Effects of autophagy activation on the apoptosis of GABA neurons in the dorsal horn of postherpetic neu-ralgia model mice / 临床麻醉学杂志

Objective To investigate the effects of different degrees of autophagy on the apop-tosis of GABAergic neurons in spinal dorsal horn of postherpetic neuralgia model mice. Methods Forty-eight Kunming mice,approximately 6-8 weeks of age and weighing 18-22 g,were randomly divided into four groups by a random digital generator of SPSS 19.0:resinotoxin+autoph-agy induction group (group PHN+Rapa),resinotoxin group (group PHN),resinotoxin+autophagy inhibitor group (group PHN+3-MA)and blank control group (group C),12 mice in each group. Group C was given no treatment,and the other groups were given intraperitoneal injection of 0.2 μg/g resiniferatoxin (RTX)to prepare PHN model.After successful model establishment,group PHN+Rapa was given Rapamycin (1 μg·kg-1·d-1),physiological saline was given to group PHN, group PHN+3-MA was given 2 μg·kg-1·d-1autophagy inhibitor 3-MA.The intraperitoneal injection was continued for 14 day.The mechanical withdrawal threshold (MWT)and the latent period of thermal withdrawal latency (TWL)were detected and the mice were killed after stability. The segments of L4-6spinal cord were extracted and the relative expressions of bcl-2,Bax and autoph-agy-associated protein LC3 were detected by western blot.Detection of the number of apoptotic cells in the spinal cord by fluorescence Tunel.The number of GABA intermediate neurons in the dorsal horn of the spinal cord was labeled by immunofluorescence.Results Compared with group C,the rel-ative expression level of Bax protein increased significantly,the LC3-II/I ratio and the number of ap-optotic cells increased significantly,the relative expression level of Bcl-2 protein and the number of GABA neurons in spinal dorsal horn were significantly reduced in other groups (P<0.05).Compared with group PHN,the LC3-II/I ratio and the relative expression level of Bax protein,the number of apoptotic cells increased significantly,the relative expression level of Bcl-2 protein and the number of GABA neurons in the spinal dorsal horn were significantly decreased of group PHN+Rapa (P<0.05).Compared with group PHN,the relative expression level of LC3-II/I ratio and Bax protein, the number of apoptotic cells decreased significantly,the relative expression level of Bcl-2 protein and the number of GABA neurons in spinal dorsal horn increased significantly of group PHN+3-MA,(P<0.05).Conclusion Over activation of autophagy may be one of the mechanisms leading to the ap-optosis of GABA neurons in the dorsal horn of the spinal cord in postherpetic neuralgia.

Role of autophagy in spinal cord in maintenance of post-herpetic neuralgia in mice / 中华麻醉学杂志

Objective To evaluate the role of autophagy in the spinal cord in the maintenance of postherpetic neuralgia (PHN) in mice.Methods Forty-eight SPF Kunming mice,aged 6-8 weeks,weighing 18-22 g,were divided into 4 groups (n=12 each) using a random number table:normal control group (group C),group PHN,PHN plus autophagy inducer rapamycin group (group PHN+R) and PHN plus autophagy inhibitor 3-methyladenine (3-MA) group (group PHN+3-MA).PHN model was established by intraperitoneal injection of resiniferotoxin 0.2 μg/g.In PHN+R and PHN+3-MA groups,rapamycin 1 μg/g and 3-MA 2 μg/g were intraperitoneally injected once a day for 14 consecutive days starting from 7 days after resiniferotoxin injection.The equal volume of normal saline was given instead in group PHN.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured on 1st,3rd,6th,9th,12th and 14th days of administration of autophagy regulator (before administration).The animals were sacrificed after the last measurement of pain threshold,and the spinal cord was removed for examination of the ultrastructure and for determination of the expression of microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ),LC3 Ⅰ,Beclin-1 and P62 by Western blot.The ratio of LC3 Ⅱ to LC3 Ⅰ expression (LC3 Ⅱ /Ⅰ) was calculated.Results Compared with group C,the MWT was significantly decreased,TWL was prolonged,LC3 Ⅱ/Ⅰ was increased,Beelin-1 expression was up-regulated,P62 expression was down-regulated (P＜0.05),and the number of autophagosomes was increased under electron microscope in group PHN.Compared with group PHN,the MWT was significantly decreased,TWL,was prolonged,LC3 Ⅱ/Ⅰ was increased,Beclin-1 expression was up-regulated,P62 expression was down-regulated (P＜0.05),and the number of autophagosomes was increased under electron microscope in group PHN+R,and the MWT was significantly increased,TWL was shortened,LC3 Ⅱ/Ⅰ was decreased,Beclin-1 expression was down-regulated,P62 expression was up-regulated (P＜0.05),and the number of autophagosomes was decreased under electron microscope in group PHN+3-MA.Conclusion The maintenance mechanism of PHN may be related to the excessive activation of autophagy in the spinal cord of mice.

Effect of oxycodone in the patient controlled intravenous analgesia after laparoscopic surgery / 临床麻醉学杂志

Objective To observe the effects of PCIA with oxycodone after laparoscopic surger-y.Methods Forty ASA Ⅰ or Ⅱ patients aged 20-60 years undergoing laparoscopic surgery were as-signed to two groups randomly (n=20 per group):oxycodone group (group A)and fentanyl group (group B).Patients in group A received oxycodone (0.03 mg/kg)and patients in group B received fentanyl (2 μg/kg)at the end of surgery.The PCIA pump was turned on when the patients entered the PACU.The PCIA pump was set up with a 4 ml bolus dose,a 1 5 min lockout interval and a back-ground infusion at the rate of 2 ml/h.Numerical rating scale (NRS)was assessed for the patients in moving,in rest and visceral pain at 3,6,12,24 and 48 h after administration,and the adverse reactions were recorded.Results NRS scores of the rest and visceral pain were significantly lower in group A than in group B at each time point(P <0.05).NRS score of the movement were significantly lower in group A than in group B at 3,6 and 12 h after surgery (P <0.05).There was no significant difference in the incidences of nausea,vomiting,dizziness and respiratory depression between the two groups. Conclusion PCIA with oxycodone can safely and effectively inhibit pain after laparoscopic surgery. The effect of oxycodone for controlling the visceral pain was better than that of fentanyl.

Effect of parecoxib on postoperative hyperalgesia induced by remifentanil-based anesthesia / 中华麻醉学杂志

Objective To investigate the effect of parecoxib on postoperative hyperalgesia induced by remifentanil-based anesthesia.Methods One hundred ASA Ⅰ or Ⅱ patients,aged 21-64 yr,weighing 50-80 kg,undergoing elective laparoscopic operation,were randomly divided into 5 groups ( n =20 each):parecoxib group (group P),small dose remifentanil group (group S),large dose remifentanil group (group L),small dose remifentanil + parecoxib group (group SP) and large dose remifentanil + parecoxib group (group LP).Parecoxib 40 mg was injected intravenously at 30 min before anesthesia in groups P,SP and LP.Anesthesia was induced with midazolam0.05 mg/kg,etomidate 0.2 mg/kg,cisatracurium 0.15 mg/kg and remifentanil 1 μg/kg (fentanyl 4 μg/kg in group P).The patients was tracheal intubated and mechanically ventilated.PETCO2 was maintained at 35-45 mm Hg.Anesthesia was maintained with infusion of remifentanil at 0.05 μg·kg-1 ·min-1 (in groups S and SP) or at 0.3 μg· kg- 1· min- 1 (in groups L and LP) combined with inhalation of sevoflurane and infusion of cisatracurium at 0.12 mg·kg-1·h-1.At 30 min after operation,numeric rating scale (NRS) was used to assess the degree of pain at rest and during activity.Tramadol 1.5 mg/kg was injected intravenously after operation if needed.NRS scores were maintained ≤5.The use of tramadol and adverse effects during 24 h after operation were recorded.Results Compared with group P,NRS scores at rest and during activity were significantly increased at 30 min after operation in groups S and L,the incidence of shivering and the number of patients who needed tramadol were significantly increased in group L,and no change was found in NPS scores at rest and during activity at 30 min after operation,the incidence of adverse effects and the number of patients who needed tramadol in groups SP and LP.Compared with group S,NRS scores at rest and during activity at 30 min after operation,the incidence of shivering and the number of patients who needed tramadol were significantly increased in group L,NRS scores at rest and during activity at 30 min after operation were significantly decreased and no change was found in the incidence of adverse effects and the number of patients who needed tramadol in group SP.Compared with group L,NRS scores at rest and during activity at 30 min after operation,the incidence of shivering and the number of patients who needed tramadol were significantly decreased in group LP.Conclusion Intravenous injection of parecoxib 40 mg at 30 min before anesthesia can attenuate postoperative hyperalgesia induced by remifentanil-based anesthesia.

Proper dosage of fentanyl for open heart surgery performed under CPB without cardioplegia / 中华麻醉学杂志

Objective To determine the proper dosage of fentanyl for open heart surgery performed under cardiopulmonary bypass (CPB) without aortic cross-clamping and cardioplegia.Methods Twenty-seven ASA Ⅰ -H patients (10 male, 17 female) with fairly good cardiac function (NYHA Ⅰ - Ⅱ) scheduled for surgical repair of atrioseptal defect ( ASD) or ventricular septal defect (VSD) or mitral valve replacement (MVR) were studied. Age ranged from 18 to 44 years and body weight from 35 to 58 kg. The patients were randomly divided into three fentanyl dosage groups: group Ⅰ 10?kg ; group II 30 ?g kg-1 and group Ⅲ 50 ?g kg-1. Premedication consisted of intramuscular pethidine 1-2 mg kg-1 and scopolamine 0.05-0.06 mg kg-1 . Anesthesia was induced with midazolam 0.2 mg kg-1 and fentanyl 5 ?g kg-1 . Tracheal intubation was facilitated with vecuronium 0.15 mg g-1 . The patients were mechanically ventilated (Vr 8-10 ml kg-1 ,F 10-12 bpm,FiO2 100% ). The rest of the total dose of fentanyl (5 ?g kg-1 in group I , 25 ?g kg-1 in group II , 45 ?g kg-1 in group III) was infused after induction of anesthesia until the initiation of CPB, supplemented with inhalation of 0.6 % isoflurane. During CPB propofol was infused at 5 mg kg-1 h-1 . after discontinuation of CPB, again 0.6% isoflurane was inhaled until the end of surgery. Vecuronium 0.05 mg kg was given every 25-30 min during operation. EGG, HR, BP, CVP, SpO2, PET CO2 and body temperature (naso-pharyngeal and rectal) were continuously monitored during operation. Arterial blood samples were obtained before anesthesia (T0), 5 min after tracheal intubation (T, ) , immediately after thoracotomy (T2) , immediately before CPB (T3), 15 min after CPB was initiated (T4) , 10 min after termination of CPB (T5) and 5 min after chest was closed (T6) for blood gas analyses and determination of blood electrolytes and acid-base balance and blood concentrations of glucose, ACTH, angiotensin Ⅱ (A- Ⅱ ) and cortisol. Time of emergence from anesthesia and extubation were recorded.Results The demographic data, including age and body weight, CPB time and duration of surgery were comparable among the three groups. There were no significant changes in SpO2 , PETCO2 , body temperature, blood gases and electrolytes during operation in the three groups. MAP decreased significantly during CPB. The blood glucose, ACTH, A- Ⅱ and cortisol concentrations increased significantly during and after CPB as compared with the preanesthetic baseline (T0 ) ( P