To investigate the effect of multiple propofol anesthesia and operative trauma on neuroinflammation and cognitive function in development rats and its mechanism. A total of 104 13-day-old neonatal Sprague-Dawley rats were randomly divided into 4 groups with 26 rats in each group: control group was treated with saline q.d for propofol group was treated with propofol q.d for surgery group received abdominal surgery under local anesthesia and then treated with saline q.d for surgery with propofol group received propofol anesthesia plus abdominal surgery under local anesthesia with ropivacaine at d1, then treated with propofol q.d for At d2 of experiment, 13 rats from each group were sacrificed and brain tissue samples were taken, the concentration of TNF-α in hippocampus was detected with ELISA, the expression of caspase-3 and c-fos in hippocampal tissue was determined with immunohistochemical method, the number of apoptotic neurons in hippocampus was examined with TUNEL assay. Morris water maze test was used to examine the cognitive function of the rest rats at the age of 60 d, and the TNF-α concentration, caspase-3, c-fos expressions and the number of apoptotic neurons in hippocampus were also detected. Compared with control group, TNF-α concentration, caspase-3, c-fos expression and the neuroapoptosis in hippocampus increased significantly in other three groups (all <0.05). Compared with surgery group, propofol group and surgery with propofol group showed increased TNF-α level, caspase-3 and c-fos expressions and apoptotic cell numbers (all <0.05), but there was no significant difference between last two groups (all >0.05). Morris water maze test showed that there were no significant differences in swimming speed, escape latency, target quadrant residence time and crossing times among groups (all >0.05). TNF-α level, expressions of caspase-3 and c-fos and apoptotic cell numbers in hippocampus had no significant differences among the 4 adult rats groups (all >0.05). Abdominal surgery and multiple propofol treatment can induce neuroinflammation and neuroapoptosis in hippocampus of neonatal rats, however, which may not cause adverse effects on neurodevelopment and cognitive function when they grown up.
Anesthesia ; Animals ; Cognition ; Hippocampus ; Propofol/adverse effects* ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the maximum dose of continuous mivacurium infusion for intraoperative neuromonitoring (IONM) and observe the adverse reactions during thyroid surgery under total intravenous anesthesia (TIVA). METHODS: Thirty patients undergoing IONM during thyroid surgery received continuous infusion of mivacurium at the initial rate of 14.97 μg · kg RESULTS: The EC CONCLUSIONS In patients undergoing thyroid surgery under TIVA, the EC
Anesthesia, Intravenous ; Humans ; Mivacurium ; Propofol ; Remifentanil ; Thyroid Gland

OBJECTIVE: To determine the maximum dose of continuously infused mivacurium for intraoperative neuromonitoring and observe its adverse effects in thyroid surgery. METHODS: Twenty-eight patients undergoing thyroid surgery with intraoperative neuromonitoring received continuous infusion of mivacurium at the initial rate of 5.43 μg?kg?min, and the infusion rate for the next patient was adjusted based on the response of the previous patient according to the results of neurological monitoring. The depth of anesthesia was maintained with sevoflurane and remifentanil during the surgery. The LD50 and 95% of mivacurium were calculated using Brownlee's up-and-down sequential method. RESULTS: The LD50 of continuously infused mivacurium was 8.94 μg?kg?min (95% : 8.89- 8.99 μg?kg?min) during thyroid surgery, which did not affect neurological function monitoring. Transient chest skin redness occurred after induction in 9 patients (32.1%). None of the patients experienced intubation difficulties or showed intraoperative body motions during the surgery. CONCLUSIONS In patients undergoing thyroid surgery under anesthesia maintained by inhalation and intravenous infusion, the LD50 of mivacurium was 8.94 μg?kg?min (95% : 8.89-8.99 μg?kg?min) for continuous infusion, which does not cause serious adverse effects during the operation.
Anesthesia ; Anesthetics, Inhalation ; Anesthetics, Intravenous ; Humans ; Intraoperative Neurophysiological Monitoring ; methods ; Lethal Dose 50 ; Mivacurium ; administration & dosage ; adverse effects ; Neuromuscular Nondepolarizing Agents ; administration & dosage ; adverse effects ; Remifentanil ; Sevoflurane ; Thyroid Gland ; surgery

Objective To investigate the protective effects of dexmedetomidine (Dex) against glutamate-induced cytotoxicity in PC12 cells and its mechanism.Methods PC12 cells were treated with varying concentrations of dexmedetomidine 1 h before exposure to a high concentration of glutamate.The cell viability was measured by MTT assay,and LDH release,MDA content and SOD activity were measured.The level of ROS was tested by DCFH-DA staining and flow cytometry.The level of intracellular Ca2+ was detected by Fluo-8 staining and flow cytometry,and the mitochondrial membrane potential (MMP) was determined with JC-1 staining and flow cytometry.Results Within the concentration range of 0.01 to 100 μrnol/L,Dex dose-dependently protected PC12 cells against glutamate-induced cytotoxicity.Treatment with 100 μmol/L Dex significantly increased the cell viability to (86.6±2.2)％ of that of the control cells (P＜0.01) and decreased LDH release to 1.4±0.1 folds of the control level (P＜0.01).In PC12 cells exposed to glutamate,Dex pretreatment significantly reduced MDA content (P＜0.01),enhanced SOD activity (P＜0.01),inhibited ROS overproduction (P＜0.01),reduced intracellular Ca2 + level (P＜0.01) and maintained a stable MMP (P＜0.01).Conclusion Dexmedetomidine can protect PC12 cells against glutamate-induced injury possibly in relation with its anti-oxidative activity,inhibitory effect on intracellular calcium overload and protective effect of the mitochondria.

Objective To investigate the protective effects of dexmedetomidine (Dex) against glutamate-induced cytotoxicity in PC12 cells and its mechanism.Methods PC12 cells were treated with varying concentrations of dexmedetomidine 1 h before exposure to a high concentration of glutamate.The cell viability was measured by MTT assay,and LDH release,MDA content and SOD activity were measured.The level of ROS was tested by DCFH-DA staining and flow cytometry.The level of intracellular Ca2+ was detected by Fluo-8 staining and flow cytometry,and the mitochondrial membrane potential (MMP) was determined with JC-1 staining and flow cytometry.Results Within the concentration range of 0.01 to 100 μrnol/L,Dex dose-dependently protected PC12 cells against glutamate-induced cytotoxicity.Treatment with 100 μmol/L Dex significantly increased the cell viability to (86.6±2.2)％ of that of the control cells (P＜0.01) and decreased LDH release to 1.4±0.1 folds of the control level (P＜0.01).In PC12 cells exposed to glutamate,Dex pretreatment significantly reduced MDA content (P＜0.01),enhanced SOD activity (P＜0.01),inhibited ROS overproduction (P＜0.01),reduced intracellular Ca2 + level (P＜0.01) and maintained a stable MMP (P＜0.01).Conclusion Dexmedetomidine can protect PC12 cells against glutamate-induced injury possibly in relation with its anti-oxidative activity,inhibitory effect on intracellular calcium overload and protective effect of the mitochondria.

OBJECTIVETo explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice.

METHODSForty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded.

RESULTSCompared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01); anesthesia duration was shorter on day 3 than on day 2 in P50 + Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern.

CONCLUSIONVitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.

Anesthesia ; Anesthesia Recovery Period ; Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Ascorbic Acid ; administration & dosage ; pharmacology ; Drug Tolerance ; Mice ; Propofol ; administration & dosage ; pharmacology

Objective To observe the effect of dexmedetomidine on inflammation, oxidative stress and lung injury in lipopolysaccharide( LPS)-induced septic mice.Methods Forty eight male adult BALB/c mice were randomly divided into three groups (n=16): normal control group (Ctrl), sepsis group (Sep), and Dex group.Ae septic mice model was established by LPS 20 mg/kg,and Dex 30μg/kg injected intraperitoneally at 0.5 h after LPS injection.The concentrations of serum IL-6 and IL-10 were detected at 2 h and 6 h after LPS injection while myeloperoxidase ( MPO ) activity and malondialdehyde( MDA) content of lungs were detected and weight dry ratio ( W/D) of lungs was calculated at 6 h after LPS injection.Pathological changes were observed in left lung HE stained with optical microscopy at 6 h after LPS injection. Results Compared with Sep group, the concentrations of serum IL-6 decreased significantly(P <0.05), while the concentrations of IL-10 increased significantly(P<0.05) at 2 h and 6 h after LPS injection in Dex group.MPO activity, MDA content and W/D of lungs decreased significantly(P<0.05) at 6 h after LPS injection in Dex group.The injury to the lung was lightened significantly under optical microscopy in Dex group.Conclusion Dex protects against LPS-induced ALI in septic mice by inhibiting systemic inflammatory response, reducing lung tissue inflammatory infiltration and oxidative stress.

Objective To observe the effects of propofol and etomidate on inflammation and ox-idative stress in septic mice.Methods Sixty-four male adult BALB/c mice were randomly divided into four groups:normal control group (N),sepsis group (S),propofol treatment group (P)and etomid-ate treatment group (E).The septic mice model was established by lipopolysaccharide (LPS,20 mg/kg)intraperitoneal injection,and propofol (60 mg/kg)or etomidate (10 mg/kg)was injected in the abdominal cavity at 0.5 h after LPS injection.Serum interleukin-6 (IL-6)concentrations and in-terleukin-10 (IL-10)concentrations were measured at 2 h and 6 h after LPS injection;malondialde-hyde (MDA)content of lung,liver and kidney tissue was measured at 6 h after LPS injection. Results Compared with group N,serum IL-6 concentrations increased significantly (P <0.05),and IL-10 concentrations decreased significantly (P <0.05)at 2 h and 6 h after LPS injection in group S;MDA content of lung,liver,kidney increased significantly (P <0.05 )at 6 h after LPS injection in group S;Compared with group S,serum IL-6 concentrations decreased significantly (P <0.05),and IL-10 concentrations increased significantly (P < 0.05 )at 2 h and 6 h after LPS injection in both group P and E;MDA content of lung,liver,kidney decreased significantly (P <0.05 )at 6 h after LPS injection in group E,but only MDA content of lung decreased significantly (P <0.05)at 6 h af-ter LPS injection in group P;Compared with group P,serum IL-6 concentrations was significantly lower (P <0.05),and IL-10 concentrations was significantly higher (P <0.05)at 2 h and 6 h after LPS injection in group E;MDA content of lung,liver,kidney was significantly lower (P <0.05)at 6 h after LPS injection in group E.Conclusion Both propofol and etomidate injected in the abdominal cavity can reduce injury of inflammatory and oxidative stress in septic mice induced by LPS,and the effect of etomidate is more significant.

Objective To explore the effect of repeated hypoxic preconditioning (RHP) on renal ischemia-reperfusion-induced hepatic dysfunction in rats and the underlying mechanism. Methods A total of 120 normal SD rats were randomly divided into 4 groups (n=40), namely RHP surgical group, RHP sham-operated (RHPS) group, nonhypoxic surgical group (IRI group), and nonhypoxic sham-operated group (S group). The rats in the hypoxic groups were exposed to hypoxia in a hypoxic chamber for 5 days prior to establishment of renal ischemia-reperfusion model by resection of the right kidney and clamping the left renal hilum. Serum alanine aminotransferase (ALT), IL-17A, TNF-α, liver superoxide dismutase (SOD) and nitric oxide (NO) were detected at 2, 8 and 24h after reperfusion, and Western blotting was used to determine the expression of p-PI3K and p-AKT;HE staining was used to observe the structural changes in the liver. Results Compared with IRI group, RHP group showed significantly milder hepatic damage, lower ALT levels and higher NO levels at 2, 8, and 24 after reperfusion (P<0.05);TNF-αlevels were lowered at 24 h (P<0.05) and SOD increased at 8 h after the reperfusion (P<0.05). Compared with S group, IRI group and RHP group showed significantly higher IL-17A levels (P<0.05) but without significant difference between the latter two groups (P>0.05). The expressions of p-PI3K and P-Akt in RHP group were significantly higher than those in IRI group (P<0.05), especially at 8 h after reperfusion (P<0.05). Conclusion Repeated hypoxic preconditioning can attenuate hepatic injury induced by renal ischemia-reperfusion injury in rats.

Objective To explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice. Methods Forty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded. Results Compared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01);anesthesia duration was shorter on day 3 than on day 2 in P50+Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern. Conclusions Vitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.