The Expression Changes In IKK-NFκB/IκB Passageway And Anti-apoptotic Effect Of Tan ⅡA On Brain Tissue Of MCAO Model Rats

Objective:Study the pathogenesis of ischemia-reperfusion injury to look for an effective treatment method. Explore the possible anti-apoptotic mechanism of Tan Ⅱ A.Methods:The middle cerebral artery occlusion(MCAO) model was established by suture method, and combined with intraperitoneal injection of different time and dose Tan Ⅱ A. TTC staining and HE staining were completed, and the morphological changes in model groups and Tan ⅡA intervention groups were observed in brain tissue of ischemia-reperfusion injury. The expression levels of IKK and p-IKK、NFκB and p-NFκB、IκB and p-IκB were detected by western blot and immunohistochemistry and apoptosis was observed by Tunel to analysis the expression changes after ischemia-reperfusion injury and different time and dose Tan ⅡA treatment.Results:1.After TTC staining, we found that there was not infarct area in the sham group, while varying degrees of cerebral infarction was observed in the model and treatment groups. Tan ⅡA can reduced the infarct size.2.After HE staining we found that the structure was integrity in normal and sham groups, while the rest groups had varying degrees of histopathological changes, especially in7d model group, showing the infarct zone structural disorder, interstitial edema, inflammatory cell infiltration and cribriform necrosis. Ischemic changes in Tan ⅡA treatment groups were significantly improved compared with the model groups, which was most obvious in high dose Tan ⅡA intervention.3. IKK、NFκB and IκB expression in model groups and Tan II A treatment groups were significantly higher than in normal and sham groups(P<0.05). The expression between model groups and Tan ⅡA treatment groups had no significant difference (P>0.05). Compared with normal and sham groups, the expression levels of p-IKK、p-NFκB and p-IκB were significantly decreased in the model groups(P<0.05), Tan ⅡA treatment statistically upregulated the expression compared with the corresponding model group, and high and low does Tan ⅡA treatment groups also had statistically significant difference (P<0.05).4. Tunel showed that ischemia-reperfusion injury can increase apoptotic cells, especially in7d model group, and the difference was statistically significant between model groups and normal or sham group(P<0.05). Tan ⅡA intervention can significantly reduce apoptotic cells according to model group(P<0.05), and the difference between high and low does Tan ⅡA treatment was statistically significant(P<0.05). Conclusion: Ischemia-reperfusion injury of brain tissue can cause serious damage, structural disorder, inflammatory cell infiltration and increased apoptotic cells. Tan ⅡA treatment can improve this ischemia-reperfusion injury and reduce the number of apoptotic cells, and plays an important role in anti-apoptotic effect. The possible anti-apoptotic mechanism of Tan ⅡA maybe to stop the factors in IKK-NFκB/IκB passageway entering the nucleus and induce the expression of downstream apoptosis-related genes.This paper include12charts、4tables and35references.