Effect of remifentanil combined anesthesia on cytokines and oxidative stress in patients undergoing laparoscopic surgery for colon cancer

Objective: To investigate the effect of remifentanil combined anesthesia on serum cytokines and oxidative stress indices in patients undergoing laparoscopic surgery for colon cancer

Study design: Experimental study

Place and duration of study: Department of anesthesiology, Yuhuangding Hospital affiliated to Qingdao University, Yantai, China, from may 2016 to march 2018

Methodology: A total of 154 patients undergoing laparoscopic surgery for colon cancer were randomly divided into control group and observation group, with 77 cases in each group. Control group received fentanyl combined anesthesia, and observation group received remifentanil combined anesthesia. Levels of serum cytokines IL-8, IL-6, CRP, TNF- alpha; and the levels of oxidative stress indices SOD, MDA, CAT, and GSH on the first day after operation were compared. Occurrence of adverse reactions during anesthesia recovery was observed and recorded in both groups

Results: On the first day after surgery, levels of serum cytokines IL-8, IL-6, CRP, TNF- alpha; and MDA in the observation group were lower than those in the control group [all p<0.001]; levels of serum SOD, GSH, and cat in the observation group were higher than those in the control group [all p<0.001]. The frequency of adverse reactions such as nausea and vomiting, chills, restlessness, cough, and tachycardia in the observation group was lower than that in the control group [p=0.029, 0.016, 0.009, 0.025, and 0.003, respectively]

Conclusion: Compared with fentanyl combined anesthesia, the remifentanil combined anesthesia can significantly reduce serum levels of cytokines IL-8, IL-6, CRP, TNF- alpha; and oxidative stress level, and is, therefore, more secure for patients undergoing laparoscopic surgery for colon cancer

miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/β-Catenin Pathway by Targeting Wnt1

PURPOSE: Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain. miR-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment. However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear. MATERIALS AND METHODS: C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days. miR-34a expression was reduced through intracerebroventricular injection with miR-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure. Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis. Spatial memory ability was evaluated by the Morris water maze test. The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining. The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/β-catenin pathway-related proteins were evaluated using Western blot analysis. RESULTS: Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment. miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons. Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons. Increased expression of miR-34a inhibited the Wnt/β-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects. CONCLUSION: miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/β-catenin pathway by targeting Wnt1.

Effect of isoflurane on expression of p-GSK-3β and β-catenin in neural stem cells in hippocampus of developing rats / 中华麻醉学杂志

Objective To evaluate the effect of isoflurane on the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and β-catenin in neural stem cells (NSCs) in the hippocampus of developing rats.Methods Twenty-four 7-day-old Sprague-Dawley rats,weighing 15-20 g,were divided into 2 groups (n =12 each) using a random number table:control group (group C) and 2％ isoflurane group (group Ⅰ).Group C inhaled 30％ oxygen for 4 h.Group Ⅰ inhaled 2％ isoflurane in 30％ oxygen for 4 h.Six rats were randomly selected from each group,and 5-bromodeoxyuridine (BrdU) 200 mg/kg was intraperitoneally injected immediately before anesthesia to assess the proliferation of NSCs in the hippocampal dentate gyrus.The rats were sacrificed at 6 h after the end of anesthesia,and hippocampi were isolated for determination of the number of BrdU positive cells in the dentate gyrus (by immunohistochemistry) and expression of p-GSK-3β and β-catenin in hippocampal tissues (by Western blot analysis).Results Compared with group C,the number of BrdU positive cells was significantly decreased,and the expression of p-GSK-3β and β-catenin was down-regulated in group Ⅰ (P＜0.05).Conclusion Isoflurane can inhibit the proliferation of NSCs in the hippocampal dentate gyrus of developing rats,and the mechanism may be related to down-regulation of the expression of p-GSK-3β and β-catenin.

Effect of isoflurane anesthesia on Wnt3a expression in hippocampus of developing rats / 中华麻醉学杂志

Objective To evaluate the effect of isoflurane anesthesia on Wnt3a expression in the hippocampus of developing rats.Methods Twenty-four 7-day-old male Sprague-Dawley rats,weighing 125-155 g,were randomly divided into 3 groups (n=8 each) using a random number table:control group (group C),4 h inhalation of 2％ isoflurane group (group I4),and 6 h inhalation of 2％ isoflurane group (group I6).The rats were sacrificed at 6 h after the end of treatment in each group,and the hippocampi were removed for determination of Wnt3a mRNA expression (by real-time reverse transcriptase polymerase chain reaction) and Wnt3a expression (by Western blot).Results Compared with group C,the expression of Wnt3a and Wnt3a mRNA in hippocampi was significantly up-regulated in I4 and I6 groups (P＜0.05).Compared with group I4,the expression of Wnt3a in hippocampi was significantly up-regulated (P＜0.05),and no significant change was found in the expression of Wnt3a mRNA in hippocampi in group I6 (P＞0.05).Conclusion The mechanism of isoflurane-induced neurotoxicity is probably related to upregulation of Wnt3a expression in the hippocampal tissues of developing rats.

Effects of minute quantity of endogenous endotoxin from the lung on ventilator-induced lung injury in rats / 中华麻醉学杂志

Objective To investigate the effects of minute quantity of endogenous endotoxin originating from the lung on ventilator-induced lung injury in rats. Methods Thirty-two pathogen-free male adult SD rats weighing 370-390 g were randomly divided into 4 groups ( n = 8 each): group I spontaneous breathing (group C) ; group Ⅱ spontaneous breathing + IPS (group CL) ; group IE mechanical ventilation (group M) and group IV mechanical ventilation + LPS (group ML). The animals were anesthetized with intraperitoneal 20% urethane 0.8 ml/100 g. Right common carotid artery and left femoral vein were cannulated for BP monitoring and fluid and drug administration. The animals were tracheostomized. In group CL and ML LPS 100μg /kg was instilled into trachea. In group M and ML the animals were mechanically ventilated (V_T 20 ml/kg, PEEP=0, I = E = 1:1). P_(ET) CO_2 was maintained at 35-45 nun Hg by adjusting respiratory rate. The animals were breathing or ventilated with room air,and ECG, BP, HR and P_(ET)CO_2 were continuously monitored. Blood gases were analyzed at the beginning and 1, 2 and 3 h of experiment. The animals were sacrificed at 3 h of experiment. The lungs were removed for microscopic examination. The pathological changes of the lung were scored (0 = normal,3 = severe change) . Wet/dry lung weight ratio was determined. The left lung was lavaged. The broncho-alveolar lavage fluid (BALF) was collected. WBCs in BALF were counted. Pulmonary albumin permeability (PAP) (BALF protein concentration/plasma protein concentration) was determined. Plasma TNF-a and macrophage inflammatory protein 2 (MIP-2) concentrations were detected with ELISA. The endotoxin receptor CD14 mRNA expression in lung tissue was determined by RT-PCR and the macrophage CD14 expression in BALF was determined by immuno histochemistry in group C and M. Results Wet/dry lung weight ratio and PAP were significantly higher in group ML than in group M and C. WBC count in BALF, the pathological score and plasma MIP-2 concentration were significantly higher in group M and ML than in group C and were significantly higher in group ML than in group M. TNF-a concentration was significantly higher in group CL and ML and was not detected in group C and M. CD14mRNA expression in the lung tissue and CD14 expression in BALF macrophage were significantly higher in group M than in group C. Conclusion Minute amount of endogenous endotoxin from the lung can aggravate ventilator-induced lung injury in rats. Mechanical ventilation with large tidal volume sensitizes the lung to LPS stimulation through up-regulation of CD14 exexpression.