毛钩藤碱在脑缺血再灌注损伤动物模型中的保护作用

Protective effect of Hirsutine on animal models of cerebral ischemia-reperfusion injury

目的探究毛钩藤碱(Hirsutine)在大鼠脑缺血再灌注损伤(CIRI)中的神经保护作用及其潜在机制。方法SD大鼠用于建立大脑中动脉闭塞再灌注(MCAO/R)模型,并将大鼠分为6个实验组(n=6):对照组;模型组;Hirsutine低剂量(5 mg/kg)组;Hirsutine中剂量(10 mg/kg)组;Hirsutine高剂量(20 mg/kg)组;依达拉奉(30 mg/kg,阳性对照)组。取脑组织进行TTC染色,测量脑梗死和神经行为缺陷;HE和Nissl染色检测神经元损伤;Tunel染色检测海马细胞凋亡;ELISA法检测脑组织活性氧(ROS),丙二醛(MDA),超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平;蛋白质印迹检测机制相关蛋白的表达水平。结果Hirsutine治疗显著减轻了MCAO/R大鼠的脑梗死和神经元损伤,并改善了脑神经行为缺陷。Hirsutine有效抑制氧化应激和细胞凋亡。此外,Hirsutine激活了MCAO/R大鼠神经元中的PI3K/Akt/Nrf2通路。结论Hirsutine通过激活PI3K/Akt/Nrf2信号通路改善MCAO/R大鼠脑组织氧化应激和细胞凋亡,从而缓解CIRI诱导的神经元损伤。

Objective To explore the neuroprotective effect and potential mechanism of Hirsutine in rat cerebral ischemia-reperfusion injury(CIRI).Methods SD rats were used to establish a middle cerebral artery occlusion reperfusion(MCAO/R)model and were divided into 6 groups(n=6):Control group;Model group;Hirsutine low-dose(5 mg/kg)group;Hirsutine medium dose(10 mg/kg)group;Hirsutine high-dose(20 mg/kg)group;Edaravone(30 mg/kg,positive control)group.TTC staining was performed on brain tissue,the cerebral infarction and neurobehavioral defects were measured.HE and Nissl staining were used to detect neuronal damage.Tunel staining was used to detect hippocampal cell apoptosis;ELISA method was used to detect the levels of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH Px)in brain tissues.Western blotting is used to detect the expression level of proteins related to the mechanism.Results The results showed that Hirsutine treatment significantly reduced cerebral infarction and neuronal damage in MCAO/R rats,and improved brain neurobehavioral deficits.Hirsutine effectively inhibited oxidative stress and cell apoptosis.In addition,Hirsutine activated the PI3K/Akt/Nrf2 pathway in MCAO/R rat neurons.Conclusion Hirsutine improveed oxidative stress and apoptosis in MCAO/R rat brain by activating PI3K/Akt/Nrf2 signaling pathway,thereby alleviating CIRI-induced neuronal injury.