ABSTRACT
Objective To investigate the effects of curcumin (Cur) on activation of spinal Toll-like receptor 4 (TLR4) and on the chronic antinociceptive tolerance of morphine.Methods Sixty male Sprague-Dawley rats with successful intrathecal catheterization were randomly divided into four groups (n=15):saline (NS) group;morphine (MOR) group;curcumin (Cur) group and morphine plus curcumin (MOR+Cur) group.A morphine tolerance model of rats was induced by intrathecal ifjection of morphine 15μg,once a day for 7 consecutive days in MOR and MOR+Cur group;100μg curcumin was administered intrathecally once a day for 7 consecutive days in Cur and MOR+Cur group,10μl saline was administered intrathecally once a day for 7 consecutive days in NS group.The effect of curcumin intrathecal catheterization on morphine antinociceptive tolerance was explored by the tail flick latency (TFL) method and mechanical withdrawal threshold (MWT),and then the maximum possible potential effect (MPE) was calculated.The immunofluorescence staining method was applied to detect the effect of curcumin on the activation of lumbar spinal microglia.Real-time PCR and Western blotting were used to evaluate the effect of curcumin on the expression of mRNA and protein of spinal TLR4.Results The ％MPE TFL and ％MPE MWT increased significantly in MOR+Cur group than in MOR group (P＜0.05) after 7 days of intrathecal injection of morphine,intrathecal injection of curcumin and saline failed to induce analgesic effect.There was no significant difference in MPE between Cur group and NS group (P＞0.05).The lumbar spinal microglia increased markedly and the expressions of polyclonal antibody IBA-1 and TLR4 were significantly up-regulated in MOR group than in NS group (P＜0.05).The lumbar spinal microglia decreased obviously and the expressions of IBA-1 and TLR4 were significantly down-regulated in MOR+Cur group as compared with that in MOR group (P＜0.0S),but there was no significant difference in the expressions of IBA-1 and TLR4 between Cur group and NS group (P＞0.05).Conclusion Curcumin may attenuate chronic morphine antinociceptive tolerance through inhibiting spinal TLR4 up-regulation.
ABSTRACT
<p><b>BACKGROUND</b>Sevoflurane is currently used as a volatile inhalation anesthetic with many clinical advantages. A representative degradation product, compound A, was quantitatively measured to investigate whether there are different reactions between two kinds of water content sevoflurane formulations with different carbon dioxide (CO2) absorbents.</p><p><b>METHODS</b>A closed-circle breathe bag with the Dräger Fabius GS anesthesia apparatus was used as an artificial rubber lung. The experiments were grouped according to different sevoflurane formulations: group A: higher-water sevoflurane (Ultane); group B: lower-water sevoflurane (Sevoness). During the experiment, CO2 (200 ml/min) was continually perfused to keep the end-tidal pressure of CO2 (P(ET)CO2) at 35 - 45 mmHg. The artificial ventilation was set to 6 L/min, and the breathing rate at 12 breaths/min. The circuit was operated with constant fresh gas flow rate (1 L/min) and the sevoflurane concentration was kept at 1.0 minimum alveolar concentration (MAC) for 240 minutes. At 0, 10, 20, 30, 60, 90, 120, 180 and 240 minutes, gas was collected from the Y-piece. Gas chromatography/mass spectrometry (GC/MS) was used to quantify the major degradation product, compound A, with different water content sevoflurane. PETCO2 and sevoflurane concentration, and the temperature of the canister were continuously monitored during the experiment.</p><p><b>RESULTS</b>There were no significant differences in P(ET)CO2 and sevoflurane concentrations between the two groups. Drägersorb 800 plus produced the highest concentrations of compound A compared with other sodalimes, and Sevoness in Drägersorb 800 plus generated more compound A than Ultane (P < 0.05). There were significant differences in the peak and average compound A concentrations between Ultane and Sevoness with Drägersorb 800 plus (P < 0.05), while the compound A concentration produced by Sodasorb grase and sofonolime in the two groups showed no significant difference (P > 0.05). In the same group, the peak and average of compound A concentration produced by Sodasorb grase and sofonolime showed significant difference with Drägersorb 800 plus (P < 0.05).</p><p><b>CONCLUSION</b>The water content of sevoflurane and potassium hydroxide in CO2 absorbent can influence compound A production.</p>