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Objective:To evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.
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Objective:To evaluate the role of acetaldehyde dehydrogenase 2 (ALDH2) in hippocampus in memory decline after myocardial ischemia-reperfusion (I/R) in rats.Methods:Twenty-four healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group S), myocardial I/R group (group I/R) and ALDH2 agonist ALDA-1 group (group ALDA-1). Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion in anesthetized animals.ALDA-1 10 mg/kg was intraperitoneally injected at 5 min before ischemia in group ALDA-1.The positioning navigation training in Morris water maze test was started from 6 days before developing the model.The spatial exploration in Morris water maze test was performed at 24 h after developing the model.The rats were sacrificed after the end of behavioral experiment, and the hippocampus was extracted for microscopic examination of the pathological changes (by hematoxylin and eosin staining) and for determination of the apoptosis index (AI) (by TUNEL staining), activity of ALDH2 (by colorimetry), contents of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) (by enzyme-linked immunosorbent assay), and expression of ALDH2 and 4-HNE (by Western blot). Results:Compared with group S, the number of crossing the original platform was significantly decreased, the time spent in the target quadrant was shortened, the activity of ALDH2 in the hippocampus was decreased, the expression of 4-HNE was up-regulated, and the contents of 4-HNE and MDA and AI were increased in group I/R ( P<0.05). Compared with group I/R, the number of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the ALDH2 activity was increased, the expression of 4-HNE was down-regulated, and the contents of 4-HNE and MDA and AI were decreased in group ALDA-1 ( P<0.05). There was no significant difference in ALDH2 expression in hippocampus among the three groups ( P>0.05). Conclusions:The mechanism of memory decline developed after myocardial I/R may be related to the decrease in ALDH2 activity and promotion of accumulation of aldehydes in the hippocampus of rats.
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Objective:To identify the potential pathogenic genes for perioperative neurocognitive disorder (PND) in the patients with digestive system tumors.Methods:The gene expression data of esophageal cancer, gastric cancer, colon cancer, rectal cancer and liver cancer in The Cancer Genome Atlas database were analyzed by bioinformatics analysis method, and the differentially expressed genes in tumor tissues in above-mentioned disease samples were identified compared with para-carcinoma tissues.Secretory proteome differential genes with the same expression trend in digestive system tumors were obtained by comparing with human secretory proteome genes.The correlation between secretomics and PND was determined by comparing with the GeneCards database.Hub genes were identified through PPI network construction and calculation, and the functions and signaling pathways of the above-mentioned differential genes were identified through GO and KEGG enrichment analysis.Results:Compared with para-carcinoma tissues, the expression of 2 640 genes was significantly up-regulated and the expression of 1 423 genes was down-regulated in esophageal cancer tissues; the expression of 3 748 genes was up-regulated and the expression of 908 genes was down-regulated in gastric cancer samples; the expression of 2 684 genes was up-regulated and the expression of 2 678 genes was down-regulated in colon cancer samples; the expression of 2 876 genes was up-regulated and the expression of 2 945 genes was down-regulated in rectal cancer samples; the expression of 1 484 genes was up-regulated and the expression of 723 genes was down-regulated in hepatocellular carcinoma samples.Among them, the expression of the encoding genes of 53 secreted proteins was uniformly up-regulated and the expression of the encoding genes of 20 secreted proteins was uniformly down-regulated in the above tumors.Twenty up-regulated genes and 3 down-regulated genes were associated with PND.PPI network analysis showed that MMP9 was the hub gene.The results of GO and KEGG analysis suggested that differentially expressed genes were mainly related to receptor-ligand activity, cytokine activity and chemokine activity, and were mainly enriched in signaling pathways related to cell cycle and cellular senescence.Conclusions:About 23 differentially expressed genes in digestive system tumors are potentially related to PND, of which MMP9 and other genes may be the hub genes, mainly acting on receptor-ligand binding, regulation of cytokine and chemokine activity, cell cycle, cellular senescence and other related signaling pathways.
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Objective To study the effect of dexmetomidine on tracheal intubation under abdominal anesthesia.Methods From January 2015 to January 2018,100 patients were selected to perform tracheal intubation under abdominal anesthesia in Shanxi Provincial Hospital of Taiyuan.A total of 100 patients under abdominal surgery were randomly divided into two groups,with 50 patients in each group.The observation group was given dexmetomidine intravenous injection during the operation,while the control group was not given dexmetomidine during the operation.The blood pressure and heart rate of the two groups were compared before and after anesthesia.The recovery time of spontaneous respiration,eye opening time,extubation time,incidence of adverse events,cough score and restlessness score were compared between the two groups,and the cognitive function of the two groups was compared.Results After anesthesia,the systolic blood pressure [(103.75 ± 2.26) mmHg],diastolic blood pressure [(71.92 ± 1.95) mmHg],heart rate[(70.91 ± 1.89) rpm] in the observation group were significantly higher than those in the control group [(100.37 ±2.91)mmHg,(70.27 ± 1.84)mmHg,(69.08 ±1.63)] (t =6.487,4.532,5.185,all P ＜0.05).The recovery time of spontaneous respiration [(7.14 ± 1.37) min],eye opening time [(9.85 ± 2.31) min] and extubation time[(20.57 ±2.94)min]in the observation group were significantly shorter than those in the control group[(8.75 ± 1.89)min,(12.41 ±2.97)min,(24.06 ±3.42)min] (t =4.877,4.811,5.472,all P ＜0.05).The incidence rate of adverse events in the observation group (8％) was lower than 24％ in the control group (x2 =4.762,P ＜ 0.05).The score of cough and the score of restlessness in the observation group were (4.09 ± 1.63) and (4.27 ± 1.96),respectively,which were significantly lower than those in the control group [(6.24 ± 2.18) and (6.51 ± 2.32)] (t =5.186,5.215,all P ＜ 0.05).At 6 h after operation,the scores of MMSE,vocabulary memory,simple calculation and picture memory in the observation group were (23.95 ±2.13),(7.35 ± 1.08),(7.14 ± 1.12) and (7.26 ± 1.17),respectively,which were higher than those in the control group[(20.47 ± 1.91),(6.17 ± 0.94),(5.89 ± 1.04),(6.02 ± 0.89)] (t =8.601,5.828,5.783,5.965,all P ＜ 0.05).Conclusion The application of dexmetomidine in patients under general anesthesia under tracheal intubation can effectively reduce the fluctuation of hemodynamic indicators after anesthesia,help to maintain the hemodynamic stability of patients,and promote the recovery of consciousness after operation.It can prevent adverse events during recovery of anesthesia and reduce the effect of anesthesia on cognitive function of patients.
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Objective To investigate the relationship between glycoprotein synthase kinase-3 (GSK-3β) and mitochondrial cleavage protein (Drp-1) during diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.Methods Clean-grade healthy male Sprague-Dawley rats,weighing 250-300 g,were used in this study.Diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 30 g/kg.Forty rats with diabetes mellitus were divided into 5 groups (n =8 each) using a random number table method:ischemia-reperfusion (I/R) group,sevoflurane postconditioning group (SP group),sevoflurane postconditioning plus Drp1 inhibitor Mivi-1 group (SM group),sevoflurane postconditioning plus GSK-3β inhibitor SB216763 group (SB group) and sevoflurane postconditioning plus Mivi-1 plus SB216763 group (SMB group).Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.The rats inhaled 2.5％ sevoflurane for 10 min starting from 5 min before reperfusion in SP,SM,SB and SBM groups.Mivi-1 1.2 mg/kg was injected via the caudal vein at 15 min before reperfusion in group SM.SB216763 0.2 mg/kg was injected via the caudal vein at 5 min before reperfusion in group SB.Mivi-1 1.2 mg/kg and SB216763 0.2 mg/kg were injected via the caudal vein at 15 and 5 min before reperfusion,respectively,in group SMB.Blood samples were collected from the abdominal aorta at 120 min of reperfusion for determination of serum cardiac troponin Ⅰ (cTnⅠ) concentrations.The rats were sacrificed and myocardial specimens were obtained from the apex for determination of the cell apoptosis (by TUNEL) and expression of caspase-3 (by Western blot),and apoptotic index (AI) was calculated.Results Compared with group I/R,no significant change was found in caspase-3 expression,AI or serum cTnⅠ concentrations (P＞0.05),and the pathological changes of myocardium were comparable in group SP,and the expression of caspase-3 was significantly down-regulated,and AI and serum cTnⅠ concentration were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SP,the expression of caspase-3 was significantly down-regulated,AI and serum cTnⅠ concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SMB or group SB,the expression of caspase-3 was significantly down-regulated,AI and serum cTnI concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in group SMB.Conclusion It is not a single regulatory relationship between GSK-3β and Drp-1 in the pathophysiological process of diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.
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Objective To evaluate the effect of ulinastatin on postoperative cognitive dysfunction in preoperative sleep deprived aged rats.Methods Sixty clean healthy male Sprague-Dawley rats,aged 18 months,weighing 350-500 g,were divided into 3 groups (n=20 each) using a random number table:control group (group C),sleep deprivation group (group D) and ulinastatin group (group U).Sleep deprivation was induced by using modified multiple platform method in D and U groups,and then splenectomy was performed in three groups.Ulinastatin 100 U/g was intraperitoneally injected before sleep deprivation and immediately after operation in group U.Ten rats were randomly selected at 3 days after operation and sacrificed,and hippocampi were removed for determination of the contents of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay.Morris water maze test was performed at 3-7 days after operation in the rest ten rats in each group,and the escape latency and time of staying at the original platform were recorded.Results Compared with group C,the escape latency was significantly prolonged at 4-6 days after operation,the time of staying at the original platform was shortened,and the contents of IL-1β,IL-6 and TNF-α were increased at 3 days after operation in D and U groups (P＜0.05).Compared with group D,the escape latency was significantly shortened at 4-6 days after operation,the time spent in the original platform was prolonged,and the contents of IL-1β,IL-6 and TNF-α were decreased at 3 days after operation in group U (P＜0.05).Conclusion Ulinastatin can mitigate postoperative cognitive dysfunction in preoperative sleep deprived aged rats,which is related to inhibiting inflammatory responses.
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Objective To evaluate the relationship between the failed mechanism of sevoflurane postconditioning-induced myocardial protection and the activity of dynamin-related protein 1(Drp1)in dia-betic rats. Methods Pathogen-free healthy adult male Sprague-Dawley rats, weighing 220-280 g, in which diabetes mellitus was induced by combination of high-fat and high-sucrose diet and intraperitoneal injection of streptozotoein 30 mg∕kg, were studied.Sixty rats with diabetes mellitus were divided into 5 groups(n=12 each)using a random number table: sham operation group(group Sham), myocardial ischemia∕reperfusion (I∕R)group(group I∕R), sevoflurane postconditioning group(group SP), Drp1 inhibitor mitochondrial division inhibitor-1(Mdivi-1)group(group M)and Mdivi-1 plus sevoflurane postconditioning group(group M-SP). Myocardial I∕R was induced by occluding the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion except for group Sham. Mdivi-1 1.2 mg∕kg was intraperito-neally injected at 15 min before ischemia in M and M-SP groups, and 2.5% sevoflurane was inhaled starting from 5 min of reperfusion in SP and M-SP groups. Blood samples were collected from the right internal jugular vein at 120 min of reperfusion for measurement of serum cardiac troponin I(cTnI)concentrations(by en-zyme-linked immunosorbent assay). Rats were then sacrificed and myocardial specimens were obtained for de-termination of the myocardial infarct size(by TTC), cell apoptosis(by TUNEL), expression of Bax, Bcl-2 and activated caspase-3(by Western blot)and nicotinamide adenine dinucleotide(NAD+)content(by spectrophotometry). Apoptosis index(AI)and Bax∕Bcl-2 ratio were calculated. Results Compared with group Sham, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax∕Bcl-2 ratio were significantly increased, the expression of activated caspase-3 was up-regulated, and the NAD+content was decreased in the other four groups(P<0.05). Compared with group I∕R, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax∕Bcl-2 ratio were significantly decreased, the expres-sion of activated caspase-3 was down-regulated, and the NAD+content was increased in group M-SP(P<0.05), and no significant change was found in the parameters mentioned above in SP and M groups(P>0.05). Compared with group SP, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax∕Bcl-2 ratio were significantly decreased, the expression of activated caspase-3 was down-regulated, and the NAD+content was decreased in group M-SP(P<0.05), and no significant change was found in the parameters mentioned above in group M(P>0.05). ConclusionThe failed mechanism of sevoflurane postconditioning-induced myocardial protection may be related to the activity of Drp1 in diabetic rats.
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Objective To investigate the effect of inhibition of glycogen synthase kinase?3 beta ( GSK?3β) activity on sevoflurane postconditioning?induced cardioprotection in diabetic rats. Methods Healthy adult male Sprague?Dawley rats, weighing 250-300 g, in which diabetes mellitus was induced by intraperitoneal 1% streptozotocin 60 mg∕kg combined with high?fat and high?sucrose diet and confirmed by blood glucose level >16. 7 mmol∕L. Forty rats with diabetes mellitus were divided into 5 groups ( n=8 each) using a random number table: sham operation group ( S group ) , ischemia?reperfusion ( I∕R ) group, sevoflurane postconditioning group ( SP group) , GSK?3β inhibitor SB216763 group ( SB group) , and sevoflurane postconditioning plus SB216763 group ( SS group ) . Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfu? sion. The rats inhaled sevoflurane with the end?tidal concentration of 2.5% for 5 min starting from 1 min be?fore reperfusion in group SP. SB216763 0.2 mg∕kg was injected via the caudal vein at 1 min before reperfu?sion in group SB. In group SS, the rats inhaled sevoflurane with the end?tidal concentration of 2.5% for 5 min starting from 1 min before reperfusion, and SB216763 0.2 mg∕kg was injected via the caudal vein at 1 min before reperfusion. At 120 min of reperfusion, blood samples were collected from the carotid artery for determination of serum creatine kinase?MB (CK?MB) activity and cardiac troponin I (cTnI) concentra?tions. Myocardial specimens were collected at 120 min of reperfusion for microscopic examination of the pathological changes and for determination of myocardial infarct size ( by 2,3,5?triphenyltetrazolium chlo?ride staining) and phosphorylated GSK?3β (p?GSK?3β) expression (by Western blot). Results Com?pared with group S, the myocardial infarct size and serum CK?MB activity and cTnI concentration were sig?nificantly increased, and the expression of p?GSK?3βwas significantly down?regulated in I∕R, SP, SB and SS groups (P0.05) . Compared with group SB, the myocardial infarct size and serum CK?MB activity and cTnI concentration were significantly decreased, and the expression of p?GSK?3β was sig?nificantly up?regulated in group SS (P<0.05). The pathological changes of myocardium were significantly attenuated in SB and SS groups as compared with group I∕R and group SP . Conclusion Inhibition of GSK?3β activity can improve sevoflurane postconditioning?induced cardioprotection in diabetic rats.