ABSTRACT
Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in spinal dorsal horn in dexmedetomidine-induced reduction of neuropathic pain (NP) in rats.Methods:Forty clean-grade healthy male Sprague-Dawley rats, aged 7-9 weeks, weighing 190-240 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), sham operation group (group SH), group NP, dexmedetomidine group (group D), and specific HDAC6 inhibitor ACY-1215 plus dexmedetomidine group (group AD). The animals were commonly fed without any treatment in group C. The sciatic nerve was only isolated but not ligated in group SH.The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.NP was induced by chronic constrictive injury (CCI). The right sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1-mm intervals with 4-0 silk thread in NP and D groups.In group D, dexmedetomidine 40 μg/kg was intraperitoneally injected once a day starting from the end of operation until the animals were sacrificed.In group AD, ACY-1215 25 mg/kg was intraperitoneally injected every day immediately before CCI, and dexmedetomidine 40 μg/kg was intraperitoneally injected daily after CCI until 15 days after CCI.The equal volume of solvent was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (baseline, T 0) and 3, 6, 9, 12 and 15 days after CCI (T 1-5). The rats were then sacrificed, and the dorsal horn tissues of L 4-6 spinal cord were obtained for determination of the expression of myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB) p65 by Western blot. Results:Compared with group C and group SH, the MWT was significantly decreased, and the TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was up-regulated in NP, D and AD groups ( P<0.05). Compared with group NP, the MWT was significantly increased, and the TWL was prolonged at T 1-5, the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was down-regulated in group D ( P<0.05), and no significant change was found in the parameters mentioned above in group AD ( P>0.05). Compared with group D, MWT was significantly decreased, and TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 was up-regulated in the dorsal horn of the spinal cord in group AD ( P<0.05). Conclusion:HDAC6 in spinal dorsal horn is involved in dexmedetomidine-induced reduction of NP in rats, which is related to inhibiting MyD88/NF-κB signaling pathway.
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Objective:To evaluate the effect of ulinastatin on hyperoxia-induced acute lung injury (ALI) and its relationship with Wnt/β-catenin signaling pathway in infantile rats.Methods:A total of 36 clean-grade Sprague-Dawley rats, aged 14 days, weighing 40-50 g, were divided into 3 groups ( n=12 each): control group (C group), hyperoxia-induced ALI group (ALI group) and ulinastatin group (UTI group). Hyperoxia-induced ALI was induced by inhaling oxygen at concentration greater than 90% for 72 h. At 1 day after the model was established successfully, ulinastatin 50 000 U/kg was injected intraperitoneally daily at the same time for 3 consecutive days in group UTI, while the equal volume of normal saline was injected intraperitoneally at the same time point in C and ALI groups.The animals were sacrificed at 4 days after the model was established successfully, the lung tissues were taken for determination of the wet/dry weight ratio (W/D ratio), for microscopic examination of the pathological changes which were scored, for measurement of interleukin-6 (IL-6) IL-1β and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylated glycogen synthase kinase (p-GSK-3β), Wnt3a and β-catenin by Western blot, and ultrastructure was examined with with an electron microscope. Results:Compared with C group, W/D ratio and lung injury score were significantly increased, the contents of IL-6, IL-1β and TNF-α were increased, and the expression of p-GSK-3β, Wnt3a and β-catenin were up-regulated in lung tissues in group ALI ( P<0.05). Compared with group ALI, W/D ratio and lung injury score were significantly decreased, the contents of IL-6, IL-1β and TNF-α were decreased, and the expression of p-GSK-3β, Wnt3a and β-catenin were down-regulated in lung tissues in group UTI ( P<0.05). The ultrastructure injury in group UTI was reduced as compared with group ALI. Conclusion:The mechanism by which ulinastatin can alleviate hyperoxia-induced ALI is related to inhibiting the activation of Wnt/β-catenin signaling pathway and decreasing inflammatory response in infantile rats.
ABSTRACT
Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on Toll-like receptor 4 (TLR4) /nuclear factor kappa B (NF-κB) signaling pathway in non-ventilated lung injury in the patients undergoing radical operation for lung cancer.Methods A total of 100 patients,aged 40-64 yr,with body mass index 18-27 kg/m2,of American Society of Anesthesiology physical status Ⅱ or Ⅲ,undergoing radical operation for lung cancer,were divided into 2 groups (n=50 each) according to the random number table method:control group (group C) and PHC group.PHC 0.01 mg/kg was intravenously injected at 10 min before anesthesia induction in group PHC,while the equal volume of normal saline was given instead in group C.The peripheral tissues of the removed lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio).The pathological changes and ultrastructure of lung tissues were observed under light microscope,and lung injury was assessed and scored.The expression of TLR4 and NF-κB protein and mRNA was detected by Western blot and real-time polymerase chain reaction,respectively.Before administration (T0),at the onset of one-lung ventilation (T1),at 60 min of one-lung ventilation (T2),immediately after the end of one-lung ventilation (T3),at the end of operation (T4) and at 24 h after operation (T5),blood samples were collected from the internal jugular vein for determination of serum tumor necrosis factor-alpha,interleukin-6 (IL-6) and IL-8 concentrations by enzyme-linked immunosorbent assay.Results Compared with group C,the W/D ratio and lung injury scores were significantly decreased,the expression of TLR4 and NF-κB protein and mRNA was down-regulated,and the concentrations of tumor necrosis factor-alpha,IL-6 and IL-8 were decreased at T12-T5 in group PHC (P＜0.05).The pathological changes and damage to ultrastructure of lung tissues were significantly attenuated in group PHC as compared with group C.Conclusion The mechanism by which PHC attenuates non-ventilated lung injury is related to blocking TLR4/NF-κB signaling pathway and reducing inflammatory responses in the patients undergoing radical operation for lung cancer.
ABSTRACT
Objective@#To evaluate the effect of penehyclidine hydrochloride (PHC) on Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in non-ventilated lung injury in the patients undergoing radical operation for lung cancer.@*Methods@#A total of 100 patients, aged 40-64 yr, with body mass index 18-27 kg/m2, of American Society of Anesthesiology physical status Ⅱ or Ⅲ, undergoing radical operation for lung cancer, were divided into 2 groups (n=50 each) according to the random number table method: control group (group C) and PHC group.PHC 0.01 mg/kg was intravenously injected at 10 min before anesthesia induction in group PHC, while the equal volume of normal saline was given instead in group C. The peripheral tissues of the removed lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio). The pathological changes and ultrastructure of lung tissues were observed under light microscope, and lung injury was assessed and scored.The expression of TLR4 and NF-κB protein and mRNA was detected by Western blot and real-time polymerase chain reaction, respectively.Before administration (T0), at the onset of one-lung ventilation (T1), at 60 min of one-lung ventilation (T2), immediately after the end of one-lung ventilation (T3), at the end of operation (T4) and at 24 h after operation (T5), blood samples were collected from the internal jugular vein for determination of serum tumor necrosis factor-alpha, interleukin-6 (IL-6) and IL-8 concentrations by enzyme-linked immunosorbent assay.@*Results@#Compared with group C, the W/D ratio and lung injury scores were significantly decreased, the expression of TLR4 and NF-κВ protein and mRNA was down-regulated, and the concentrations of tumor necrosis factor-alpha, IL-6 and IL-8 were decreased at T2-T5 in group PHC (P<0.05). The pathological changes and damage to ultrastructure of lung tissues were significantly attenuated in group PHC as compared with group C.@*Conclusion@#The mechanism by which PHC attenuates non-ventilated lung injury is related to blocking TLR4/NF-κВ signaling pathway and reducing inflammatory responses in the patients undergoing radical operation for lung cancer.