| Background： Controlled hypotension is a commonly anesthetictechnique that used in clinical. At present,it is considered that sustainingthe MAP(50-55mmHg) is a safe lower limit of controlled hypotension.Within this range, the autoregulation of cerebral blood flow and perfusionof brain tissue remain action wells,there will be no ischemia-hypoxiainjury. But that process was only limit in1-2hours, with the continuousdevelopment of surgery, however, a major and complex surgery (such asorthopedic surgery) requires5-6hours and controlled hypotension thatalways indispensable in it.Whether continues controlled hypotensionwould lead to irreversible brain injury,is rare reports now.Cerebral hypoxic-ischemic injury is a complex process of pathologicalchange, a large number of studies indicated that massive white blood cellinfiltration is an important incentive to cause brain tissue damage,and theinfiltration of leukocyte is related to intercellular adhesion molecule (ICAM-1).As the proinflammatory cytokines, TNF-α and IL-1β plays animportant role in the inflammatory response, taken by inhibiting nuclearfactor (NF-kB) to make mononuclear macrophages and other cellssecreting more ICAM-1, IL-6,IL-8.the expression of ICAM-1upregulates that make leukocyte rolling and gathering in the endothelialcells.and make the ischemic injury of brain tissue further deteriorationthrough the release of the excitatory amino acid, calcium overload,formation of free radical, change of vasoconstriction and micro-thrombusformation.Numerous studies indicated that in heat shock andischemia-reperfusion rat model induce cerebral ischemic injury, theexpression of TNF-α were significantly increased, which indicated theover expression of TNF-α involved in the pathogenesis of cerebralischemia and reperfusion injury. There are studies reported that transientcerebral ischemia induce the upregulation of IL-1β, and give injections ofIL-1β antibody or IL-1β receptor blockers reduce the hypoxic-ischemicinjury of brain tissue.Objective： This study aims to observe the tolerance of sodiumnitroprusside combined with esmolol induced hypotension at differenttimes with the MAP sustain in50-55mmHg in rats,and the mechanism ofbrain injury with continued hypotension in rats.Methods：Male Sprague-Dawley rats were randomly divided into fivegroups(n=6),①blank group，Group A②operation control group， Group C③controlled hypotension group, Group H, and according toschedule is divided into three groups, H1(2h), H2(4h), and the H3(6h).Hypotension induced by sodium nitroprusside combined with esmolol tosustain the MAP in50-55mmHg for different times. During thestudy,montiored the MAP and HR of the rats and observed the blood gasanalysises, before and after the study, take1ml arterial blood forcentrifugation and save serum samples, after24hours,observedneurological serverity score after study for24hours, Evaluated theexpression ofTNF-α and IL-1βof hippocampal CA1region and serum byimmunohistochemical and ELISIAResults：1.The survival rate of group A、 C、H1and H2of stydy were100%after24hours,while the survival rate of the group H3was50%,andthe neurological severity scores of group H3compared with the first fourgroups was higher, there were statistic difference (P <0.05).2.The comparison of the concentration of TNF-α and IL-1β inserum between control group and hypotensive groups: the results ofELISA in preoperative serum,group C and group H were not statisticallysignificant (P>0.05). While the results of ELISA in postoperativeserum,the comparsion of group C and H2、H3,the differences werestatistically significant (P <0.05); the comparsion of group H3and H2、H1, the differences were statistically significant (P <0.05); the differenceof group H2and group H1was statistically significant (P <0.05). 3.The analysis of immunohistochemical staining of theexpression of TNF-α and IL-1β in the hippocampal CA1region: therewas no obviously positive expression in group A;there were positive cellsscattered in the group C and group H1;group H2and group H3showednumerous positive cells with brown-yellow staining particles in thecytoplasm.Conclusions：1.After hypotension(MAP50-55mmHg)continued for6hours in rats,compared with other groups,the NSS and survival ratedescended.2. After hypotension(MAP50-55mmHg)continued for6hours,the concentrations of TNF-α and IL-1β in the postoperative serumwere elevated,compared with group H2,the change was moresignificant.This indicated that the rats had a hypoxic-ischemia injury in acertain extent.3. After hypotension(MAP50-55mmHg)continued for4hours,the expression of TNF-α and IL-1β in the hippocampal CA1regionwere upregulation,while continued for6hours,there were strongerexpression,this indicated the brain showed an ischemia injury in a certainextent. |
PDF Full Text Request