Potential cerebrovascular protective functions of lycium barbarum polysaccharide in alleviating hyperglycemia-aggravated cerebral ischemia/reperfusion injury in hyperglycemic rats.

Abstract

Lycium barbarum polysaccharide (LBP) is the efficient primary compound of Lycium barbarum and has been shown to alleviate hyperglycemia-aggravated cerebral ischemia/reperfusion (I/R) injury. However, the cerebrovascular changes related to diabetes mellitus (DM) and the potential cerebrovascular protective effects of LBP are still unknown. This study aimed to explore the cerebrovascular protective functions of LBP on cerebral I/R injury in diabetic rats and its potential mechanisms. Sprague Dawley (SD) rats were separated into three groups: the normoglycemic (NG), diabetic hyperglycemic (HG), and HG + LBP (50 mg/kg) treatment groups. A 30 min transient middle cerebral artery occlusion (tMCAO) with 24 h reperfusion was established. The neurological deficits, cerebral water content, infarct volume, and cerebrovascular permeability were assessed to evaluate the extent of cerebral injury. Histopathological alterations were assessed by hematoxylin and eosin, Nissl, immunohistochemical, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. A transmission electron microscope was used to detect ultrastructural alterations, and a western blot was used to examine protein expression. The HG rats exhibited a significant increase in neurological deficits, cerebral water content, infarct volume, cerebrovascular permeability, neural cell death, and apoptosis compared with the NG rats, and the LBP treatment alleviated these effects. Cerebrovascular structure analysis showed that the cross-sectional area (CSA) and wall thickness were remarkably altered in the HG rats compared with the NG rats. The LBP treatment protected the cerebrovascular structure and vasoreactivity by decreasing the wall thickness and increasing the CSA, α-smooth muscle actin, and endothelial nitric oxide synthase expression of cerebral vessels. The intake of LBP benefits the cerebrovascular structure and vasoreactivity in diabetic rats. Our research provides a possible new strategy for treating stroke in patients with DM.