动物造模 z-bio 2021-07-14 396

　　Objective: 17-β-estradiol (E2) replacement therapy to study the pathological changes of the cerebral microvascular system after permanent ligation of bilateral common carotid arteries (BCCAO) in rats and the effect of E2 replacement at different times. The treatment of chronic hypotension may be induced by perfusion The mechanism that plays a role in the occurrence and development of vascular dementia.

　　Method: Experimental animals were randomly divided into initial BCCAO: sham (3d), BCCAO 3d group, BCCAO 3d+E2 group, advanced BCCAO: sham (3 months), BCCAO 3 months, BCCAO 3 months. In the E2 group. Immunohistochemistry was used to detect IgG leakage in each group, the ultra-fine structure of blood vessels in each group was observed under electron microscope, and the expression of vascular endothelial growth factor (VEGF) was detected by Western blot.

　　Results: The results of immunohistochemistry showed that compared with the corresponding sham (3d or 3m) group, a large number of damaged blood vessels in the cortex and hippocampus CA1 area of the 3d and 3m groups after BCCAO were surrounded by IgG. Immunostaining showed that the perivascular hippocampal CA1 area staining in IgG BCCAO3m group was weaker than that in BCCAO3d group; continuous administration of E2 significantly reduced vascular IgG leakage. Electron microscopy results showed that the perivascular edema in the hippocampal CA1 area of the BCCAO3d group and March group was severe, the blood vessels were slightly dilated, and the ultrafine structure of endothelial cells was damaged. The administration of E2 can significantly enhance the ultrafine structure of blood vessels, which can be improved. Western blot results showed that VEGF expression in hippocampal CA1 area increased significantly at 6 hours and 1 day after BCCAO, and then decreased significantly, reaching the lowest level after 3 days. The BCCAO at 3 months was significantly lower than the VEGF level of the sham (March) group. 3 days after the expression of BCCAO or VEGF in hippocampal CA1 area, E2 can be significantly increased.

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