动物造模 z-bio 2022-02-28 333

　　Objective: By detecting the pathological changes of cerebral microvessels in different periods after permanent ligation of bilateral common carotid arteries (BCCAO) in rats and the effect of physiological dose of 17-β-estradiol (E2) replacement therapy, to explore the effect of E2 replacement therapy on chronic hypoglycemia. The role and possible mechanism in the development of perfusion-induced vascular dementia.

　　Methods: Experimental animals were randomly divided into early BCCAO: sham (3 d), BCCAO 3 d group, BCCAO 3 d+E2 group; late post-BCCAO: sham (3 months), BCCAO 3 months and BCCAO 3 months and continued to give E2 group . The leakage of IgG in each group was detected by immunohistochemistry, the ultrastructure of blood vessels in each group was observed by electron microscope, and the expression of vascular endothelial growth factor (VEGF) was detected by Western blot.

　　RESULTS: Immunohistochemical results showed that compared with the corresponding sham (3 d or 3 m) group, a large number of damaged blood vessels in the cortex and hippocampal CA1 area of the 3 d and 3 m groups after BCCAO were surrounded by IgG immunostaining; Compared with the group, the staining of IgG around the blood vessels in the BCCAO 3 m group in the hippocampal CA1 region was weaker; continuous administration of E2 could significantly reduce the leakage of vascular IgG. Electron microscope results showed that the perivascular edema in the hippocampal CA1 region of the BCCAO 3 d and 3 months group was severely edema, the blood vessels were slightly dilated and the ultrastructure of endothelial cells was damaged; E2 administration could significantly improve the ultrastructure of blood vessels. Western blot results showed that the expression of VEGF in hippocampal CA1 region increased significantly at 6 h and 1 d after BCCAO, then decreased significantly, and reached the lowest level at 3 d; VEGF level in BCCAO at 3 months was significantly lower than that in sham (3 months) group; E2 significantly decreased The expression of VEGF in hippocampal CA1 region was increased 3 days or 3 months after BCCAO.

　　Conclusion: BCCAO can lead to vascular structural damage in the early stage, and this damage can last until 3 months after BCCAO. Physiological dose of E2 replacement therapy may reduce BCCAO-induced vascular dementia by up-regulating the protein expression of VEGF.