Department of Neurology, The First People's Hospital of Jiande, Jiande, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(15):6665-6671. doi: 10.26355/eurrev_201908_18557.
To investigate the influences of urinary kallidinogenase on neuronal apoptosis in rats with cerebral infarction through the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) oxidative stress pathway.
A total of 30 male rats were divided into group A (model control group), group B (rat model of cerebral infarction) and group C (rat model of cerebral infarction + medical treatment with urinary kallidinogenase). The percentage of cerebral infarct volume and the apoptosis of brain cells in the three groups of rats were detected via 2,3,5-Triphenyltetrazolium chloride (TTC) staining, the pathological morphology of brain tissues in the three groups of rats was observed via hematoxylin and eosin (HE) staining, and the protein levels of Nrf2 and superoxide dismutase 1 (SOD1) in the brain tissues in the three groups of rats were measured using the Western blotting assay.
The degree of neurological deficit in group B was remarkably higher than that in group A (p<0.05), and it was markedly decreased in group C compared to that in group B, displaying statistically significant differences (p<0.05). Compared to that in group A, the cell apoptosis was significantly aggravated in group B, while a remarkably alleviated cell apoptosis was observed in group C compared to that of group B, and the differences were statistically significant (p<0.05). The cerebral infarct volume accounted for 34.87% of the whole brain volume in group B, and a mild cerebral infarction was detected in group C, with a percentage of cerebral infarct volume of 21.14%. Group B showed a more evident increase in the cerebral infarct volume than in group C (p<0.05). Compared to those of group A, pyknotic nuclei and neuron staining of brain tissue cells were evidently increased, and the neuronal cell injury was aggravated in group B. Moreover, prominently decreased pyknotic nuclei and neuron staining (p<0.05) as well as mild neuronal cell injury (p<0.05) were detected in group C compared to those in group B. The levels of Nrf2 and SOD1 protein in the brain tissues in group B were remarkably lower than those of group C (p<0.05).
Urinary kallidinogenase can inhibit the neuronal apoptosis in rats and protect the rats from cerebral infarction, whose mechanism is associated with the activation of the Nrf2/ARE oxidative stress pathway.
通过核因子红细胞 2 相关因子 2（Nrf2）/抗氧化反应元件（ARE）氧化应激通路研究尿激肽原酶对脑梗死大鼠神经元凋亡的影响。
将 30 只雄性大鼠分为 A 组（模型对照组）、B 组（脑梗死大鼠模型）和 C 组（脑梗死大鼠+尿激肽原酶治疗）。采用 2,3,5-三苯基氯化四氮唑（TTC）染色法检测三组大鼠脑梗死体积百分比和脑细胞凋亡情况，HE 染色法观察三组大鼠脑组织病理形态，Western blot 法检测三组大鼠脑组织 Nrf2 和超氧化物歧化酶 1（SOD1）蛋白水平。
B 组大鼠神经功能缺损程度明显高于 A 组（p<0.05），C 组明显低于 B 组，差异有统计学意义（p<0.05）。与 A 组比较，B 组细胞凋亡明显加重，C 组细胞凋亡明显减轻，差异有统计学意义（p<0.05）。B 组大脑梗死体积占全脑体积的 34.87%，C 组为轻度脑梗死，占 21.14%。B 组脑梗死体积明显大于 C 组（p<0.05）。与 A 组比较，B 组脑组织细胞出现明显的核固缩和神经元染色，神经细胞损伤加重；C 组核固缩和神经元染色明显减少（p<0.05），神经细胞损伤减轻（p<0.05）。与 A 组比较，B 组脑组织 Nrf2 和 SOD1 蛋白水平明显降低（p<0.05）。
尿激肽原酶可抑制脑梗死大鼠神经元凋亡，减轻脑损伤，其机制与激活 Nrf2/ARE 氧化应激通路有关。
