Department of Neurology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
Department of Neurology, Hebei General Hospital, No. 348 Heping West Road, Xinhua District, Shijiazhuang, 050051, Hebei, China.
J Mol Neurosci. 2021 Apr;71(4):767-777. doi: 10.1007/s12031-020-01697-3. Epub 2020 Sep 10.
Ischemic stroke is the primary cause of disability and mortality worldwide. Ischemia/reperfusion (I/R)-induced microcirculatory dysfunction and organ injury generally occur after ischemic stroke. Several studies have shown that intermedin (IMD) has a regulating function on cerebral microcirculation and blood-brain barrier via relaxing cerebral vessels and improving the local blood supply after cerebral ischemia. However, a unified conclusion has not been reached, and the underlying mechanism remains unclear. To observe and analyze the changes of cerebral microcirculation perfusion of cerebral IRI by IMD post-treatment in the rats and further explore the mechanism underlying the beneficial effect of IMD on cerebral IRI. Thirty-nine rats were divided into three groups: sham, I/R, and I/R + IMD groups. After IMD ischemia post-treatment, the rat cerebral infarction rate and the degree of neurological deficit were evaluated by TTC staining and neurological function score; the changes in the amount of cerebral microcirculation implantation on the injured side of the rats were observed by laser Doppler; the pathological changes and cell ultrastructure of rat cortex and hippocampus were observed by HE staining and transmission electron microscopy; the neuron apoptosis in the rat cortex and hippocampus was detected by TUNEL staining and immunohistochemical staining. Impaired neurological function, abnormal cortical/hippocampal neuron morphology, and the proportion of cerebral infarction were significantly improved in the IMD group compared with the I/R group, which suggested a possible neuroprotective role of IMD. IMD treatment also increased the average perfusion of cerebral surface microcirculation in rats by astonished 42.7 times. Finally, IMD administration decreased the caspase-3- and Bax-positive cell numbers and apoptotic cell ratio. IMD has a significant protective effect on neuronal damage caused by cerebral I/R in rats by improving cerebral microcirculation and inhibiting apoptosis.
缺血性脑卒中是全球范围内导致残疾和死亡的主要原因。缺血/再灌注（I/R）引起的微循环功能障碍和器官损伤通常发生在缺血性脑卒中之后。几项研究表明，中介素（IMD）通过舒张脑血管和改善脑缺血后的局部血液供应，对脑微循环和血脑屏障具有调节作用。然而，尚未得出统一的结论，其潜在机制仍不清楚。观察和分析 IMD 后处理对脑 IRI 大鼠脑微循环灌注的变化，并进一步探讨 IMD 对脑 IRI 有益作用的潜在机制。39 只大鼠分为三组：假手术组、IRI 组和 I/R+IMD 组。在 IMD 缺血后处理后，通过 TTC 染色和神经功能评分评估大鼠脑梗死率和神经功能缺损程度；通过激光多普勒观察大鼠损伤侧脑微循环植入量的变化；通过 HE 染色和透射电镜观察大鼠皮质和海马的病理变化和细胞超微结构；通过 TUNEL 染色和免疫组化染色检测大鼠皮质和海马神经元凋亡。与 I/R 组相比，IMD 组大鼠神经功能损伤、皮质/海马神经元形态异常和脑梗死比例明显改善，提示 IMD 可能具有神经保护作用。IMD 治疗还使大鼠脑表面微循环的平均灌注增加了惊人的 42.7 倍。最后，IMD 给药减少了 caspase-3 和 Bax 阳性细胞数量和凋亡细胞比例。IMD 通过改善脑微循环和抑制细胞凋亡，对大鼠脑 I/R 引起的神经元损伤具有显著的保护作用。
