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Objective To evaluate the effect of pulsed radiofrequency (PRF) on spinal adenosine triphosphate (ATP)-P2X4-NLRP3 signaling pathway in rats with neuropathic pain.Methods Forty healthy clean-grade adult male Sprague-Dawley rats,aged 2-3 months,weighing 220-260 g,were divided into 4 groups (n =10 each) using a random number table method:sham operation group (group S),neuropathic pain group (group NP),sham PRF group (group SPRF) and PRF group.Neuropathic pain was induced by chronic constriction injury to the left sciatic nerve of anesthetized rats.Rats received PRF treatment on 7th day after establishing the model in group PRF.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before establishing the model (T0) and at 3,7,10,14,21 and 28 days after establishing the model (T1-6).The rats were then sacrificed and the spinal cord was removed for determination of P2X4 and NLRP3 expression (by Western blot) and interleukin-1beta (IL-1β),IL-2,IL-6 and tumor necrosis factor-alpha (TNF-α) contents (by enzymelinked immunosorbent assay).Results Compared with group S,the MWT and TWL were significantly decreased at T1-6,the expression of P2X4 and NLRP3 was up-regulated,and the contents of IL-1β,IL-2,IL-6 and TNF-α were increased in NP,SPRF and PRF groups (P＜0.05).Compared with group NP and group SPRF,the MWT and MWT were significantly increased at T3-6,the expression of P2X4 and NLRP3 was down-regulated,and the contents of IL-1 β,IL-2,IL-6 and TNF-α were decreased in group PRF (P＜0.05).Conclusion The mechanism by which PRF alleviates neuropathic pain is related to inhibiting ATP-P2X4-NLRP3 signaling pathway in rats.
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Objective To evaluate the effect of penehychdine hydrochloride pretreatment on nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway during myocardial ischemia-reperfusion (Ⅰ/R) in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 2-3 months,weighing 220-240 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),myocardial Ⅰ/R group and penehyelidine hydrochloride pretreatment group (group PHC).Myocardial Ⅰ/R was induced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.At 30 min before ischemia,penehyelidine hydrochloride 2 mg/kg was injected intraperitoneally in group PHC,and the anterior descending branch of left coronary artery was only exposed but not ligated in group S.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) and expression of Nrf2,heme oxygenase-1 (HO-1),NQO1 and γ-glutamylcysteine synthetase (γ-GCS) protein and mRNA (by using Western blot or real-time fluorescence quantitative polymerase chain reaction).The percentage of myocardial infarct size and apoptosis index were calculated.Results Compared with group S,the percentage of myocardial infarct size and apoptosis index were significantly increased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was down-regulated in Ⅰ/R and PHC groups (P＜0.05).Compared with group l/R,the percentage of myocardial infarct size and apoptosis index were significantly decreased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was up-regulated in group PHC (P＜0.05).Conclusion Penehyclidine hydrochloride pretreatment attenuates myocardial Ⅰ/R injury through activating Nrf2-ARE signaling pathway in rats.
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Objective To evaluate the effect of prostaglandin E1 (PGE1) on propofol-induced neuroapoptosis in hippocampus of newborn rats.Methods Thirty-six clean-grade healthy newborn SpragueDawley rats,aged 7 days,weighing 11-16 g,were divided into 3 groups (n=12 each) using a random number table method:control group (group C),propofol group (group P) and group PGE1.Propofol 75 mg/kg was intraperitoneally injected once every other day for 7 consecutive days in P and PGE1 groups.PGE1 10 μg/kg was injected via the tail vein at 30 min before each injection of propofol in group PGE1.Normal saline 3 ml/kg was intraperitoneally injected once every other day for 7 consecutive days in group C.The rats were sacrificed at 60 min after emergence from the last injection.The hippocampi were harvested for determination of neuroapoptosis (by TUNEL),expression of caspase-3,Bcl-2 and Bax (by Western blot),and contents of intedeukin-1bota (IL-1β),IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbont assay).Results Compared with group C,the contents of hippocampal IL-1β,IL-6 and TNF-α were significantly increased,apoptosis index was increased,the expression of caspase-3 and Bax was up-regulated,and the expression of Bcl-2 was down-regulated in P and PGE1 groups (P＜0.05).Compared with group P,the contents of hippocampal IL-1β,IL-6 and TNF-α were significantly decreased,apoptosis index was decreased,the expression of caspase-3 and Bax was down-regulated,and the expression of Bcl-2 was up-regulated in group PGE1 (P＜0.05).Conclusion PGE1 can reduce propofol-induced neuroapoptosis in hippocampus of newborn rats,and the mechanism may be related to inhibiting inflammatory responses of the hippocampus.
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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 and contrast the effects of dexmedetomidine and ketamine on the restlessness and analgesia during recovery period of anesthesia after tonsillectomy in children. Methods Sixty ASA Ⅰ-Ⅱ child patients underwent tonsillectomy and adenoidectomy were randomly divided into three groups, group P (appropriate amount of placebo was given in the operation), group D (dexmedetomidine) and group K (ketamine). Data of mean arterial pressure and heart rate of three groups were documented before anesthesia (T0), during extubation (T1), 5 min (T2), 10 min (T3), 15 min (T4) and 30 min (T5) after extubation were recorded. The analepsia time, adverse reactions, restlessness score and pain score were collected in three groups of patients. Results Compared with group P, values of mean arterial pressure and heart rate were more stable at T1, T2 and T3 in groups D and K (P<0.05). The restlessness score, incidence of restlessness and adverse reactions were lower in groups D and K than those in group P (P<0.05), and which were lower in group D than those of group K (P<0.05). Conclusion Both dexmedetomidine and ketamine can play an analgesic role in recovery period of anesthesia and reduce restlessness, adverse reactions and pain score in child patients. Moreover, dexmedetomidine is more effective on inhibiting restlessness and adverse reactions.
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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 investigate the effects of surgical trauma on Toll?like receptor 4 ( TLR4) expression in the hippocampus of aged mice. Methods Ninety male Kunming mice, aged 16-18 months, weighing 30-40 g, were randomly divided into 3 groups ( n=30 each) using a random number table:control group ( group C), anesthesia group ( group A), and partial hepatectomy group ( group PH). Normal saline 0.1 ml∕10 g was injected intraperitoneally in group C. In group A, fentanyl 0.2 mg∕kg and droperidol 5 mg∕kg were injected intraperitoneally. In group PH, fentanyl 0. 2 mg∕kg and droperidol 5 mg∕kg were injected intraperitoneally, and the mice underwent partial hepatectomy. Cognitive function was assessed using Morris water maze test at 1, 3, and 7 days after anesthesia or surgery. After the end of the test, the hippocampus was immediately harvested for determination of the TLR4, tumor necrosis factor?alpha ( TNF?α) and interleukin?1 beta ( IL?1β) protein and mRNA expression by Western blot and real?time reverse transcriptase?polymerase chain reaction, respectively. Results Compared with group C, no significant changes were found in group PH in the escape latency, percentage of swimming distance in the target quadrant, and TLR4, TNF?α and IL?1β protein and mRNA expression at each time point after anesthesia in group A (P>0.05), and the escape latency was significantly prolonged, the percentage of swimming distance in the target quadrant was decreased, and the expression of TLR4, TNF?α and IL?1βprotein and mRNA was up?regulated at 1 and 3 days after surgery in group PH ( P<0. 05 or 0. 01 ) . Compared with group A, the escape latency was significantly prolonged, the percentage of swimming distance in the target quadrant was decreased, and the expression of TLR4, TNF?αand IL?1βprotein and mRNA was up?regulated at 1 and 3 days after surgery in group PH (P<0.05 or 0.01). Conclusion Surgical trauma can up?regulate the expression of TLR4 in the hippocampus of aged mice, which may be involved in the mechanism of surgical trauma?induced postoperative cognitive dysfunction.
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Objective:To analyze the direct-to-patient( DTP)model in the field of pharmacy retail. Methods:The meaning and features of the model were analyzed,the advantages and challenges of the model were summarized,and some countermeasure sugges-tions for the model application in the pharmacy retail field were provided. Results:The DTP model can promote the development of drug retail enterprises. However,there are still some challenges needing continue exploration in practice. Conclusion:In order to pro-mote the application and development of the DTP model,drug retail enterprises demand the policy adjustment by government,increased investment,enhancement of centralized development and implementation of new business forms.
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Objective To evaluate the effects of propofol on the expression of hippocampal γ-aminobutyric acid (GABAA) and NMDA receptor in a rat model of inflammatory pain (IP).Methods A total of 32 female Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups (n =8 each):control group (group C),group IP,and different doses of propofol groups (P1,2 groups).IP was induced by injection of formalin.In group C,normal saline and dimethyl sulfoxide (DMSO) 0.1 ml/kg were injected intraperitoneally.In group IP,normal saline and DMSO 0.1 ml/kg were injected intraperitoneally,and 5 min later formalin was injected.In P1,2 groups,propofol 30 and 100 mg/kg were intraperitoneally injected,respectively,and 5 min later formalin was injected.The pain behavior of rats was observed within 1 h after injection of formalin and pain intensity scoring (PIS) value was calculated.The animals were sacrificed at 1 h after injection of formalin and the hippocampi were isolated for determination of GABAA and NMDA receptor expression by immunohistochemisty.Results Compared with group C,PIS value was significantly increased,GABAA and NMDA receptor expression was up-regulated in IP and P1.2 groups.Compared with group IP,PIS value was significantly decreased,GABAA receptor expression was up-regulated,and NMDA receptor expression was down-regulated in P1,2 groups.PIS value was significantly lower,GABAA receptor expression was higher,and NMDA receptor expression was lower in group P2 than in group P1.Conclusion Intraperitoneal propofol can down-regulate NMDA receptor expression in hippocampi of rats with IP,thus inhibiting responses to pain sensitivity; intraperitoneal propofol can up-regulate hippocampal GABAA receptor expression,thus enhancing endogenous mechanism of analgesia.
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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 investigate the effect of postoperative analgesia with difference methods on immunity in patients after thoracic tumour surgery. Methods Forty ASA Ⅰ-Ⅱ patients aged 35-65 years old undergoing thoracic tumour surgery were randomized to receive either postoperative patient- controlled intravenous analgesia (PCIA) (group Ⅰ, 20 cases) or patient-controlled epidural analgesia (PCEA) (group E, 20 cases) for 48 h. Medicine compatibility in group Ⅰ: sulfentanyl 1μg/ml, tropisetron 0.05 mg/ml, the PCIA pump was set up to deliver a 5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h. Epidual catheter was placed at T4-5interspace before induction of anesthesia in group E. The PCEA solution contained 2 mg/ml ropivacaine. The PCEA pump was set up to deliver a 2 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h after a loading dose of 0.33% ropivacame 6 ml. The VAS score, Ramsay sedation score and complications were reeorded. Blood samples were taken before induction (baseline) and at 2 h and 1st, 3rd and 7th day after surgery for determination of plasma concentrations of cortisol, interleukin 2 (IL-2) and the level of natural killer (NK) cells and eytokine-induced killer (CIK) cells. Results There was no significant difference in VAS score at 2 h after operation between two groups [(1.8±0.3) scores in group Ⅰ and (1.8±0.5)scores in group E].Ramsay sedation score at Ist, 3rd and 7th day after operation in group E were significantly lower than those in group Ⅰ (P<0.05), The plasma concentration of cortisol at 2 h and Ist, 3rd, 7th day after operation in group Ewere significantly lower than those in group Ⅰ (P<0.05), the levels of IL-2, NK cells and CIK cells in group E were significantly higher than those in group Ⅰ (P<0.05). Conclusions The efficacy of postoperative PCEA in improving immunity after thoracic tumour surgery is better than that of postoperative PCIA.