Effect of mitochondrial cytochrome c release inhibitor on the inflammatory response of rats with global cerebral ischemia reperfusion injury

ObjectiveTo explore the effects of mitochondrial cytochrome c inhibitor on the cerebral injury in rats with global cerebral ischemia-reperfusion injury, and analyze the possible mechanisms of mitochondrial aldehyde dehydrogenase 2(ALDH2)and inflammatory response.

MethodsThe rat model with global cerebral ischemia and reperfusion injury(I/R) was simulated by four-vessel occlusion.The male SD rats were randomly divided into the sham group, I/R group and ALDH2 agonist Alda-1+I/R group and Bax-mediated mitochondrial cytochrome c release inhibitor(Bcb)+I/R group.The HE staining was used to observe the morphological changes of hippocampal CA1 cells.The expressions of ALDH2 protein and inflammasome-related protein NLRP3 in hippocampal CA1 were observed by immunohistochemistry.The protein changes of 4-HNE, NLRP3, IL-1β, IL-18 and ALDH2 in hippocampal CA1 were detected by Western blotting.

ResultsCompared with the sham group, the survival rate of hippocampal CA1 region cells in the I/R group decreased significantly after 7 d of reperfusion(P < 0.01).Compared with the I/R group, the survival rate of hippocampal CA1 neurons in ALDA-1 +I/R group and Bcb+I/R group increased(P < 0.01).Compared with the I/R group, the expression of ALDH2 protein increased in Bcb+I/R group and ALDA-1 +I/R group, while the expressions of NLRP3, IL-1β, IL-18 and 4-HNE proteins in hippocampal CA1 region decreased(P < 0.01).

ConclusionsThe expression of NLRP3 in hippocampal CA1 increases in rats with global cerebral I/R injury model.The Bcb may play a protective role by promoting the mitochondrial ALDH2 expression and reducing inflammatory response.