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Objective:To investigate the effects of subanesthetic concentration of sevoflurane on the plasticity of dendritic spines in the prefrontal cortex neurons of juvenile rats.Methods:Thirty-six clean-grade male Sprague-Dawley rats, aged 24 days, weighing 50-60 g, were divided into control group (group C) and sevoflurane anesthesia group (group S) using a random number table method, with 18 rats in each group.Group S inhaled 1.2% sevoflurane and 50% oxygen (flow rate 1 L/min) for 3 h, while group C inhaled 50% oxygen (flow rate 1 L/min) for 3 h. Open-field test and Morris water maze test were performed at 3 days after anesthesia.Animals were sacrificed, and brain samples were then taken for determination of the number of apoptotic neurons in layer Ⅱ-Ⅲ of the prefrontal cortex, density of dendritic spines, and expression of postsynaptic density protein 95 and gephyrin by TUNEL staining, Golgi staining or Western blot.Results:Compared with group C, no significant change was found in total distance or time of staying at the central region in the open-field test or the average swimming velocity, escape latency or the number of apoptotic neurons in the Morris water maze test ( P>0.05), and the density of dendritic spines was significantly increased, and the expression of postsynaptic density protein 95 and gephyrin was up-regulated in group S ( P<0.05). Conclusion:Subanesthetic concentration of sevoflurane can enhance the plasticity of dendritic spines in the prefrontal cortex neurons of juvenile rats.
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<p><b>OBJECTIVE</b>To determine whether quercetin inhibits oxidized low-density lipoprotein (Ox-LDL)-induced osteogenic differentiation and calcification of vascular smooth muscle cells (VSMCs) and understand the underlying mechanism.</p><p><b>METHODS</b>The calcification of human VSMCs following Ox-LDL treatment was assessed using alizarin red staining and by detecting ALP activity. The mRNA expressions of the bone-related genes including Msx2, BMP2 and Osterix, and the contractile proteins including SMA and SM22a were analyzed using qPCR. The effects of quercetin were investigated on OxLDL-induced VSMC calcification and changes in ALP activity, expressions of Msx2, BMP2, Osterix, SMA and SM22a, ROS levels and SOD activity. The effect of Toll like receptor 4 (TLR4) silencing mediated by siRNA transfection on cell calcification, ALP activity, gene expressions and ROS levels were investigated.</p><p><b>RESULTS</b>Ox-LDL treatment promoted VSMC calcification and up-regulated TLR4 expression. Quercetin treatment significantly attenuated Ox-LDL-induced VSMC calcification, reduced ALP activity, down-regulated the expression levels of Msx2, BMP2 and Osterix, and up-regulated the expressions of vascular smooth muscle contractile proteins SMA and SM22a. In addition, Quercetin treatment markedly increased SOD activity, reduced ROS levels and TLR4 expression in VSMCs. Silencing TLR4 expression using TLR4 siRNA also significantly decreased calcification of the VSMCs.</p><p><b>CONCLUSIONS</b>Quercetin inhibits Ox-LDL-induced VSMC calcification in VSMCs possibly by targeting the ROS/TLR4 signaling pathway.</p>
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<p><b>OBJECTIVE</b>To study protective effect of ulinastatin on perioperative cardiac function in elderly patients undergoing major gastrointestinal surgery.</p><p><b>METHODS</b>Sixty elderly patients (32 male and 28 female patients) aged 60-82 years scheduled for major gastrointestinal surgery were randomized into ulinastatin group and control group. The patients in ulinastatin group received 2×10(5) U ulinastatin rapidly administered via a intravenous pump immediately before operation with subsequent continuous infusion at the rate of 1×10(5) U until the completion of surgery, and those in the control group received the same amount of saline instead. In both groups, the mean arterial pressure (MAP), heart rate (HR), left ventricular ejection fraction (LVEF), and cardiac output (CO) were monitored immediately before surgery (T0) and at 1 h (T1), 2 h (T2) and 3 h (T3) after the start of surgery. The total dopamine dose used was recorded at the end of surgery, and blood samples were collected at T0 and at 6 h (T4) and 12 h (T5) after the operation for determination of serum levels of cTn, CK-MB and BNP.</p><p><b>RESULTS</b>In both groups, MAP, LVEF and CO were significantly decreased at T2 and T3 (P<0.05) and serum levels of cTn, CK-MB and BNP significantly increased at T4 and T5 compared to those at T0 (P<0.05). Compared with the control group, the patients in ulinastatin group showed significantly higher MAP, LVEF and CO at T2 and T3 and lower serum levels of cTn, CK-MB and BNP at T4 and T5.</p><p><b>CONCLUSION</b>Ulinastatin offers effective perioerative cardiac protection in elderly patients undergoing major gastrointestinal surgery.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Cardiotonic Agents , Pharmacology , Creatine Kinase, MB Form , Metabolism , Digestive System Surgical Procedures , Glycoproteins , Pharmacology , Intraoperative Period , Natriuretic Peptide, Brain , Metabolism , Stroke VolumeABSTRACT
Objective To investigate the relationship between autophagy in spinal dorsal horn and development of morphine tolerance in rats.Methods Twenty-four healthy male Sprague-Dawley rats,in which intrathecal (IT) catheters were successfully placed,were randomly divided into 3 groups (n =8 each):control group (group C),morphine tolerance group (group M) and morphine + rapamycin as a reinforcing agent for autophagy group (group MR).Morphine tolerance was induced with IT morphine 20 μg twice a day for 7 consecutive days.While the equal volume of normal saline was given in group C.In addition,rapamycin 2.3μg was injected intrathecally at the second injection of morphine on 3rd day lasting for 3 consecutive days in group MR.Mechanical withdrawal threshold (MWT) to yon Frey filament stimulation was measured before IT injection and 30 min after the second IT injection on 1st,3rd,5th and 7th days.The rats were sacrificed 1 h after the last MWT measurement and the L4-6 segment of the spinal cord was removed for determination of the total mammalian target of rapamycin (mTOR) and phosphorylated mTOR(p-mTOR) and autophagy marker protein LC3 Ⅱ expression in spinal dorsal horn by Western blot.The percentage of p-mTOR expression in total mTOR expression was considered as reflection of the activity.Results MWT was gradually decreased with the prolongation of time of IT injection (P ＜ 0.05).Compared with group C,MWT was significantly increased during IT injection,mTOR activity was decreased and LC3 Ⅱ expression was up-regulated in groups M and MR (P ＜ 0.05).Compared with group M,MWT was significandy increased on 3rd,5th and 7th days after IT injection,mTOR activity was decreased and LC3 Ⅱ expression was up-regulated in group MR (P ＜ 0.05).Conclusion Increased autophagy in spinal dorsal horn is the regulatory mechanism of the body during the development of morphine tolerance in rats and can delay the development of morphine tolerance.
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In this study, we tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptors. The poly A m RNA from muscle by isolation were microinjected into Xenopus oocytes for receptor expression. Concentration-effect curves for the inhibition of Ach-induced currents were established for vecuronium, rocuranium, and isoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the isoflurane at a concentration equivalent to half the concentration producing a 50% inhibition alone. All tested drugs produced rapid and readily reversible concentration-dependent inhibition. The 50% inhibitory concentration values were 889 micromol/L (95% CI: 711-1214 micromol). 33.4 micromol (95% CI: 27.1-41.7 nmol) and 9.2 nmol (95% CI: 7.9-12.3 nmol) for isoflurane. rocuranium and vecuronium, respectively. Coapplication of isoflurane significantly enhanced the inhibitory effects of rocuranium and vecuronium, and it was especially so at low concentration of NMDRs. Isoflurane increases the potency of NDMRs, possibly by enhancing antagonist affinity at the receptor site.
Subject(s)
Androstanols/pharmacology , Anesthetics, Inhalation/pharmacology , Drug Synergism , Isoflurane/pharmacology , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Oocytes , Receptors, Nicotinic/drug effects , Vecuronium Bromide/pharmacology , Xenopus laevisABSTRACT
In this study, we tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptors. The poly A m RNA from muscle by isolation were microinjected into Xenopus oocytes for receptor expression. Concentration-effect curves for the inhibition of Ach-induced currents were established for vecuronium, rocuranium, and isoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the isoflurane at a concentration equivalent to half the concentration producing a 50% inhibition alone. All tested drugs produced rapid and readily reversible concentration-dependent inhibition. The 50% inhibitory concentration values were 889 micromol/L (95% CI: 711-1214 micromol). 33.4 micromol (95% CI: 27.1-41.7 nmol) and 9.2 nmol (95% CI: 7.9-12.3 nmol) for isoflurane. rocuranium and vecuronium, respectively. Coapplication of isoflurane significantly enhanced the inhibitory effects of rocuranium and vecuronium, and it was especially so at low concentration of NMDRs. Isoflurane increases the potency of NDMRs, possibly by enhancing antagonist affinity at the receptor site.