基于脑小血管病临床脑血流特点构建并评估 不完全性全脑缺血再灌注大鼠模型

AIM: To construct and evaluate an incomplete global cerebral ischemia-reperfusion rat model based on the hemodynamic characteristics of cerebral small vessel disease （CSVD）, so as to provide an ideal rat model for investigating ischemic cerebrovascular diseases such as CSVD. METHODS: A total of 126 male SD rats were divided into sham, minor, and serious groups （n=42）. The bilateral common carotid artery clamp-open circulation operation was used to construct the incomplete global cerebral ischemia-reperfusion rat model, and real-time changes of cerebral hemodynamics were assessed by a laser speckle blood flow imaging system. At 2, 24 and 72 h after the model was constructed, the survival rate and animal behavior （beam balance test, BBT） score were evaluated, and the materials of the model animals were taken. HE staining was used to observe the histopathological changes in different brain regions of the rats, and non-targeted metabonomics was utilized to analyze the different metabolites in the rat plasma and cerebral cortex, thus evaluating the damage degree. RESULTS: The average survival rates of rats in minor and serious groups were 83. 2% and 73. 7% （P<0. 05）, and the mean residual cerebral blood flow rates were 56. 3% and 40. 9%, respectively. The BBT scores at 2, 24 and 72 h after modeling in minor and serious groups were higher than those in sham group （P<0. 05）. The HE staining results showed that the neurons in the extensive cerebral cortex （especially in M1 and RSA）, ventrolateral part of ventromedial hypothalamus （VMHvl） and hippocampal C2 region showed morphological changes at different degrees. The non-targeted metabonomics analysis revealed a total of 45 differential metabolites in the plasma of sham and serious groups, comprising 33 up-regulated and 12 down-regulated metabolites. In addition, the RSA exhibited 19 differential metabolites, including 6 up-regulated and 13 down-regulated metabolites. This finding suggests that the modeling disrupted neuroendocrine function in the rats. CONCLUSION: The bilateral common carotid artery occlusion and open circulation model can lead to diffuse and extensive damage to the cerebral cortex, VMHvl, and hippocampal C2 region in rats, and the injury mechanism may be linked to metabolic disorders, oxidative stress damage, and other factors. This model provides a new experimental model for investigating repeated ischemia-reperfusion injury in rats with CSVD. [ABSTRACT FROM AUTHOR]