Dynamic changes of Apo A1 mediated by LXR/RXR/ABCA1 pathway in brains of the aging rats with cerebral hypoperfusion

摘要

Cerebral hypoperfusion or aging often results into the disturbances of cholesterol and lipoprotein, which have been tightly associated with numerous neurological and psychiatric diseases, such as vascular dementia. The pathway of liver X receptor-β (LXR-β)/retinoic X receptor-α (RXR-α)/ABCA1 plays a vital role in lipoprotein metabolism. However, there were no reports about the relationship between the signal molecules of the pathway and lipoprotein homeostasis in cerebral hypoperfusion models. Therefore, we aimed to detect the expression of the pathway molecules in the aging rat models of chronic cerebral hypoperfusion and to explore its underlying mechanism. The model with cerebral hypoperfusion was established by ligating of the bilateral common carotid arteries (2VO). The temporal blood flow in the model rats was significantly decreased 14 d, 21 d and 28 d after 2VO compared with the control. The serum levels of high-density lipoprotein (HDL) and total cholesterol (TC) were reached a peak at 14 d, then, they were gradually decreased. The changes of LXR-β, RXR-α, ABCA1 and apolipoprotein A1 (apo A1) of the pathway were consistent with the changes of HDL and TC. We conclude that LXR-β/RXR-α/ABCA1 and downstream genes apo A1 undergo dynamic changes during the process of cerebral hypoperfusion. The LXR-β/RXR-α/ABCA1 mediated apo A1 cholesterol may play a protective effect, and the effect only exists in a certain period of time.