Mastantuono Teresa, Di Maro Martina, Chiurazzi Martina, Battiloro Laura, Muscariello Espedita, Nasti Gilda, Starita Noemy, Colantuoni Antonio, Lapi Dominga
Department of Clinical Medicine and Surgery, "Federico II" University Medical School, Naples, Italy.
Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS - "Fond. G. Pascale", Naples, Italy.
Front Physiol. 2018 May 15;9:540. doi: 10.3389/fphys.2018.00540. eCollection 2018.
The reactive oxygen species (ROS) are known to play a major role in many pathophysiological conditions, such as ischemia and reperfusion injury. The present study was aimed to evaluate the cyanidin (anthocyanin) effects on damages induced by rat pial microvascular hypoperfusion-reperfusion injury by cerebral blood flow decrease (CBFD) and subsequent cerebral blood flow recovery (CBFR). In particular, the main purpose was to detect changes in ROS production after cyanidin administration. Rat pial microvasculature was investigated using fluorescence microscopy through a cranial window (closed); Strahler's method was utilized to define the geometric features of pial vessels. ROS production was investigated by 2'-7'-dichlorofluorescein-diacetate assay and neuronal damage was measured on isolated brain sections by 2,3,5-triphenyltetrazolium chloride staining. After 30 min of CBFD, induced by bilateral common carotid artery occlusion, and 60 min of CBFR, rats showed decrease of arteriolar diameter and capillary perfusion; furthermore, increase in microvascular leakage and leukocyte adhesion was observed. Conversely, cyanidin administration induced dose-related arteriolar dilation, reduction in microvascular permeability as well as leukocyte adhesion when compared to animals subjected to restriction of cerebral blood flow; moreover, capillary perfusion was protected. ROS generation increase and marked neuronal damage were detected in animals subjected to CBFD and CBFR. On the other hand, cyanidin was able to reduce ROS generation and neuronal damage. In conclusion, cyanidin treatment showed dose-related protective effects on rat pial microcirculation during CBFD and subsequent CBFR, inducing arteriolar dilation by nitric oxide release and inhibiting ROS formation, consequently preserving the blood brain barrier integrity.
已知活性氧（ROS）在许多病理生理状况中起主要作用，如缺血和再灌注损伤。本研究旨在评估矢车菊素（花青素）对大鼠软脑膜微血管因脑血流量减少（CBFD）及随后的脑血流量恢复（CBFR）所诱导的灌注 - 再灌注损伤的影响。特别地，主要目的是检测矢车菊素给药后ROS产生的变化。通过颅骨视窗（封闭）利用荧光显微镜对大鼠软脑膜微血管进行研究；采用斯特拉勒方法确定软脑膜血管的几何特征。通过2′,7′ - 二氯荧光素二乙酸酯测定法研究ROS产生情况，并通过2,3,5 - 三苯基氯化四氮唑染色在离体脑切片上测量神经元损伤。在双侧颈总动脉闭塞诱导30分钟CBFD及60分钟CBFR后，大鼠出现小动脉直径减小和毛细血管灌注减少；此外，观察到微血管渗漏和白细胞黏附增加。相反，与脑血流量受限的动物相比，矢车菊素给药诱导剂量相关的小动脉扩张、微血管通透性降低以及白细胞黏附减少；而且，毛细血管灌注得到保护。在经历CBFD和CBFR的动物中检测到ROS生成增加和明显的神经元损伤。另一方面，矢车菊素能够减少ROS生成和神经元损伤。总之，矢车菊素治疗在CBFD及随后的CBFR期间对大鼠软脑膜微循环显示出剂量相关的保护作用，通过一氧化氮释放诱导小动脉扩张并抑制ROS形成，从而保持血脑屏障的完整性。
