| Implications and objectivePostoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within six months or postoperative institutionalization. POCD has also been associated with increased mortality, risk of losing ability to work prematurely, and heavier burden on the society and families. Postoperative delirium tends to first be observed in one to three postoperative days, while up to twenty-five percent patients tend to experience a postoperative cognitive dysfunction in one postoperative week. To date, the etiology of PD and POCD remains unclear, but aging is considered as one of the riskiest factors. Previous studies show that cognitive dysfunction of the aged people is closely related to the brain injury induced by oxidative stress, and some geriatric neurological diseases were mediated by advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGE). This study applies colorimetry, RT-PCR, immunohistochemical method to observe the impact of isoflurane and operation upon the oxidative stress in rat's brain, the changes of AGEs and RAGE expression in hippocampus. At the same time, the author applies Morris water maze to test learning and memorizing ability of rats after operation and anesthesia, which lays a foundation for the study on mechanism of postoperative cognitive impairment.Materials and methodsHealthy male SD rats, rats of 20 months old, rats of 4 months old, were randomly divided into six groups: elderly control group (N1); elderly isoflurane anesthesia group (A1); elderly operation group (B1 ); adult control group (N2); adult isoflurane anesthesia group (A2); adult operation group (B2); In A1 and A2 groups rats were anesthetized with 1.5% isoflurane for 2 hours. In B1 and B2 groups rats underwent laparotomy in condition of 1.5% isoflurane anesthesia for 2 hours .As a comparison, rats in N1 and N2 groups breathe 30% oxygen and air mixed gas for 2 hours in Inhalation box. After 24 hours of anesthesia and operation, sixty rats were underwent Morris maze test, including place navigation test and spatial probe test, to observe the impacts of anesthesia and operation upon rat's learning and memorizing ability. Fouty-eight rats were executed after 24 hours of anesthesia and operation. Part hippocampuses and cerebral cortex drawn from died rats'brain were homogenized in order to detect the amount of MDA and SOD in the tissue by means of colorimetry, which is applied to compare the discrepancy of oxidative stress in groups. Part of the sample of rats'hippocampus were prepared for RT-PCR and immunohistochemistry to observe the changes of AGEs and RAGE expression.Results:1. The result of water maze test: Escape latency in A1 and B1 were longer than that in N1 on the forth and fifth days (P<0.05), and escape latency in B1 was longer than that in A1(P<0.05); escape latency in A2 group had no statistics difference with the comparison group on the forth and fifth days (P>0.05); escape latency in B2 was longer than N2 and A2 groups(P<0.05). The times of acrossing the original platform in A1and B1 were obviously less than N1 (average P<0.01), while time consumption was shorter than N1 (P<0.05). Compared to N2, A2 was no obvious difference between the time consumption of staying the original platform quadrant and the times of acrossing the original platform. The times of acrossing the original platform in B1 group was less than N2 and A2(P<0.01), and time consumption was shorter (P<0.05).2. Index of oxidative stress: Compared to N2, the level of SOD in N1 was lower but the level of MDA was higher. The level of SOD in old rats treated with isoflurane and operation declined and further with accelerated level of MDA. The change of B1 is most obvious, particularly compared to N1, A1 (P<0.05). Compared to N2, the oxidative stress in A2 appears higher (P<0.05). The level of SOD in B2 declined apparently,but MDA accelerated. There were sharp differences between B2 and the comparison & isoflurane groups(P<0.01). 3. AGEs expression: The level of AGEs in N2 was the merest, the same level in A2 and N2, but obvious elevation in B2 compared to N2 and A2 (P<0.05). In the elderly groups,the level of AGEs increased to some degree after anesthesia and operation, with B1 the most significant compared to N1 and A1 (P<0.01).4. RAGE expression: Compared to the result of mRNA, there was an obvious elevation in terms of RAGE expression in A1 and B1 groups, with B1 the most (P<0.05). There was slight elevation in A2, but significantly in B2, higher than N2 and A2. According to the result of RAGE protein expression, the amount of RAGE in A1 and B1 had a tendency to increase, obvious when compared to N1 (P<0.05). The results in A2 and N2 were similar, and higher in B2 when compared to A2, N2 (P<0.05).Conclusions:1. The 1.5% isoflurane results in the declining ability to learn and memorize for old rats, but the impact is more significant when after operation; In this respect, under 1.5% isoflurane inhalation anesthesia ,there is no obviosly harm to adult rats. Operation result in cognitive impairment to adult rats.2. Isoflurane and operation result in the elevation of oxidative stress in rat's hippocampus and cerebral cortex, which appears more obvious in the old rats group. Isoflurane and operation both lead to the elevation of AGEs and RAGE expression in old rats, only operation do for adult rats.3. The enhancement of oxidative stress caused by isoflurane and operation and the changes of AGEs and RAGE expression are likely to be one of the reasons of animals'declining ability to learn and memorize... |
PDF Full Text Request