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Objective To evaluate the effect of emulsified isoflurane postconditioning on mitophagy during myocardial ischemia-reperfusion (I/R) in rats.Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats,aged 4-5 months,weighing 250-300 g,were divided into 4 groups (n=12 each) using a random number table:sham operation group (group S),group I/R,fat emulsion group (group F) and emulsified isoflurane postconditioning group (group EIP).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 pentobarbital sodium-anesthetized rats.Starting from 3 min before reperfusion,8％ emulsified isoflurane 2 ml/kg was intravenously infused over 8 min in group EIP,while 30％ fat emulsion 2 ml/kg was intravenously infused over 8 min in group F.Rats were sacrificed at the end of reperfusion,and hearts were removed for measurement of the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),cell apoptosis (by TUNEL),mitochondrial membrane potential and expression of microtubule-associated protein 1 light chain 3 (LC3),Beclinl,P62,PINK1 and Parkin in cardiomyocytes (by using Western blot).Apoptosis index (AI) was calculated.Results Compared with group S,the myocardial infarct size and AI were significantly increased,the mitochondrial membrane potential was decreased,the expression of LC3,Beclinl,PINK1 and Parkin was up-regulated,and the expression of P62 was down-regulated in I/R,F and EIP groups (P＜0.05).Compared with group I/R,the myocardial infarct size and AI were significantly decreased,the mitochondrial membrane potential was increased,the expression of LC3,Beclinl,PINK1 and Parkin was down-regulated,and the expression of P62 was up-regulated in group EIP (P＜0.05).Compared with group F,the myocardial infarct size and AI were significantly decreased,the mitochondrial membrane potential was increased,the expression of LC3,Beclin1,PINK1 and Parkin was down-regulated,and the expression of P62 was up-regulated in group EIP (P＜0.05).Conclusion The mechanisin by which emulsified isoflurane postconditioning reduces myocardial I/R injury is related to inhibition of mitophagy in rats.
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OBJECTIVE:To observe the influence and safety of dexmedetomidine (DEX) on intraoperative wake-up quality of patients underwent neurosurgical surgery. METHODS:126 patients with general anesthesia in neurosurgery were enrolled and randomized equally into observation group and control group,with 63 cases in each group. Control group was given target con-trolled infusion of propofol with plasma target concentration of 3-5 μg/ml and remifentanil with target effect site concentration of 2-6 ng/ml for anesthesia induction and maintenance,and then plasma target concentration of remifentanil decreased to 0.5 ng/ml 30 min before wake-up. Observation group received target controlled infusion of propofol with plasma target concentration of 3-5 μg/ml and remifentanil with target effect site concentration of 2-6 ng/ml for anesthesia induction and maintenance,and then given DEX 0.3 μg/kg intravenously 30 min before wake-up and maintained at 0.1 μg/(kg·h). MAP,HR,SBP,SaO2,serum levels of IgA,IgM,IgG,IL-6,IL-8 and TNF-α were observed in 2 groups 2 h before operation(T1)and after extubation(T2)as well as the occurrence of ADR during wake-up. RESULTS:There was no statistical significance in HR,MAP,SBP,SaO2,IgA,IgM, IgG,IL-6,IL-8 and TNF-α levels at T1 and SaO2 levels at T2 between 2 groups(P>0.05). HR,MAP,SBP,IL-6 and TNF-α lev-els of observation group decreased significantly at T2 and lower than those of control group;IgA,IgM and IgG increased signifi-cantly and higher than those of control group,with statistical significance (P0.05). CONCLUSIONS:DEX influence intraoperative wake-up quality of patients underwent neurosurgical surgery slightly,and can reduce inflammatory reaction with less ADR.
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Objective To evaluate the role of spinal AMP-activated protein kinase (AMPK) signaling pathway in reduction of neuropathic pain (NP) by dexmedetomidine in rats.Methods One hundred twenty adult male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into 4 groups (n=30 each) using a random number table: sham operation group (group S);group NP;dexmedetomidine group (group Dex) and AMPK inhibitor group (group AI).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The right sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread in NP and Dex groups.In group Dex, dexmedetomidine 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed.In group AI, AMPK inhibitor Compound C 20 mg/kg was injected intraperitoneally at the end of operation, and the other treatments were similar to those previously described in group Dex.The equal volume of normal saline was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before operation (baseline) and 2, 8 and 14 days after operation (T0-3).Results Compared with group S, the MWT was significantly decreased, and the TWL was shortened at T1-3 in NP, Dex and AI groups (P＜0.05).Compared with group NP, the MWT was significantly increased, and the TWL was prolonged at T1-3 in group Dex (P＜0.05) , and no significant change was found in MWT and TWL in group AI (P＞0.05).Conclusion Spinal AMPK signaling pathway is involved in reduction of NP by dexmedetomidine in rats.
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Objective To evaluate the effects of dexmedetomidine on the expression of spinal matrix metalloproteinase-9 (MMP-9) in a rat model of neuropathic pain (NP).Methods Eighty-one adult male SpragueDawley rats,weighing 190-230 g,were randomly divided into 3 groups (n =27 each) using a random number table:sham operation group (group S); group NP; dexmedetomidine group (group Dex).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The right sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread in NP and Dex groups.In group Dex,dexmedetomidine 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed.The equal volume of normal saline was given instead of dexmedetomidine in S and NP groups.Paw withdrawal threshold to von Frey filament stimulation (MWT) and paw withdrawal latency to thermal stimulation (TWL) were measured at 1 day before operation (To,baseline) and 5,9 and 16 days after operation (T1-3).Nine animals were sacrificed after measurement of pain threshold at T1-3 and their lumbar segments (L4,5) of the spinal cord were removed for detection of MMP-9 expression (by immuno-histochemistry) and tumor necrosis factor-alpha (TNF-α) content (by ELISA).Results Compared with group S,MWT was significantly decreased,TWL was shortened,and the levels of MMP-9 and TNF-α were increased at T1-3 in NP and Dex groups.Compared with NP group,MWT was significantly increased,TWL was prolonged,and the levels of MMP-9 and TNF-α were decreased at T1-3 in Dex group.Conclusion Dexmedetomidine can inhibit up-regulation of MMP-9 expression,and decrease inflammatory responses,thus attenuating NP in rats.
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Objective To evaluate the effect of isoflurane preconditioning on inflammatory responses during spinal cord injury (SCI ) in rats .Methods Sixty adult male Sprague-Dawley rats ,weighing 250-300 g , were randomly divided into 3 groups ( n= 20 each ) using a random number table :sham operation group (S group) , SCI group , and isoflurane preconditioning group (I group ) . The animals were anesthetized with intraperitoneal pentobarbital sodium 40 mg/kg .SCI was produced by a weight-drop contusion at the T10 level .The rats inhaled 2% isoflurane for 2 h ,and the model was established at 24 h after the end of isoflurane inhalation in I group . Neurological function was assessed and scored by using the the Basso , Beattie , Bresnahan (BBB ) Locomotor Rating Scale on 7 days after SCI .Five rats in each group were then chosen and spinal cord specimens were obtained and cut into sections which were stained with haematoxylin and eosin for determination of the viable neuron count .Fifteen rats in each group were sacrificed and the spinal cord was removed for detection of nuclear factor kappaB (NF-κB ) and interleukin-1β (IL-1β) expression (by Western blot ) .Results Compared with S group ,BBB score and the number of viable neurons were significantly decreased ,and the expression of NF-κB and IL-1βprotein was up-regulated in SCI group ( P<0.05) .Compared with SCI group ,BBB score and the number of viable neurons were significantly increased ,and the expression of NF-κB and IL-1βprotein was down-regulated in group I ( P<0.05 ) .Conclusion The mechanism by which isoflurane preconditioning protects the spinal cord is related to inhibition of inflammatory responses in rats .
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Objective To evaluate the role of glycogen synthase kinase-3 beta (GSK-3β) in spinal cord ischemia/reperfusion (I/R) injury in rats.Methods Forty-eight male Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were randomly divided into 3 groups (n =16 each) using a random number table:sham operation group (group S),group I/R and I/R+ GSK-3β inhibitor LiCl group (group LiCl).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 300 mg/kg.Spinal cord ischemia was induced by 45 min occlusion of the abdominal aorta followed by reperfusion.In I/R and LiCl groups,normal saline 5 ml and LiCl 15 mg/kg were injected,respectively,via the caudal vein at 30 min before ischemia.The animals were sacrificed at 48 h of reperfusion and the lumbar segment (L4-6) of spinal cords was removed for microscopic examination and for determination of neuronal apoptosis in the anterior horn of the spinal cord (by TUNEL),and the expression of interleukin-6 (IL-6),IL-8 and IL-10 was detected (by immunohistochemistry).The apoptosis rate was calculated.Results Compared with group S,the apoptosis rate was significantly increased,IL-6 and IL-8 expression was upregulated,and IL-10 expression was down-regulated in I/R and LiCl groups.Compared with group I/R,the apoptosis rate was significantly decreased,IL-6 and IL-8 expression was down-regulated,IL-10 expression was up regulated,and the pathological damage was attenuated in LiCl group.Conclusion Activated GSK-3β is involved in the development of spinal cord I/R injury possibly by promoting synthesis and release of inflammatory factors in rats.