ABSTRACT
Drugs for the treatment of central nervous system diseases need to enter the brain tissue through the blood-brain barrier to function. In high altitude hypoxic environment, there are changes in tight junction proteins of blood-brain barrier tissue structure, transporters in astrocytes and endothelial cells and ATP in endothelial cells; at the same time the permeability of the blood-brain barrier is increased. These changes are an important reference for rational drug use in patients with central nervous system disease in the plateau region. This article reviews the research progress on the effects of plateau hypoxia on the structure of the blood-brain barrier and related drug permeability.
ABSTRACT
OBJECTIVE: To investigate the effects of high-altitude hypoxic environment on the expression of pregnane X receptor (PXR) in rat liver and related mechanism. METHODS: Wistar rats were randomly divided into five groups with 8 rats in each group, the rats were exposed to high-plateau hypoxia for 0 (control group), 12, 24, 36 and 48 h, respectively. Abdominal aortic blood samples were collected for blood gas analysis. HE staining was used to observe the pathological changes of liver tissue. The expression levels of PXR mRNA in liver tissues were determined by RT-PCR. Western blot analysis was performed to determine the protein expression of PXR and protease SUG1 in liver tissues of rats. RESULTS Compared with the control group, the blood pH of the rats decreased after 12 h of acute hypoxia. After 24 h exposed to hypoxia, SaO2 was lower than 80%, PaO2 was lower than 60 mmHg (1 mmHg=0.133 kPa); and PaCO2 increased after 48 h exposed to hypoxia (P<0.05). There was obvious edema in the central vein of the liver tissue at 12 h and 24 h after exposure to hypoxia. The liver tissue of the rats exposed to hypoxia for 36 h and 48 h showed inflammatory infiltration. The expression of PXR mRNA was significantly decreased by 63%, 96%, 86%, and 85%at 12, 24, 36 h, and 48 h after exposure to hypoxia (all P<0.05), respectively. The protein expression of PXR was significantly up-regulated by 93%and 99%after 36 h and 48 h exposure to hypoxia (all P<0.05), respectively. The protein expression of proteinase SUG1 decreased by 14%, 34%and 46%after 24, 36 and 48 h after hypoxia (all P<0.01). CONCLUSIONS Acute hypoxia at high altitude can affect the expression of nuclear receptor PXR in rat liver, and protease SUG1 may be a regulatory factor for PXR expression in hypoxia.