Department of Anesthesiology, Department of Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, No270 DongAn Road, 200032, Shanghai, People's Republic of China.
Department of Gynecologic Oncology, Department of Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Fudan University, No270 DongAn Road, 200032, Shanghai, People's Republic of China.
J Anesth. 2018 Dec;32(6):856-865. doi: 10.1007/s00540-018-2565-x. Epub 2018 Oct 6.
Angiotensin II (Ang II) has been shown to be involved in neurological disorders. Propofol demonstrated neuroprotective effects in neurons.
Mouse hippocampal HT22 cells were pre-treated with propofol, followed by Ang II treatment. The expression of synaptic proteins (synapsin I and PSD95) was examined. The effects of propofol on Ang II-induced NADPH oxidase expression and superoxide anion generation were examined. The effects of propofol on intracellular calcium concentration, the activation of calcium/calmodulin-dependent protein kinase II (CaMKII), and protein kinase C (PKC) were measured.
Ang II reduced the expression of synapsin I and PSD95, which was attenuated by propofol. Ang II-induced effects were blocked by Ang II type 1 receptor (AT1 receptor) blocker. Ang II induced the expression of NADPH oxidase and caused superoxide anion accumulation, which were attenuated by propofol. In addition, propofol induced intracellular calcium concentration, and activated CaMKII as well as PKCβ. Importantly, the Ang II-mediated effects were diminished by α-tocopherol, and the propofol-mediated effects were alleviated by calcium chelator, CaMKII inhibitor, and PKCβ inhibitor.
Ang II, via AT1 receptor, induced oxidative stress and reduced the expression of synapsin I and PSD95 in HT22 cells. Propofol may increase synapsin I and PSD95 expression by inhibiting oxidative stress and stimulating calcium signaling pathway.
血管紧张素 II（Ang II）已被证明参与神经紊乱。丙泊酚在神经元中表现出神经保护作用。
用丙泊酚预处理 HT22 细胞，然后用 Ang II 处理。检测突触蛋白（突触素 I 和 PSD95）的表达。检测丙泊酚对 Ang II 诱导的 NADPH 氧化酶表达和超氧阴离子生成的影响。测量丙泊酚对细胞内钙离子浓度、钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）和蛋白激酶 C（PKC）的激活作用。
Ang II 降低了突触素 I 和 PSD95 的表达，丙泊酚减弱了这一作用。Ang II 型 1 受体（AT1 受体）阻滞剂阻断了 Ang II 的作用。Ang II 诱导 NADPH 氧化酶的表达并导致超氧阴离子的积累，丙泊酚减弱了这一作用。此外，丙泊酚诱导细胞内钙离子浓度升高，并激活 CaMKII 和 PKCβ。重要的是，α-生育酚减弱了 Ang II 介导的作用，钙螯合剂、CaMKII 抑制剂和 PKCβ 抑制剂减轻了丙泊酚介导的作用。
Ang II 通过 AT1 受体诱导氧化应激，降低 HT22 细胞中突触素 I 和 PSD95 的表达。丙泊酚可能通过抑制氧化应激和刺激钙信号通路来增加突触素 I 和 PSD95 的表达。
