Research Of The Effect Of Endoplasmic Reticulum Stress During Deep Hypothermic Circulatory Arrest In Rats Brain Hippocampal Neuronal Cells

[Objective] Deep hypothermic circulatory arrest(DHCA)is a common technique used in aortic arch surgery and in the correctional surgery of complex pre-heart disease.DHCA provides a bloodless field of view for surgical operations by interrupting circulating blood flow,completes surgical goals,and protects the nervous system from ischemic-hypoxic damage by reducing cellular metabolic rate through controlled hypothermia.However,hypothermia and disruption of blood flow in DHCA can still lead to postoperative neurological complications,such as seizures,cognitive deficits,hyperactivity and behavioral disorders.In this study,we proposed to establish an animal model of DHCA in rats,and to investigate whether DHCA induces ERS in brain tissue by measuring the difference in GRP-78 expression in hippocampal nerve cells between Sham and DHCA group.To study the effect of endoplasmic reticulum stress during deep hypothermic circulatory arrest in rats brain hippocampal neuronal cells.[Methods] Twenty-four SD rats were taken and randomly divided into two groups: the Sham group(N = 12)and DHCA group(N = 12).The rats were weighed and anaesthetized by inhalation.After successful anaesthesia,the rats were fixed on a small animal heating blanket and the skin was prepared on the neck,right thigh root and tail root.Connected animal vital signs detection equipment to monitor respiratory rate,heart rate,electrocardiogram and core temperature in rats.The jugular vein and the tail artery cannula were used to establish the animal model of closed chest cardiopulmonary bypass(CPB)in rats.Systemic heparinization by infusion of heparin in the caudal artery.The DHCA group started CPB transfer after the above operation,observed whether the jugular venous drainage was smooth and prevented the venous drainage tube placed in the right atrium from negative pressure,confirmed the drainage was smooth and gradually increased the flow to the target perfusion rate,and the extracorporeal membrane lung was oxygenated by an oxygen mixing device.The DHCA group confirmed smooth jugular venous drainage and then transferred to the machine for 5 minutes to start cooling,the core temperature was lowered to 17°C for 30 minutes,DHCA was induced at 17°C core temperature for 45 minutes,and cardiac blood was evacuated by jugular venous cannulation during cardiac arrest in the DHCA group,and the core temperature was restored to 36°C for 40 minutes after DHCA.Rats in the Sham group did not conduct CPB and DHCA after establishing cannula.During this period,the blood oxygen content and related indicators of rats were recorded.After cardiopulmonary bypass,the decapitation was executed by euthanasia to take the cortex of the frontal parietal lobe of rat brain.Specimens were preserved in liquid nitrogen.The protein of the cerebral cortex of rats was extracted for the protein detection of the expression level of glucose-regulated protein 78 by using Western Blot.The data obtained from the experiment was expressed by using mean + standard deviation,and a one-way ANOVA with complete random design was used.For the comparison between multiple sample means,the t test was used.P <0.05 indicated that the difference was statistically significant.[Results] The GRP-78 expression compared with β-actin of DHCA group(n=12)is 1.37±0.06,The GRP-78 expression compared with β-actin of Sham group(n=12)is 1.08±0.04.Compared with the Sham group,the expression of GRP-78 in DHCA group was significantly increased.The difference was statistically significant(t=14.200,P=0.000**).[Conclusion] Deep hypothermic circulatory arrest can induce the increase of the expression of glucose-regulated protein 78 in rats hippocampal neuronal cells,hints that DHCA may induce endoplasmic reticulum stress.