OBJECTIVE：To in vestigate the effects of dexmedetomidine （Dex）on SIRT 1/Akt/GSK3β/β-catenin signaling pathway in cerebral injury of sepsis model rats ，and explore the mechanism of its protecitve effect on cerebral injury. METHODS ： A total of 80 male SD rats were randomly divided into sham operation group （Sham group ），sepsis group （CLP group ），CLP+Dex group（10 μg/kg Dex），CLP+Dex+Sirtinol group （10 μg/kg Dex+2 μL/100 g SIRT 1 inhibitor sirtinol ），with 20 mice in each group. Two hours before modeling ，CLP+Dex+Sirtinol group was injected with sirtinol via lateral ventricle. Sepsis model was induced by cecal ligation and perforation in each group （in sham group ，only operation was performed but no ligation was performed）. At 0，3，6 h after modeling ，CLP+Dex group and CLP+Dex+Sirtinol group were given Dex （10 μg/kg） intraperitoneally，Sham group and CLP group were given constant volume of normal saline intraperitoneally. Cerebral tissue water content，Evans blue （EB）content，apoptosis in cerebral cortex ，the levels of IL- 1β and TNF-α in cerebral tissue as well as the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were detected 24 h after last medication. RESULTS ： Compared with Sham group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were increased significantly（P＜0.05），while the protein expression of SIRT 1， p-Akt，p-GSK3β and β-catenin in hippocampus were decreased significantly （P＜0.05）. Compared with CLP group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were decreased significantly in CLP+Dex group （P＜0.05），while the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were increased significantly （P＜0.05）. Sirtinol could significantly reverse the above-mentioned cerebral protection and factor regulation effects of Dex （P＜0.05）. CONCLUSIONS ：Dex can protect the cerebral tissue of sepsis model rats，which may play an anti-inflammatory and anti-apoptotic role by activating SIRT 1/Akt/GSK3β/β-catenin signaling pathway ，so as to reduce cerebral edema ，protect blood-brain barrier and reduce cerebral injury.

Objective To explore the role of apoptosis-inducing factors (AIF) mediated non-apoptosis classic pathway involved in neuron apoptosis of rats with chronic fluorosis.Methods Sixty Sprague Dawley (SD) rats (body weight 100-120 g) were divided into two groups (30 rats in each group,half male and half female) by random number table according to body weight.Control group was fed with tap water with fluoride content ＜ 0.5 mg/L and fluorine group was fed with water with fluoride content of 50.0 mg/L.Both groups were fed with standard food with fluorine content ＜ 0.5 mg/kg.After 10 months,all the animals were sacrificed though heart perfusion using phosphate buffer,and brain tissue was taken.Immunohistochemical method was employed to detect the distribution of AIF in brain tissue.Western blotting was used to test the protein expression of AIF,cl-caspase-3 and cl-caspase-9.Flow cytometry was used to examine apoptosis rate.Results The AIF positive distribution and degree of staining in the neurons of hippocampal CA1,CA2 and CA3,as well as the parietal cortex (7.50 ± 2.17,9.00 ± 1.63,8.00 ±0.82,10.24 ± 1.80) in rats with chronic fluorosis were significantly higher than those of the control group (5.18 ±1.66,6.27 ± 1.42,6.36 ± 1.96,6.96 ± 2.62,t =2.76,4.09,2.45,5.77,all P ＜ 0.05).The AIF protein expression of neuronal mitochondria in the cerebral tissue of rats with chronic fluorosis [(89.46 ± 8.47)％] was significantly lower than that of the control group [(100.00 ± 7.12)％,t =3.16,P ＜ 0.01],while the AIF protein expression of the neuronal nucleus [(112.80 ± 7.10)％] was significantly higher than that of the control group [(100.00 ± 8.20)％,t =3.75,P ＜ 0.01];cl-caspase-3 and cl-caspase-9 protein expression in the neurons of hippocampus and cortex from the rats with chronic fluorosis [(132.14 ± 18.66)％,(107.31 ± 2.58)％,(121.33 ± 14.86)％,(112.97 ± 7.97)％]were significantly higher than those of the control group [(100.00 ± 11.99)％,(100.00 ± 3.74)％,(100.00 ± 16.87)％,(100.00 ± 8.04)％,t =3.55,3.94,2.32,2.81,P ＜ 0.01 or ＜ 0.05].As compared with those of the control group [(1.28 ± 0.59)％,(1.88 ± 0.25)％],the apoptosis rates in hippocampus and cortex of the rats with chronic fluorosis [(2.55 ± 0.58)％,(3.05 ± 0.65)％] were significantly increased (t =3.08,3.40,all P ＜ 0.05).Conclusion Both of AIF-mediated caspase-independent apoptosis and the classic caspase-dependent apoptosis pathways have participated in neuron apoptosis in rat induced by chronic fluorosis,which may be one of the mechanisms of brain damage of the disease.

Objective Metabolomics and radioimmunoassay technologies were used to analyze the effects of acceleration exposure on the levels of human serum metabolites , stress-related hormones and such gastrointestinal regulatory factors as resistin and leptin , so as to provide new scientific evidence for the mechanism of gastrointestinal symptoms in motion sickness .Methods Sixty volunteers were recruited and exposed to abnormal acceleration for 15 minutes by using a 6-degree-of-freedom ship motion simulator .The severity of motion sickness was measured by Graybiel Scale; gas chromatography coupled with time-of-flight mass spectrometry ( GC-TOF/MS ) was used to detect serum metabolites in the human subjects; serum glucocorticoid, adrenaline, arginine vasopressin ( AVP ), insulin, resistin and leptin were detected by radioimmunoassay and ELISA .Results ( 1 ) The incidence of motion sickness was 72%.( 2 ) Acceleration exposure could induce significant changes in the levels of serum metabolites in the subjects , of which glucose and N-dodecanoic acid levels were significantly higher than those before exposure , while L-serine and L-threonine levels were significantly decreased after exposure (P<0.05).(3) Acceleration exposure could cause decrease in the level of serum insulin [ (21.03 ±6.78) mIU/L before exposure,(14.97 ±2.94)mIU/L after exposure], and increase in the level of glucagon , glucocorticoid, epinephrine and arginine vasopressin (AVP) [ (18.06 ±5.72)ng/L,(212.88 ±61.37)μg/L,(88.41 ±35.72)ng/L and(10.80 ±7.30)ng/L before exposure;(20.40 ±5.48)ng/L,(293.34 ±50.91)μg/L,(132.83 ±67.25 )ng/L and(51.35 ±8.24)ng/L after exposure] respectively(P<0.05 or P<0.001).(4) Acceleration exposure could also decrease the levels of gastric inhibitory peptide ( GIP), leptin,resistin, but increase the level of ghrelin [ (170.34 ±82.64) nmol/L,(744.03 ±438.46)μg/L,(6687.96 ±3289.18)μg/L and (136.43 ±74.75) ng/L before exposure;(41.05 ±17.91) nmol/L,(409.95 ±347.95)μg/L,(2615.56 ±1345.61)μg/L and (210.85 ±109.01) ng/L after exposure] respectively(P<0.05 or P<0.01).Conclusions Our study indicated that stress could be induced by acceleration exposure , resulting in significant changes in the levels of stress-related hormones and gastrointestinal regulatory factors , as well as serum metabolites .

Objective Metabolomics and radioimmunoassay technologies were used to analyze the effects of acceleration exposure on the levels of human serum metabolites , stress-related hormones and such gastrointestinal regulatory factors as resistin and leptin , so as to provide new scientific evidence for the mechanism of gastrointestinal symptoms in motion sickness .Methods Sixty volunteers were recruited and exposed to abnormal acceleration for 15 minutes by using a 6-degree-of-freedom ship motion simulator .The severity of motion sickness was measured by Graybiel Scale; gas chromatography coupled with time-of-flight mass spectrometry ( GC-TOF/MS ) was used to detect serum metabolites in the human subjects; serum glucocorticoid, adrenaline, arginine vasopressin ( AVP ), insulin, resistin and leptin were detected by radioimmunoassay and ELISA .Results ( 1 ) The incidence of motion sickness was 72%.( 2 ) Acceleration exposure could induce significant changes in the levels of serum metabolites in the subjects , of which glucose and N-dodecanoic acid levels were significantly higher than those before exposure , while L-serine and L-threonine levels were significantly decreased after exposure (P<0.05).(3) Acceleration exposure could cause decrease in the level of serum insulin [ (21.03 ±6.78) mIU/L before exposure,(14.97 ±2.94)mIU/L after exposure], and increase in the level of glucagon , glucocorticoid, epinephrine and arginine vasopressin (AVP) [ (18.06 ±5.72)ng/L,(212.88 ±61.37)μg/L,(88.41 ±35.72)ng/L and(10.80 ±7.30)ng/L before exposure;(20.40 ±5.48)ng/L,(293.34 ±50.91)μg/L,(132.83 ±67.25 )ng/L and(51.35 ±8.24)ng/L after exposure] respectively(P<0.05 or P<0.001).(4) Acceleration exposure could also decrease the levels of gastric inhibitory peptide ( GIP), leptin,resistin, but increase the level of ghrelin [ (170.34 ±82.64) nmol/L,(744.03 ±438.46)μg/L,(6687.96 ±3289.18)μg/L and (136.43 ±74.75) ng/L before exposure;(41.05 ±17.91) nmol/L,(409.95 ±347.95)μg/L,(2615.56 ±1345.61)μg/L and (210.85 ±109.01) ng/L after exposure] respectively(P<0.05 or P<0.01).Conclusions Our study indicated that stress could be induced by acceleration exposure , resulting in significant changes in the levels of stress-related hormones and gastrointestinal regulatory factors , as well as serum metabolites .