Protective effect of hydroxysafflor yellow A alone or in combination with acetylglutamine on cerebral ischemia reperfusion injury in rat: A PET study using 18F-fuorodeoxyglucose

Abstract

Hydroxysafflor yellow A (HSYA) and acetylglutamine (NAG) are extensively applied in the treatment of brain injury. In this study, we investigated the neuroprotective effect and underlying mechanism of HSYA alone or together with NAG using a rat model of cerebral ischemia reperfusion injury. Male Sprague-Dawley (SD) rats (n = 5) were intraperitoneally injected with 5, 10, 20 mg/kg HSYA, 300 mg/kg NAG and 10 mg/kg HSYA+300 mg/kg NAG after the onset of reperfusion and once each day for the following 7 days. After assessing the neurological deficit and infarct volume, we used 18F-FDG-PET to evaluate the regional cerebral metabolic rate of glucose consumption, immunohistochemical analysis to detect the expression of GFAP, NGF, Bcl-2, Bax, caspase-3 and ICAM-1 in brain tissue at day 7 after cerebral I/R injury. Meanwhile, the mRNA levels of ICAM-1, IL-1ß, TNF-α and NF-κB were determined by qRT-PCR, the protein levels of Bcl-2, Bax and caspase-3 were detected by western blot. The results indicated that HSYA significantly up-regulated glucose metabolism, improved neurological function, decreased cerebral infarction volume. HSYA alone or together with NAG attenuated apoptosis and inflammation by up-regulating GFAP, NGF and Bcl-2 expression, suppressing the expression of Bax, caspase-3 and ICAM-1, IL-1ß, TNF-α and NF-κB. These finding suggested that HSYA exerted neuroprotection against cerebral I/R injury by modulating inflammation and apoptosis process, and HSYA in combination with NAG possessed a synergetic effect on protecting cerebral I/R brain injury.