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OBJECTIVE@#To investigate the effect of escin in relieving chemotherapy-induced peripheral neuropathic pain in rats and explore and the underlying mechanism.@*METHODS@#Eighteen SD rats were randomly divided into 3 groups (@*RESULTS@#The rats in both the escin preconditioning group and escin postconditioning group showed obviously increased thresholds of mechanical allodynia and thermal hyperalgesia as compared with those in the control group (@*CONCLUSIONS@#Escin can alleviate chemotherapy-induced peripheral neuropathic pain in rats possibly by upregulating the expressions of autophagy-related proteins in the spinal cord.
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Animals , Mice , Rats , Antineoplastic Agents/therapeutic use , Autophagy , Escin/therapeutic use , Hyperalgesia/drug therapy , Neuralgia/drug therapy , Rats, Sprague-Dawley , Spinal CordABSTRACT
[Objective]This study was conducted to examine the effects of dexmedetomidine on the proliferation and angiogenesis of MHCC97H and SMCC7721 human hepatocellular carcinoma(HCC)cell lines cultured in hypoxia condition in vitro,and investigated the possible mechanism involved.[Methods]MHCC97H and SMCC7721 human HCC cell lines under hypoxia culture condition were treated with presence or absence of dexmedetomidine(100 μmol/L). Cell viability,colony formation,vasculogenic mimicry(VM) formation were assessed. The effects of dexmedetomidine on α-2A adrenergic receptor(α2A),hypoxia induced factor-1a(HIF-1a),and vascular endothelial growth factor(VEGF)protein expression were evaluated with Western blot analysis.[Results]Cell proliferation assay and colony formation assay indicated that hypoxia obviously promoted the proliferation of MHCC 97H and SMCC7721 cells(CoCl2 group vs corresponding control group,the proliferation rate of MHCC97H and SMCC7721:Day 3,142.2%and 133.8%;Day 4,134.7%and 131.0%;Day 5,133.5%and 136.2%;all P<0.05),and VM formation assay suggested that hypoxia increased angiogenesis of MHCC97H and SMCC7721 cells. Whereas dexmedetomidine significantly inhibited the proliferation(Dex+CoCl2 group vs CoCl2 group,the proliferation rate of MHCC97H and SMCC7721:Day 3,55.7%vs 60.7%;Day 4,46.9%vs 58.1%;Day 5,46.4%vs 57.0%,all P<0.05)and angiogenesis of MHCC97H,SMCC7721 cells induced by hypoxia. Dexmedetomidine may exert these functions by activating α-2A adrenergic receptor,causing an decrease in HIF-1a and VEGF protein,while hypoxia activated HIF-1a and VEGF protein to promote the growth and angiogenesis of cells.[Conclusion]The findings provide evidence that hypoxia could promote the proliferation and angiogenesis of MHCC97H and SMCC7721 cells,while dexmedetomidine might inhibit these effects by down-regulating HIF-1a and VEGF protein expression through activatingα-2A adrenergic receptor.
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Objective To establish a rabbit model of acute lung injury induced by one-lung ventilation (OLV) .Methods Sixteen New Zealand white rabbits weighing 2.3-2.7 kg were randomly divided into 2 groups (n=8 each):conventional tidal volume(VT) group (group Ⅰ) and high VT group (group Ⅱ).All the rabbits were tracheostomized and a tracheal tube was inserted into the right bronchus for right lung ventilation in the two groups. VT was set at 6 ml/kg in group Ⅰ and at 12 ml/kg in group Ⅱ and the other ventilatory parameters were the same in the two groups (FiO2 50% , RR 40 bpm, I∶E=1∶2). Immediately before OLV(T0) and at 1, 2 and 3 h of OLV (T1-3), peak airway pressure was measured and arterial blood samples were taken for blood gas analysis and oxygenation index (OI) was calculated. The animals were sacrificed at 3 h of OLV and lung tissues obtained for microscopic examination.The lung injury was scored. W/D lung weight ratio was calculated. Bron-choalveolar lavage fluid (BALF) was collected for measurement of protein concentrations and neutrophil counts. Results The peak airway pressure was significantly higher at T1-3 in group Ⅱ and OI was significantly lower at T2,3 in the two groups than those at T0(P＜0.05) .W/D lung weight ratio and lung injury scores of the right lung were significantly lower than those of the left lung in the two groups(P＜0.05).The peak airway pressure was significantly higher at T1-3, OI was significantly lower at T3, and W/D lung weight ratio, protein concentrations and neutrophil counts in BALF and lung injury scores of the right lung were significantly higher in group Ⅱ than in group Ⅰ(P＜0.05). Conclusion OLV with VT of 12 ml/kg for 3 h can successfully establish a rabbit model of acute lung injury.
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Objective To investigate the influence of acute hypervolemic hemodilution (AHH) on pharmacodaynamics of cisatracurium in patients undergoing general anesthesia. Methods Sixty ASA Ⅰ or Ⅱ patients aged 18-60 yr scheduled for major abdominal surgery under general anesthesia were randomly allocated into 2 groups (n = 30 each): control group and AHH group. Each group was further divided into 3 subgroups according to the initial dose of cisatracurium (30, 40, 50 μg/kg) . The radial artery and right internal jugular vein were cannulated. BP, HR, CVP, SpO_2, P_(ET) CO_2 and body temperature were continuously monitored. The response of left adductor pollicis muscle to TOF stimulation of ulna nerve was monitored using TOF- Watch~R SX (Organon). Both groups received 10 ml/kg multiple electrolyte solution (plasma-Lyte A) during induction of anesthesia. In group AHH 15 ml/kg 6% hydroxyethyl starch (HES) 130/0.4 solution was infused via internal jugular vein over 30-40 min in addition to plasma-Lyte A. Five minutes after completion of plasma-Lyte A or HES, cisatracurium 30, 40 or SO fig/kg was injected iv in the respective subgroups. After the maximal T_1 block was achieved, the second dose was given to reach a total dose of 100 μg/kg. The onset time, duration of clinical action, total duration of action and recovery index were recorded. The doses for 50% , 90% and 95% T_1 depression (ED_(50), ED_(90), ED_(95)) were calculated by Probit method. Results The ED_(50), ED_(90), ED_(95) of cisatracurium were significantly higher in AHH group than in control group. The onset time of cisatracurium was significantly longer but clinical and total duration of action was significantly shorter in AHH group than in control group. There was no significant difference in recovery index between the two groups. Conclusion AHH can decrease the potency of cisatracurium.
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Objective To investigate the practical value of Shikani optical stylet used for orotracheal intubation in critically conscious patients and to evaluate the successful rate. Method A total of 48 conscious patients with severe respiratory failure were selected from January 2008 to June 2009. Of them, there were 31 males and 17 females,aging 21-86 years old with an average of 57 years old. All enrolled patients needed endotracheal intubation for mechanical ventilation support, and they were assigned to Shikani group (group S, n = 25) and Macintosh group (group M, n = 23) according to the odd and even number of date of admission to this study. The time consumed for intubation, the number of failure in intubation, the adverse effects or complications such as hemodynam-ic changes, injury to the pharyngo-oral cavity, choking and breath-hold were observed and recorded. The rank test and chi-square test were used for statistical analysis. Results The ratio of the successful intubation at first attempt was much higher in group S (96.0%) than that in group M (60.9%) (P <0.01). Compared with group M, the time consumed for intubation was significantly shortened, the cardiovascular reactions were much mild, and the incidence of injury to pharyngo-oral cavity, choking and breath-hold were less in the group S ( P < 0.01 all). Conclusions For the acute and critical patients, especially the conscious ones, orotracheal intubation with the Shikani optical stylet is rapid, successful, safe and less injurious, resulting in mild cardiovascular reactions.
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Objective To investigate the effect of propofol on the function of gap junction (GJ) in HeLa cells transfected with Cx32/Cx26 plasmid. Methods Cervical cancer HeLa cells transfected with Cx32/Cx26 was given as present by professor Andrew L. Harris from New Jersey Dental Medical School, department of pharmacology and physiology. The transfected cells were selected by G-418. The effective GJ channels were identified by "Parachute Assay". The cells were randomly divided into 6 groups: Ⅰ control group (group C); Ⅱ fat emulsion group was exposed to fat emulsion 10 μg/ml (group E); Ⅲ 18-α-GA group was exposed 18-α-GA (gap junction blocker) 1.0 μg/ml (18-α-GA); Ⅳ, Ⅴ, Ⅵ propofol groups were exposed to propofol 1.3, 2.2 and 3.2μg/ml respectively (group P1, P2, P3). The transfected HeLa cells were incubated at 37 ℃ for 4 h. Gap junction function was assessed using fluorescent indicators Calcine-AM which emits green fluorescence and CM-Dil which emits red fluorescence. The small molecular Calcine-AM can pass through gap junction and enters HeLa cells while the large molecular CM-Dil cannot pass through gap junction and stays in the loading cells. Fluorescent indicator transmissibility and inhibition rate were calculated. Results The fluorescent indicator transmissibility was significantly lower and inhibition rate higher in group 18-α-GA, P1, P2 and P3 than in control group. There was nosignificant difference in the fluorescent indicator transmissibility and inhibition rate between group C and E. The inhibition of GJ function by propofol was dose-dependent. Conclusion Propofol can inhibit the function of GJ in HeLa cells transfected by Cx32/Cx26 in a dose-dependent manner.