The Protective Effects Of Ischemic Postconditioning On Deep Hypothermic Circulatory Arrest Rats And Its Mechanism

[Background]Deep hypothermic circulatory arrest (DHCA) is an important protective technology in cardiovascular surgery. It is widely used in cardiac surgery and aortic surgery in children with complex congenital heart surgery. Effect of complex surgical treatment of cardiovascular disease was improved significantly since this technology was applied to clinical. But because of long operative time, cerebral ischemia and low flow perfusion, ischemia and hypoxia and other factors, postoperative complication of the brain after DHCA is very high. How to prevent the brain injury after DHCA becomes focused in recent years.Ischemia Postconditioning (I-postC) is a newly discovered endogenous protection. After a longer period of ischemia, carrying out a short reperfusion/ ischemia cycle before reperfusion can reduce the reperfusion injury and achieve the protective effect of tissues and organs. As a new measures fighting against ischemia-reperfusion injury, the current studies have shown that I-postC can decrease the heart, brain, liver, kidney, spinal cord and other organs or tissue ischemia, thereby reducing its barrier function. Many recent studies showed that I-postC could reduce inflammation and improve the oxygen free radicals, reduced neuronal apoptosis in brain tissue effectively, protect cell function through a variety of mechanisms. Meanwhile, numerous studies have indicated that cerebral ischemia-reperfusion injury related mainly with oxidative stress, inflammation and cell apoptosis. Neuronal apoptosis is the important part in brain ischemia-reperfusion injury.Ⅰ-postC technique is simple and easy to operate, therefore,Ⅰ-postC applied to brain protection after DHCA has a good prospect and worthy of further research.[ Objective]To observe the protective effects of theⅠ-postC for brain tissue of DHCA rats. To explore the possible mechanism of this protective effect through the establishment of DHCA model, testing brain tissue related indicators, the ultrastructure of rat brain and neuronal apoptosis.[Materials and Methods]60 adult male clean SD rats were randomly divided into 5 groups:the sham group, DHCA group and IPostⅠgroup, IPostⅡgroup and IPostⅢgroup. Use the improved "four-vessel method" to produce global cerebral ischemia model of DHCA rates. After the modeling, exposed the sham operation group without vascular coagulation and clipping. Rats in DHCA group opened up without any treatments after blocking for 45 minutes later. IPostⅠgroup:before the opening hours repeated the cycle "open 15s/block 15s" for three times and then fully opened. IPostⅡgroup:before the opening hours repeated the cycle "open 30s/ block 30s" for three times and then fully opened. IPostⅢgroup:before the opening hours repeated the cycle "open 60s/block 15s" for three times and then fully opened. Animals were killed at reperfusion 24 hours, then make the rats'brain tissue homogenate, inflammatory cytokines TNF-α, IL-1βand IL-6 were detected; and then SOD activity and MDA of this homogenate were detected; ultrastructural changes in brain tissue was observed under electron microscopy; hippocampal and cortical neurons apoptosis were detected by TUNEL.[Results]Compared with DHCA group, inflammatory cytokines TNF-α, IL-1βand IL-6 of IPostⅠgroup and IPostⅠgroup and IPostⅡgroup decreased significantly (P<0.05, P<0.01), inflammatory cytokines TNF-α, IL-1βand IL-6 of IPostⅢgroup showed no significant difference (P>0.05). Compared with DHCA group, SOD activity of IPostⅠgroup increased significantly (P<0.01), SOD activity of IPostⅡgroup increased significantly (P<0.05). MDA in IPostⅠgroup and IPostⅡgroup decreased significantly (P<0.05). After 24 hours of reperfusion, SOD,MDA expression of IPostⅢwas not statistically significant compared with DHCA group. The brain tissue pathology display, Compared with DHCA group, ischemic postconditioning group brain histoclasia and cell injury is obviously lighten.Pathology results showed that:the brain tissue damage and cell injury of IPostⅠgroup and IPostⅡgroup were significantly lower than DHCA groups, the brain tissue damage and cell injury of IPostⅢgroup was similar with the DHCA group Hippocampus and cerebral cortex neural cell apoptosis detected:apoptotic index in IPostⅠgroup and IPostⅡgroup significantly reduced compared to the DHCA group.[Conclusions] Eraly ischemic postconditioning(15s,30s) can reduce the inflammatory response, improve the metabolism of oxygen free radicals and reduce the apoptosis of brain cell, can protect the brain of DHCA rats.