Our findings indicated that overexpression of Sirt3 decreased the permeability of model cells and promoted in the growth of endothelial cells. However, the activation of p38 could antagonize the function of Sirt3 in HBMEC cells. Moreover, Our results indicated a positive correlation between Sirt3 and inter-endothelial junction proteins. Importantly, PPAR-γ agonist and inhibitor were utilized to investigate the role of PPAR-γ in Sirt3 mediated cell function. Sirt3 was targeted by PPAR-γ in model cells.
Taken together, this research not only demonstrated PPAR-γ might benefit to the growth of endothelial cell though activating Sirt3 but also indicated its potential value in the treatment for ischemic stroke.
缺血再灌注（I/R）引起的血管功能障碍是急性缺血性脑卒中的主要因素。Sirt3 是沉默调节蛋白家族的成员之一，在神经退行性疾病的发展中发挥着重要作用。
在这项研究中，我们构建了 HBMEC 细胞的 I/R 损伤模型，并在模型细胞中诱导 Sirt3 的过表达。同时，使用 p38 激活剂 U-46619 来检验 Sirt3 和 p38 之间的联系。我们还通过 qRT-PCR 和 Western blot 检测内皮相关蛋白（包括 occluding、ZO-1 和 claudin-4）的水平。
我们的研究结果表明，Sirt3 的过表达降低了模型细胞的通透性，并促进了内皮细胞的生长。然而，p38 的激活可以拮抗 Sirt3 在 HBMEC 细胞中的功能。此外，我们的研究结果表明 Sirt3 与内皮细胞间连接蛋白之间存在正相关。重要的是，我们使用过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂和抑制剂来研究 PPAR-γ 在 Sirt3 介导的细胞功能中的作用。Sirt3 是模型细胞中 PPAR-γ 的靶点。
综上所述，本研究不仅表明 PPAR-γ 通过激活 Sirt3 可能有益于内皮细胞的生长，而且还表明其在缺血性脑卒中治疗中的潜在价值。
