| Background:Stroke is a disease of serious harm to people’s health,it is the first leading cause of disability in our country and the second leading cause of death, to individuals.families and society bring heavy blow and burden.The incidence of ischemic stroke accounted for 60%～80%,and has long been a lack of effective treatments. At present how to effectively reduce the damage and promote the rehabilitation of brain stroke patients is important hot topic in the field of neuroscience. Cerebral ischemia can activate the surrounding tissue regeneration response, including nerve regeneration and angiogenesis. Angiogenesis is based on the original blood vessels by vascular endothelial cell proliferation, migration, buds, blood vessels division, branch to form a new capillary network biological processes. After brain injury angiogenesis plays an important role in the process of repair, not only is helpful to supply oxygen and nutrients in affected regions, and promote neurogenesis and synaptic plasticity, is beneficial to the recovery of neural function. Clinical autopsy results confirmed that the number of new blood vessels around after ischemic infarcts and stroke survival rates, time, and the neural functional recovery were positively correlated.Angiogenesis is ischemic tissue damage and nerve repair structure foundation, but compensatory angiogenesis after ischemic stroke often lack of compensatory. The mechanism of angiogenesis after cerebral ischemia remain unclear. Further clarify the molecular mechanism of angiogenesis after cerebral ischemia is the foundation of the development of therapeutic angiogenesis, and therapeutic angiogenesis will be promoting a new method of nervous function recovery. Caveolae is formed by the cytoplasm membrane inward concave of a specialized cystic structure of cytoplasm membrane, abundants in fat cells, endothelial cells, type I alveolar cells, fibroblasts, smooth muscle cells and striated muscle cells. Caveolae is mainly composed of lipid and protein, the cytoplasmic surface covered with a layer of membrane coat, the coat is the main component of Caveolin family, the family has three members, respectively is Caveolin-1, Caveolin-2and Caveolin-3. It is generally believed that Caveolin-1 plays a main role in the biological function. Caveolin-1 (Cav-1) is the main structural protein of Caveolae, is the symbol of the constitute Caveolae, while plays a role in maintaining the integrity of Caveolae, cholesterol transport, vesicular transport, Signal transduction. Cav-1 is rich in various types of cells, endothelial cells and smooth muscle cells are content is one of the most abundant cell type. The structure and function of Cav-1 from worms to human have a high degree of similarity, show that Cav-1 is very important to maintain cell function. The endothelial cells of vascular endothelial cell growth factor (VEGF) expression of physiological activity needs Cavl participation and regulation. In recent years, the study found, Cav-1 involved in tumor growth, angiogenesis and so on the various physiological and pathological process, is the key factor of angiogenesis, but whether Cav-1 participated in the adult animals of angiogenesis after cerebral ischemia has not been reported. This study examined the expression of Cav-1 change after cerebral ischemia, adopted the lentivirus transfection Cav-1 siRNA inhibit the expression of Cav-1 and explored Cav-1 role in angiogenesis after cerebral ischemiaObjective:To investigate the expression and the involvement of Caveolin-1 (Cav-1) in postischemic angiogenesis using a rat model of ischemic stroke.Methods:Normal male Wistar rats were randomly divided into 4 groups:the Sham group (Sham group, n=15) the cerebral ischemia group (MCAO group, n=55), lentivirus-expressing Cav-1 siRNA treated group (siRNA group, n=20) and lentivirus-expressing nonsense siRNA treated group (misRNA group, n=20). Q-PCR and western blot analysis were used to detect the expression of Cav-1. FITC-dextran was used to detect the vessel volume, and Laser Doppler was used to measure the local cerebral blood flow in ischemic penumbral.Results:The expressions of Cav-1 from hour 4 to day 3 post-MCAO significantly decreased in MCAO group, compared with sham group (all P<0.05), and the minimum level appeared at day 3 post-MCAO (P<0.01). Interestingly, the expression of Cav-1 on day 7 post-MCAO was significantly restored (P<0.05), and restored to normal level on day 14 post-MCAO (P>0.05). As expected, in Cav-1 siRNA group, the expression of Cav-1 significantly decreased compared with MCAO or misRNA group (all P<0.05). Meanwhile, there were significantly weakened vessel volume and local cerebral blood flow in ischemic penumbral (P<0.05).Conclusion:Cav-1 might be involved in postischemic angiogenesis. Further investigation of the regulation molecular machenism of Cav-1 in postischemic angiogenesis may be helpful for therapeutic angiogenesis for ischemic stroke. |
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