Diabetes mellitus aggravates cerebral ischemia-reperfusion injury in rats by inflammatory response

Abstract

Objective To investigate the roles of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in cerebral ischemia-reperfusion injury in rats with diabetes mellitus. Methods Thirty-six healthy male Sprague-Dawley rats were divided into a euglycemic sham operation group, a euglycemic ischemia-reperfusion group, and a diabetes ischemia-reperfusion group (n=12 in each group) according to a random number table. A diabetes model was induced by intraperitoneal injection of streptozotocin, and then a focal cerebral ischemia-reperfusion model was induced by the suture method. The neurological deficit score was performed at 24 h after reperfusion. 2, 3, 5 triphenyl tetrazolium staining was used to measure the cerebral infarction area. Western blotting was used to detect the expression levels of NF-κB and TNF-α on the ischemic sides. Results The neurological function scores were 0.00±0.00, 2.50±1.08, and 3.20±1.03, respectively in the euglycemic sham operation, euglycemic cerebral ischemia-reperfusion and diabetes cerebral ischemia-reperfusion groups, and there were significant differences (F=38.015, P<0.001). The neurological deficit scores of the diabetes cerebral ischemia-reperfusion group were significantly aggravated compared with the euglycemic cerebral ischemia-reperfusion group (P<0.05). The infarct areas of the euglycemic sham operation, euglycemic cerebral ischemia-reperfusion and diabetes cerebral ischemia-reperfusion groups were 0.00%±0.00%, 33.09%±5.17%, and 55.45%±9.29%, respectively, and there were significant differences among the groups (F=206.614, P<0.001), in which the infarct area in the diabetes cerebral ischemia-reperfusion group was enlarged significantly compared with the euglycemic cerebral ischemia-reperfusion group (P<0.05). At 24 h after reperfusion, there were no significant differences in the expression levels of the cortical NF-κB (F=29.993, P<0.001) and TNF-α (F=28.722, P<0.001) on the ischemic sides in each group, in which the expression levels of NF-κB and TNF-α in the diabetes cerebral ischemia-reperfusion group were increased significantly compared with the euglycemic cerebral ischemia-reperfusion group (all P<0.05). Conclusions Diabetes may aggravate cerebral ischemia reperfusion injury. The upregulated expression of TNF-α and NF-κB may be one of the mechanisms of diabetes aggravating cerebral ischemia-reperfusion injury. Key words: Brain Ischemia; Diabetes Mellitus, Experimental; Reperfusion Injury; Tumor Necrosis Factor-α; NF-κB; Inflammation; Rats