Objective To investigate the analgesic efficacy and spinal neurotoxicity of intrathecal (IT) different doses of dexmedetomidine in rats. Methods Sixty male SD rats weighing 180-220 g were randomly divided into 5 groups ( n = 12 each): groupnormal control (group C); group IT normal saline (group N); different doses of dexmedetomidine groups received IT dexmedetomidine 0.75, 1.50 and 3.00 μg/kg respectively (groups D1.3). Paw withdrawal threshold to mechanical stimulation (PWMT)with yon Frey filaments and tail flick latency (TFL) to a thermal nociceptive stimulus were measured before (To, baseline) and at 30 or60 rin after IT dexmedetomidine or normal saline administration (T1, T2 ) and the percentage of the maximum possible effect ( MPE ) was calculated. Lumbar segment of the spinal cord ( L4-6 ) was removed for microscopic examination and determination of c-Fos expression (by immuno-histochemistry) at 7, 24 and 48 h after IT dexmedetomidine or normal saline administration. Results PWMT, TFL and the percentage of MPE were significantly increased after IT dexmedetomidine as compared with the baseline values at T0 in groups D1-3 ( P ＜ 0.05). PWMT was significantly higher at T1 and TFL and the percentage of MPE were higher at T2 in groups D1-3 than in groups C and N,and in group D3 than in groups D1,2 ( P ＜ 0.05). At 7,24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in groups C and N( P ＜ 0.05). There was no significant difference in c-Fos expression at 48 h after IT dexmedetomidine between group D3 and groups C and N ( P ＞ 0.05 ). At 24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in other 4 groups( P ＜ 0.05). Slight spinal cord injury was observed at 24 h after IT dexmedetomidine in group D3. Conclusion IT dexmedetomidine has antinociceptive effect. High dose dexmedetomidine IT can produce transient reversible toxicity to the spinal cord.

BACKGROUND: Ischemic preconditioning (IPC) can induce endogenous protection mechanism, which effectively prevent ischemia/reperfusion injury following organ transplantation. Cold and warm ischemia may induce ischemia/reperfusion injury of pancreas transplantation, and apoptosis of pancreatic acinar cells is one of the important reasons of pancreas graft functional defect after transplantation. Mitochondrial DNA has repair system, and its balance with mitochondrial DNA injury influences disease occurrence and outcome.OBJECTIVE: To observe the effect of IPC on apoptosis of transplanted pancreatic acinar cells, and the possible role of reactive oxygen (ROS) and mitochondrial DNA repair enzyme.METHODS: A total of 50 health, male, Sprague-Dawley rats were randomly divided into three groups: sham operated (n = 10), donors (n = 20) and recipients (n = 20). The recipients were randomly divided into ischemia/reperfusion group (IR, n = 10) and IPC group (n = 10). The sham operated group was subjected to abdominal open and close operation. IR group and IPC group received establishment of diabetic model by streptozotocin injection. IR rats received whole pancreatic-duodenal transplantation alone. IPC rats received whole pancreatic-duodenal transplantation exposed ischemic preconditioning with 5 minutes ischemia and 5 minutes reperfusion twice. All grafts were keep with warm ischemia time 15 minutes and cold ischemia (in 4 ℃ UW preservation solution) time 180 minutes. Twelve hours after reperfusion, serum amylase, blood glucose, Caspase-3, -9 activity were detected. Pancreatic acinar cell apoptosis was measured by flow cytometry. Mitochondrial cross-membrane potential (Δψ) was measured by monitoring the fluorescence spectrum of rhodamine 123. Mitochondrial H2O2 generation was determined using dichlorofluorescein as a probe. 8-oxodG in mitochondrial DNA (mtDNA) was measured with HPLC system. Release of cytochrome C, phosphorylation of Akt and mitochondrial OGG1 protein expression were determined by Western-blotting. RESULTS AND CONCLUSION: The ischemia preconditioning can relieve the pancreatic acinar cell apoptosis in pancreas graft and relieve IR injury by decreasing mitochondrial oxidative stress, mtDNA injury, and increasing phosphorylation of Akt and mitochondrial OGG1 expression.

Objective To investigate the effects of different duration of sevoflurane anesthesia in the neonatal period on the long?term cognitive function and hippocampal synaptic plasticity in rats. Methods Twenty?four pathogen?free healthy Sprague?Dawley rats of both sexes, aged 7 days, weighing 12-16 g, were divided into 3 groups ( n=8 each) using a random number table: control group ( group C) , sevoflu?rane anesthesia for 2 h group ( group S1 ) , and sevoflurane anesthesia for 6 h group ( group S2 ) . Group S1 and group S2 inhaled 2% sevoflurane for 2 and 6 h, respectively. Morris water maze test was performed at 30 days after the end of anesthesia ( postnatal day 37) to assess the cognitive function. After the end of the test, the rats were sacrificed, and hippocampi were isolated for determination of the expression of brain?de?rived neurotrophic factor ( BDNF) , postsynaptic density?95 ( PSD?95) and synapsin 1 in hippocampal tis?sues by Western blot. Results Compared with group C, the escape latency on 4th and 5th days of the test in group S1 and on 2nd-5th days of the test in group S2 was significantly prolonged, and the frequency of crossing the original platform was significantly decreased, and the time of staying at the platform quadrant was significantly shortened in S1 and S2 groups, the expression of BDNF, PSD?95 and synapsin 1 in hipp?ocampal tissues was significantly down?regulated in group S2 (P<0?05), and no significant change was found in the expression of BDNF, PSD?95 and synapsin 1 in hippocampal tissues in group S1 ( P>0?05) . Compared with group S1 , no significant change was found in the escape latency and frequency of crossing
the original platform (P>0?05), the time of staying at the platform quadrant was significantly shortened, and the expression of BDNF, PSD?95 and synapsin 1 in hippocampal tissues was significantly down?regula?ted in group S2 ( P<0?05) . Conclusion Short?time and long?time sevoflurane anesthesia both can induce long?term cognitive dysfunction in the neonatal period, and the severity is aggravated with prolonged anes?thesia; the partial mechanism is related to inhibition of the synaptic plasticity of hippocampal neurons of rats.

Objective To investigate the effects of ischemic pre- and postconditioning on cerebral glycogen synthase kinase-3 beta (GSK-3β) activity in a rat model of global cerebral ischemia-reperfusion (I/R).Methods Forty male Wistar rats weighing 200-230 g were randomly allocated into 4 groups (n =10 each) : Ⅰ group sham operation (group S); Ⅱ group I/R; Ⅲ group ischemic preconditioning (group IPR) and Ⅳ group ischemic postconditioning (group IPO). The animals were anesthetized with intraperitoneal 10% chloral hydrate 0.4 ml/100 g. Global cerebral ischemia was induced by four-vessel-occlusion in group Ⅱ , Ⅲ and Ⅳ. Bilateral vertebral arteries were cauterized and bilateral carotid arteries were occluded for 10 min. In group IPR cerebral ischemia was preceded by 3 cycles of 10 s ischemia followed by 30 s reperfusion. The group IPO received 3 cycles of 30 s reperfusion followed by 10 s ischemia at the end of 10 min cerebral ischemia. The animals were killed 2 days later. The brains were immediately removed for determination of neuronal apoptosis in the cortex (by TUNEL), the infarct size (by TTC), p-GSK-3β activity (by spectrum assay) and the expression of Bcl-2, Bax and Caspase-3 (by SP). Linear correlation of p-GSK-3β activity with the number of apoptotic neurons in the cortex and cerebral infarct size was analyzed. Results Cerebral I/R significantly increased the number of apoptotic neurons in the cortex and infarct size, decreased p-GSK-3β activity, down-regulated Bcl-2 expression and up-regulated Bax and Caspase-3 expression in group I/R as compared with group S. Ischemic pre- and postconditioning significantly attenuated these cerebral I/R-induced changes. The p-GSK-3β activity was negatively correlated with the number of apoptotic neurons in the cortex and cerebral infarct size. Conclusion Ischemic pre- and postconditioning reduces cerebral I/R injury through inhibiting the activity of GSK-3β.

Objective To observe the lung protection of Astragalus membranaceus against radiotherapy to intermediate-stage and terminal thoracic neoplasm, and its influence on TNF-α and ET expression.Methods The patients with intermediate-stage and terminal thoracic neoplasm under radiotherapy were divided into a treatment group and a control group.Patients in the treatment group took 10 ml of Asragalus membranaceus twice a day.for consecutive 6 months from the beginning of radio therapy.TNF-α and ET in the plasma were measured before and after the radiotherapy.The clinical symptom,iconographic changes and lung diffusion were observed from the 15th day of radiotherapy.Results The TNF-α and ET in plasma afterthe radiotherapy were(2.48±0.75)as/ml and(69.32±23.03)pg/ml for the treatment group,and(5.12±1.01)ns/ml and(97.87±37.83)pg/ml for the control group with the statistial difference(x2=7.49,6.57,P<0.001).The decrease of CO diffusion 5 and 10 months after the radiotherapy in the treatment group was statistically different compared with that in the control group(x2=3.98,3.78,P<0.05).There was a statistical difference of the incidence of acute radiation pneumonitis and pulmonary fibrosis between these two groups(P<0.05).Conclusions Astragalus membranaceus could inhibit the excess expression of TNF-α and ET in plasma and reduce the deterioration of diffusion after radiotherapy,so that it can be used for intervention of lung injuries from radiotherapy.

Objective To evaluate the effects of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathway on the brain injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods Pathogen-free male Sprague-Dawley rats,weighing 200-220 g,were used in this study.Diabetes mellitus was induced by intraperitoneal 1％ streptozotocin 60 mg/kg and confirmed by blood glucose level ≥ 16.7 mmol/L 3 days later.Twenty-four rats with diabetes mellitus were randomly allocated into 3 groups (n =8 each) using a random number table:sham operation group (group S),I/R group,and myocardial I/R + AG490 (JAK inhibitor) group (group ⅠA).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min,followed by 120 min of reperfusion in the rats anesthetized with pentobarbital sodium.AG490 3 mg/kg was injected intravenously at 20 min before reperfusion in group IA.The rats were sacrificed at 120 min of reperfusion,and the brains were removed for determination of caspase-3 and nuclear factor kappa B (NF-κB) activities (using colorimetric method),cell apoptosis (by TUNEL),and expression of interleukin-1 (IL-1),IL-6,IL-8,Bax,Bcl-2,cytochrome C (Cyt c),phosphorylated JAK2 (p-JAK2),and phosphorylated STAT3 (p-STAT3) (by Western blot).Apoptosis index was calculated.Results Compared with group S,the expression of Bax,Cyt c,IL-1,IL-6,IL-8,p-JAK2 and p-STAT3 was significantly up-regulated,the expression of Bcl-2 was down-regulated,and NF-κB and caspase-3 activities and apoptosis index were increased in I/R and IA groups (P＜0.05).Compared with group I/R,the expression of Bax,Cyt c,IL-1,IL-6,IL-8,p-JAK2 and p-STAT3 was significantly down-regulated,the expression of Bcl-2 was up-regulated,and NF-κB and caspase-3 activities and apoptosis index were decreased in group IA (P＜0.05).Conclusion Inflammatory responses mediated by JAK2/STAT3 signaling pathway are involved in the brain injury induced by myocardial I/R in diabetic rats.

Objective To observe analgesia effect of morphine hydrochloride and hydromorphone hydrochloride in patients after transurethral resection of prostate. Methods Patients after transurethral resection of the prostate (TURP) were randomly divided into 2 groups, morphine hydrochloride group (n=45) and hydromorphone hydrochloride group (n=47). Analgesia, sedation efficacy and adverse reactions were evaluated at 6 and 24 h after they received epidural postoperative analgesia by using VAS score and Ramsay score. Results In 6 h, hydromorphone hydrochloride group had a better pain tolerance and feeling than morphine hydrochloride group (P<0.05) [(2.9±0.3) score vs.(1.3±0.2) score, (2.4±0.3) score vs. (0.9±0.2) score].However, in 6-12 h, the results were on the contrary (P<0.05) [(3.4±0.3) score vs.(5.4±0.3) score, (3.3±0.2) score vs. (5.7±0.4) score].After 24 h, there was no difference between the two groups (P>0.05).There were no differences in adverse reactions between the two groups ( P>0. 05 ) . Conclusion Hydromorphone has a better effect than morphine in epidural analgesia in 6 h.

Objective To investigatc the role of phosphatidylinositol 3-kinase (PI3K)/protein-serine-threonine kinases (Akt) signal pathway in ginsenoside Rb1 pretreatment-induced attenuation of myocardial ischemiareperfusion (I/R) injury in diabetic rats.Methods Male SD rats weighing 250-300 g were used in this study.Diabetes mellitus was induced by intraperitoneal streptozotocin and confirmed by fasting blood glucose ≥ 16.7mmol/L.Eight weeks after diabetes mellitus was induced,48 rats were randomly divided into 4 groups ( n =12each):group myocardial I/R (group I/R); group ginsenoside Rb1 (group R); group ginsenoside Rb1 + wortmannin (PI3K inhibitor) (group RW) and group wortmannin (group W).Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.Ginsenoside Rb1 40 mg/kg was injected iv at 10 min before ischemia in groups R and RW,while in groups RW and W wortmannin 15 μg/kg was injected iv at 20 min before ischemia.Arterial blood samples were collected at the end of 120 min reperfusion for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) activities.The rats were then sacrificed.The infarct size was measured by tetrazolium method.Myocardial apoptosis was detected by TUNEL and apoptotic index (the number of apoptotic myocardial cells/the total number of myocardial cells) was calculated.The expression of Akt and phosphorylated Akt (p-Akt) was determined by Western blotting.Results Ginsenoside Rb1 pretreatment significantly reduced the infarct size,myocardial cell apoptotic index and serum CK and LDH activities and up-regulated p-Akt expression in group R as compared with group I/R.The protective effects of ginsenoside Rbl against myocardial I/R injury were significantly attenuated by wortmannin pretreatment in group RW compared with group R.Conclusion PI3K/Akt signal pathway is involved in the protective effects of ginsenoside Rb1 against myocardial I/R injury in diabetic rats.

Objective To systematically review the efficacy of bispectral index (BIS) monitoring for prevention of intraoperative awareness in patients under general anesthesia.Methods The Cochrane Central Register of Controlled Trials (Central),PubMed,Medline,and EMBASE were searched for randomized controlled clinical trials involving detection of intraoperative awareness in patients in whom BIS was used or not under general anesthesia.The quality of the studies was evaluated by the method recommended by Cochrane Collaboration.Evaluation indexes included the incidence of intraoperative awareness.Meta-analysis was conducted using RevMan 5.1 software.Results Five randomized controlled clinical trials involving 34181 patients were included in this meta-analysis.There were 17432 cases in whom BIS was applied and the incidence of intraoperative awareness was 0.132％.There were 16749 cases in whom BIS was not used and the incidence of intraoperative awareness was 0.245％.There was no significant difference in the incidence of intraoperative awareness between the two groups (P ＞0.05).Further analysis was performed according to the method of anesthesia.In inhalational anesthesia,there were 13288 cases in whom BIS was applied and the incidence of intraoperative awareness was 0.128％,and there were 13202 cases in whom BIS was not applied and the incidence of intraoperative awareness was 0.113％.There was no significant difference in the incidence of intraoperative awareness between the two groups (P ＞ 0.05).In total intravenous anesthesia,there were 4144 cases in whom BIS was applied and the incidence of intraoperative awareness was 0.145％,and there were 3547 cases in whom BIS was not applied and the incidence of intraoperative awareness was 0.733 ％.The incidence of intraoperative awareness was significantly lower in the patients in whom BIS was applied than those in whom BIS was not applied (P ＜ 0.01).Conclusion BIS monitoring can effectively prevent the development of intraoperative awareness in patients under total intravenous anesthesia,but can not prevent the development of intraoperative awareness in patients under inhalational anesthesia.

Objective To evaluate the effect of dexmedetomidine on spinal purinergic receptor 2X-4 (P2X4)/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) pathway in a rat model of diabetic neuropathic pain (DNP).Methods Twenty-four pathogenfree adult male Sprague-Dawley rats,weighing 200-220 g,aged 8 weeks,were allocated into 3 groups (n =8 each) using a random number table:control group (C group),DNP group and DNP plus dexmedetomidine group (DNP+D group).Diabetes mellitus was induced by intraperitoneal 1％ streptozotocin 60 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.In group DNP+D,dexmedetomidine 50 μg/kg was intraperitoneally injected once a day for 6 consecutive weeks starting from 3 days after the model was successfully established.The mechanical paw withdrawal threshold (MWT) and sciatic nerve conduction velocity (SNCV) were measured at 2,4 and 6 weeks after injection of dexmedetomidine.The rats were sacrificed at 6 weeks after injection of dexmedetomidine,and the L4-6 segments of the spinal cord were removed for examination of the pathological changes (with a light microscope) and for determination of P2X4,NLRP3 and interleukin-lbeta (IL-1β3) expression (by Western blot).The sural nerve was obtained for examination of the ultrastructure by electron microscopy.Results Compared with group C,the MWT was significantly decreased at 2,4 and 6 weeks after injection of dexmedetomidine,the SNCV was decreased at 6 weeks after injection of dexmedetomidine,the expression of P2X4,NLRP3 and IL-1β in the spinal cord was up-regulated (P＜0.05),and the pathological changes of the spinal cord and sural nerve were marked in DNP and DNP+D groups.Compared with group DNP,the MWT was significantly increased at 2,4 and 6 weeks after injection of dexmedetomidine,the SNCV was increased at 6 weeks after injection of dexmedetomidine,the expression of P2X4,NLRP3 and IL-1β in the spinal cord was down-regulated (P＜0.05),and the pathological changes of the spinal cord and sural nerve were significantly attenuated in group DNP+D.Conclusion The mechanism by which dexmedetomidine mitigates DNP is probably related to inhibition of P2X4/NLRP3 pathway in rats.