1.Analgesic effcacy and spinal neurotoxicity of intrathecal different doses of dexmedetomidine in rats
Jiabao HOU ; Xingpeng XIAO ; Zhongyuan XIA ; Bo ZHAO ; Yang WU
Chinese Journal of Anesthesiology 2011;31(6):710-713
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.
2.Effects of different duration of sevoflurane anesthesia in neonatal period on long-term cognitive func-tion and hippocampal synaptic plasticity in rats
Xuelian PAN ; Bo ZHAO ; Yun XIAO ; Jiabao HOU ; Zhongyuan XIA
Chinese Journal of Anesthesiology 2016;36(9):1085-1088
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.
3.Preventive Effect of Caffeine on Alzheimer's Disease
Qianqian HOU ; Xuejiao CAO ; Jiabao WANG ; Wenjing GUO ; Xudong HOU ; Cuili ZHANG
Progress in Modern Biomedicine 2017;17(23):4452-4455,4571
Objective:To explore the effects of caffeine on the prevention of Alzheimer's disease (AD).Methods:Use Ethanol as a solvent to extract the caffeine in tea and then injecting 5% D-galactose saline solution 1ml/d/kg to establish aging model mice.Divide mice randomly into experimental group (high-dose/low-dosecaffeine),positive control group,negative control group,and normal con-trol group (NS) and injecting appropriate drugs for consecutive four weeks.Test superoxyde dismutase (SOD) and malondialdehvde (MDA) periodically.Take mice's hippocampus and use Western blotting to detect the expression of brain derived neurotrophic factor (BDNF) and extracellular signal-regulated kinasesl/2 (p-ERK1/2).Results:The expression of BDNF and p-ERK1/2,negative control group is less than low-dose experimental group and positive control group (P<0.01);The p-ERK1/2 expression of injecting D-galactose mice was significantly lower than normal group,negative control group compared weth the normal group,the differencd was significant (P<0.05).The level of SOD in model group was significantly lower than that in normal control group,high,low dose caffeine group and positive control group (P<0.01),but the level of MDA is opposite.Conclusions:Caffeine can delay aging process by increasing the level of SOD in aging mice,and enhancing the expression of BDNF and P-ERK1/2.Caffeine does a lot to prevent AD.
4.Effects of ischemic pre- and postconditioning on cerebral glycogen synthase kinase-3 beta activity in a rat model of cerebral ischemia-reperfusion
Bo ZHAO ; Zhongyuan XIA ; Wenwei GAO ; Jiabao HOU ; Yang WU ; Hong GAO ; Changjian WU
Chinese Journal of Anesthesiology 2010;30(11):1391-1393
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.
5.Effect of ischemic postconditioning on the expression of heme oxygenase-1 in acute lung ischemia-reperfusion injury in rats
Ying JIANG ; Zhongyuan XIA ; Jin GAO ; Jinjin XU ; Qingtao MENG ; Jiabao HOU
Chinese Journal of Emergency Medicine 2012;21(10):1122-1126
Objective To investigate the effect of ischemic post-conditioning (IPO) on the level of Heme oxygenase-1 (HO-1) in acute ischemia - reperfusion (I/R) injury of lung in order to illuminate its protective mechanism.Methods Forty-eight adult SD rats were randomly divided (random number) into 6groups ( n =8 each):sham operation group ( S group) ; I/R group in which the hilum of left lung was clamped for 45 min followed by 105 min reperfusion; IPO group in which left lung hilum was clamped for 45min and post - conditioned by alternation of 30 s reperfusion with 30 s re-occlusion for three times before perfect perfusion for 102 min; Hemin (HM) + I/R group; ZnPPⅨ (zinc protoporphyrin Ⅸ) + IPO group and HM + S group.Arterial partial pressure of oxygen ( PaO2 ) and malondialdehyde (MDA) content in blood serum were assayed.The left lung was removed for determination of wet/dry (W/D) lung weight ratio and level of HO-1 protein was detected by immunohistochemical technique and pathohistological changes were observed under light microscopic examination. Comparisons among multiple groups were studied by using one-way analysis of variance (ANOVA). Statistical comparisons within groups were analyzed by using paired t -test.Results The level of HO-1 in lung tissue was significantly increased in the I/R group compared with the S group and the HM + S group (P <0.01,P <0.05).Compared to the I/R group,the IPO and the HM + I/R groups had significant higher level of HO-1 ( P < 0.05,P < 0.01 ).The PaO2 was significantly lower in all experimental groups than that in the S group (90 ± 11 ) mmHg.However,the values of PaO2 in the IPO and the HM + I/R groups were higher than that in the I/R group (P < 0.01 ).In addition to severe lung tissue damage evidenced by pathohistological changes,the lung wet/dry (W/D) weight ratio and MDA level in blood serum were significantly higher in the I/R group than those in the S group (P <0.01 ),whereas the lung damage was attenuated either by IPO or by HM pretreatment (P < 0.05,IPO or HM + I/R vs.I/R).Conclusions IPO can attenuate the lung ischemia - reperfusion injury through upregulating the level of HO-1 protein and inhibiting lipid peroxidation injury.
6.Role of PI3K/Akt signal pathway in gensenoside Rb1 pretreatment-induced attenuation of myocardial ischemia-reperfusion injury in diabetic rats
Yang WU ; Zhongyuan XIA ; Bo ZHAO ; Jiabao HOU ; Qingtao MENG ; Huimin LIU
Chinese Journal of Anesthesiology 2012;32(3):358-360
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.
7.Efficacy of bispectral index monitoring for prevention of intraoperative awareness in patients under general anesthesia: a meta-analysis
Wenwei GAO ; Zhongyuan XIA ; Bo ZHAO ; Min LIU ; Jiabao HOU ; Tao LUO
Chinese Journal of Anesthesiology 2013;33(6):691-693
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.
8.Comparison of Epidural Analgesia Effect Between Morphine and Hydromorphone for Patients after Electrotomy of Prostate
Leyun ZHAN ; Zhongyuan XIA ; Lei ZHANG ; Bo ZHAO ; Yang WU ; Jiabao HOU
Herald of Medicine 2016;35(8):858-860
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.
9.Role of JAK2/STAT3 signaling pathway in brain injury induced by myocardial ischemia-reperfusion in diabetic rats
Bo ZHAO ; Yan LENG ; Xiaojing WU ; Jiabao HOU ; Yang WU ; Zhongyuan XIA
Chinese Journal of Anesthesiology 2016;36(2):211-213
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.
10.Effect of dexmedetomidine on spinal P2X4/NLRP3 pathway in a rat model of diabetic neuropathic pain
Kang LIU ; Zhongyuan XIA ; Bo ZHAO ; Fang ZHOU ; Yun XIAO ; Jiabao HOU
Chinese Journal of Anesthesiology 2017;37(5):536-539
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.