Zhai Li, Liu Min, Wang Tingting, Zhang Hongyan, Li Shan, Guo Yunliang
Department of Pharmacy, The Third Clinical Medical College of Qingdao University, Qingdao, Shandong Province, China.
Institute of Cerebrovascular Disease, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
PLoS One. 2017 Apr 7;12(4):e0174414. doi: 10.1371/journal.pone.0174414. eCollection 2017.
Thrombolysis is used to improve cerebral circulation; at the same time, neuroprotective drugs such as antioxidants should also be used. The aim of these experiments was to explore the protective mechanism of an antioxidant, picroside II, on the blood-brain barrier (BBB) after cerebral ischemia-reperfusion (CI/R) injury.
To observe the antagonistic effect of picroside II on CI/R damage, the neurological deficit score and the infarct volume were measured. To detect the protective effect of picroside II on nerve cells and the BBB, the morphology and structure of cortical brain tissue were observed, respectively. To investigate the antioxidant effect and mechanism of picroside II, reactive oxygen species (ROS) content, the activity of Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and the protein levels of Nox2 and Rac-1 were detected. To investigate the protective mechanism of picroside II on the BBB, the levels of ROCK, MLCK, MMP-2 and claudin-5 were tested.
A higher neurological score, bigger cortex infarction, more damaged neuron structure and injured BBB, increased content of ROS and activity of NADPH oxidase, higher protein levels of Nox2, Rac-1, ROCK, MLCK and MMP-2 and lower levels of claudin-5 were observed in the model group. In the picroside group, the neurological score, neuronal damage, BBB injury, ROS content and NADPH oxidase activity were reduced (P<0.05), and the protein levels of Rac-1, Nox2, ROCK, MLCK and MMP-2 were down-regulated (P<0.05), while the expression of claudin-5 was up-regulated (P<0.05).
Picroside II could protect the nervous system possibly through reducing the content of ROS by down-regulating the expression of Rac-1 and Nox2 and could protect the BBB through reducing the expression of ROCK, MLCK, and MMP-2, while enhancing the expression of claudin-5.
溶栓治疗用于改善脑循环；与此同时，还应使用抗氧化剂等神经保护药物。这些实验的目的是探讨抗氧化剂胡黄连苷II对脑缺血再灌注（CI/R）损伤后血脑屏障（BBB）的保护机制。
为观察胡黄连苷II对CI/R损伤的拮抗作用，测量神经功能缺损评分和梗死体积。为检测胡黄连苷II对神经细胞和血脑屏障的保护作用，分别观察皮质脑组织的形态和结构。为研究胡黄连苷II的抗氧化作用及机制，检测活性氧（ROS）含量、烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶）活性以及Nox2和Rac-1的蛋白水平。为研究胡黄连苷II对血脑屏障的保护机制，检测ROCK、MLCK、MMP-2和claudin-5的水平。
模型组观察到神经功能评分更高、皮质梗死面积更大、神经元结构损伤更严重、血脑屏障受损、ROS含量增加、NADPH氧化酶活性升高、Nox2、Rac-1、ROCK、MLCK和MMP-2的蛋白水平更高以及claudin-5水平更低。在胡黄连苷组，神经功能评分、神经元损伤、血脑屏障损伤、ROS含量和NADPH氧化酶活性降低（P<0.05），Rac-1、Nox2、ROCK、MLCK和MMP-2的蛋白水平下调（P<0.05），而claudin-5的表达上调（P<0.05）。
胡黄连苷II可能通过下调Rac-1和Nox2的表达降低ROS含量来保护神经系统，并通过降低ROCK、MLCK和MMP-2的表达，同时增强claudin-5的表达来保护血脑屏障。
