Neuroprotective mechanism of HIF-1α overexpression in the early stage of acute cerebral infarction in rats

摘要

The present study aimed to explore the expression and neuroprotective mechanism of hypoxia inducible factor (HIF-1α) in the brain tissue of a rat model of early acute cerebral infarction. A total of 64 Sprague Dawley rats were randomly divided into surgery and sham groups and the model of focal cerebral infarction was established by the suture-occluded method. In the sham group, blood vessels were separated but not occluded. Rats in the surgery and sham groups were subdivided into eight groups (n=4/group). Blood samples was collected at 8 time points including 30 min and 1, 3, 6, 12, 48, 24 and 72 h, respectively, and HIF-1α content was detected using ELISA. Brain tissues of rats in all groups were harvested following blood collection. HIF-1α protein expression was detected by immunohistochemistry and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to analyze the brain cell apoptosis index. ELISA results demonstrated that rats in the surgery group began to express HIF-1α within 30 min, and HIF-1α expression levels gradually increased, peaking at 12 h. HIF-1α expression levels were significantly increased in the surgery group at all time points, as compared with the sham group (P<0.05). The concentration of HIF-1α decreased rapidly in 12 h. At various time points, HIF-1α protein expression in the brain tissue of rats in the sham group was negative. HIF-1α protein expression was significantly increased in the surgery group (P<0.05), peaking at 12 h, and decreasing after this point. As compared with the sham group, the apoptosis indices of the brain tissue of rats in the surgery group exhibited a gradual increasing trend with significant decreases observed after 12 h (P<0.05). Intra-group comparison of all indices in the surgery group, indicated that there was a statistically significant difference between postoperative 12 h and other time points (P<0.05). In conclusion, the present study demonstrated that HIF-1α was highly expressed in the brain tissue of rat models of early acute cerebral infarction. The results also indicated that HIF-1α significantly reduced the apoptosis of infarcted cells, suggesting that HIF-1α may have a neuroprotective role in early acute cerebral infarction.