Expression And Prognosis Of Plasma HMGB1in Rabbits With Delayed Neuropsychological Sequelae

Objective：Observed changes of high mobility group protein1(HMGB1) of rabbitswith acute CO poisoning dynamically，to discuss on possible mechanism of HMGB1in the course of delayed neuropsychological sequelae(DNS)；Meanwhile，observedeffects of its antagon--sodium butyrate on blood circulation of rabbits with acutecarbon monoxide poisoning，and to explore possible mechanism of brain protection.Methods:①Twenty-four healthy male rabbits were randomly divided into A，B，Cthree groups，n=8. A，control group；B，DNS group；C，intervention group，sodiumbutyrate was given by500mg/kg from ear vein ten minutes before preparing model.Purity CO gas was injected to rabbit intraperitoneal，to prepare the model of delayedneuropsychological sequelae，in the end of modeling，1hour，3hours，6hours，12hours，24hours，3days，7days，14days，21days，draw blood from ear vein eachtime to test levels of HMGB. Collected blood until21th day，take the brain afteranesthetizing，HE staining.②Take another24similar rabbits，also randomly dividedinto D，E，F three groups，n=8. D，control group；E，acute CO poisoning group；F，intervention group；Intervention methods of E、F group were same to B，C group’.Modeling until7th day，test each index of hemorheology and platelet aggregation rate.Results:①The performance of rabbits with acute CO poisoning：B group died oneeach at6hour and12hour，C group died one at6hour，E group died two at8hour，no death in A，D and F groups.②Brain pathology showed：pathological brain tissueof B group undergoinged damage extensivly，the most obvious pathological changesin the hippocampus and cortex，a large number of neuronal degenerated and necrosisor apoptosis，normal neurons almost disappeared；degeneration and necrosis nerve inthe hippocampus and cortex of C group compared with B group’ decreasedsignificantly. According to brain biopsy later，a large number of degeneration andnecrosis or apoptosis neurons in the hippocampus stands for success for replication the DNS model. In this study，on21th day，B group all changed to DNS，C group onlyone case changed to DNS.③HMGB1test showed: three hours in ending ofmodeling，HMGB1levels of B group compared with A group’ different (P<0.05).From6th hour to21th day，between B group’ and A group’ were differencessignificant (P<0.01)，while C group’ than A group’ not different (P>0.05). From6thhour to21th day，rabbits(B and C group) with CO poisoning finally form to DNSgroup compared with no DNS group also different significantly (P<0.01).④Hemorheology showed: high，middle and low shear rate of whole blood viscosity，plasma viscosity，FIB，and Hct of E group were higher than the D group’ significantly(P <0.01)；Those indexes of F group was significantly lower than E group’(P <0.01)，and compared with D group’ no significant difference(P>0.05).⑤Platelet aggregationshowed：platelet aggregation rate within1th minute，3th minute，5th minute of Egroup was higher than D group’ significantly；platelet aggregation of F groupcompared E group’ within1min decreased (P <0.05)， aggregation rate within3thminute，5th minute decreased significantly (P <0.01)，while compared with D group’no significant statistically difference.Conclusion:1. HMGB1-mediated inflammatory response played an important role inthe formation of DNS，and early HMGB1levels in plasma of DNS group increasedsignificantly，being gived its antagonist could improve prognosis，then HMGB1maybecome a new early clinical warning indicator and potential therapeutic target to DNS2. After acute CO poisoning，hemorheology and platelet aggregation rate all changedsignificantly，leading to form to blood clots easily，hinting that cerebral circulationdisorders may be an important reason for leading to DNS.3. Sodium butyrate could improve cerebral circulation disorders of rabbits with acuteCO poisoning significantly，and its mechanism was most likely by through inhibitingacetylation of HMGB1，blocking inflammation-coagulation network，hinting thatHMGB1may be an important link between coagulation and inflammation.