Departments of Neurology, Departments of Endocrinology, Departments of Physical Examination, Personnel Section; People's Hospital of Zouping County of Shandong Province, China.
Eur Rev Med Pharmacol Sci. 2018 May;22(10):3166-3172. doi: 10.26355/eurrev_201805_15077.
The collateral circulation development is considered as a compensatory inherent mechanism to restore damaged blood perfusion after ischemia. We aimed to detect the collateral flow and the mean blood-flow velocities (mBFVs) level in the basilar trunk during or after cerebral hypoxia-ischemia in the mice brain and explore the effect of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow.
C57BL/6J mice and the nNOS knockout (KO) mice were randomly divided into a sham-operated group (control) and the hypoxia-ischemia (HI) groups that were treated with the phosphate buffered solution (PBS) control or 7-nitroindazole (7-NI). Cortexes were harvested after the HI treatment for analysis of nNOS expression using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Ultrasound imaging experiments were performed to detect the collateral flow and the mBFVs level in the basilar trunk.
After cerebral HI, the cortical nNOS mRNA and protein levels increased markedly compared with the sham-operated control mice. Besides, 7-NI treatment had no effect on the blood flow in the sham-operated control mice. What's more, either the 7-NI pretreatment or the nNOS gene knockdown before the HI procedure could attenuate the brain injury by the increased collateral flow and the decreased mBFVs level in the basilar trunk.
nNOS inhibition protected hypoxic-ischemic-induced mice brain damage by the increased collateral flow and the decreased mBFVs level in the basilar trunk. Therefore, the 7-NI administration may have potential utility for the treatment of HI injury in human beings.
侧支循环的发展被认为是一种内在的代偿机制，可在缺血后恢复受损的血液灌注。我们旨在检测小鼠脑缺氧缺血过程中或之后基底干的侧支血流和平均血流速度（mBFVs）水平，并探讨神经元型一氧化氮合酶（nNOS）抑制对侧支血流的影响。
C57BL/6J 小鼠和 nNOS 基因敲除（KO）小鼠随机分为假手术组（对照组）和缺氧缺血（HI）组，HI 组用磷酸盐缓冲液（PBS）对照或 7-硝基吲唑（7-NI）处理。HI 处理后采集皮质，采用 Western blot 和逆转录聚合酶链反应（RT-PCR）分析 nNOS 表达。超声成像实验检测基底干侧支血流和 mBFVs 水平。
与假手术对照组相比，脑 HI 后皮质 nNOS mRNA 和蛋白水平明显增加。此外，7-NI 处理对假手术对照组的血流无影响。更重要的是，7-NI 预处理或 HI 前 nNOS 基因敲低均可通过增加侧支血流和降低基底干 mBFVs 水平减轻脑损伤。
nNOS 抑制通过增加侧支血流和降低基底干 mBFVs 水平来保护缺氧缺血诱导的小鼠脑损伤。因此，7-NI 给药可能对人类 HI 损伤的治疗具有潜在的应用价值。
