Abstract: Objective To study the role of reduced form of nicotinamide adenine dinucleotide phosphate(NADPH) oxidase 4 (NOX4) in pituitary adenoma hemorrhagic stroke(pituitary apoplexy,PA). Methods Specimens were collected from the remaining specimens of pituitary adenoma surgery in the Department of Neurosurgery, Zhongshan Hospital Affiliated to Xiamen University. According to postoperative pathology, the specimens were divided into hemorrhagic stroke(PA) group and non-stroke(non-PA) group, and 18 cases were selected from each group. Hematoxylin eosin (HE) staining was used to determine whether hemorrhage. The percentage of NOX4 positive cells was detected by immunohistochemical staining. The expression of NOX4 protein was detected by Western blot. DCFH-DA probe was used to detect the fluorescence intensity of reactive oxygen species (ROS). Apoptosis rate was detected by TUNEL. Results There was a large number of erythrocytes exuded between tissues in the hemorrhagic stroke group, but no red blood cell was found in the non-stroke group. The percentage of NOX4 positive cells in hemorrhagic stroke group (21.53%±4.25%) was significantly higher than that in non-stroke group (4.29%±1.71%) (P<0.001). The expression level of NOX4 in the hemorrhagic stroke group was significantly higher than that in the non-stroke group (P<0.001).The mean fluorescence intensity of ROS in hemorrhagic stroke group was significantly higher than that in non-stroke group(P<0.001). The percentage of apoptotic cells in hemorrhagic stroke group (38.64%±12.46%) was significantly higher than that in non-stroke group (6.19%±2.40%) (P<0.001). Conclusions NOX4 is involved in the occurrence of pituitary adenoma hemorrhagic stroke. NOX4-mediated oxidative stress regulation of apoptosis is found to be potential mechanism of hemorrhagic stroke in pituitary adenomas.

Key words: NADPH oxidase 4 (NOX4), pituitary adenoma, hemorrhagic stroke, oxidative stress, apoptosis