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Effects of curcumin on expression of receptor for advanced glycation end-products in spinal dorsal horn and dorsal root ganglion of rats with type 2 diabetic neuropathic pain

Xiaoting SHI ; Xia XU ; Hong CAO ; Jiajia LI ; Shaosheng WU ; Jun LI

Chinese Journal of Anesthesiology.2014;34(10):1207-1210. doi:10.3760/cma.j.issn.0254-1416.2014.10.014

Objective To evaluate the effects of curcumin on the expression of receptor for advanced glycation end-products (RAGE) in the spinal dorsal horn and dorsal root ganglion (DRG) of the rats with type 2 diabetic neuropathic pain (DNP).Methods Male Sprague-Dawley rats,weighing 160-180 g,were used in this study.Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet for 8 weeks and intraperitoneal streptozotocin (STZ) 35 mg/kg and confirmed by fasting blood glucose level ≥ 16.7 mmol/L 3 days later.Type 2 DNPwas confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) measured on day 14 after STZ administration less than 80％ of the baseline value.Eighty-one rats with type 2 DNP were randomly divided into 3 groups (n =27 each) using a random number table:DNP group,DNP + curcumin group (DCur group),and DNP+ solvent group (group DSC).In DCur and DSC groups,curcumin 100 mg· kg-1 · d-1 and corn oil 4 ml · kg-1 · d-1 were injected intraperitonally,respectively,for 14 consecutive days starting from the day 14 after STZ administration.Another 27 normal male Sprague-Dawley rats served as control group (group C) and were fed with normal forage.MWT and TWL were measured before STZ injection,at day 14 after STZ injection,and on 3,7 and 14 days after curcumin injection.RAGE positive cells were determined by immuno-histochemistry and the expression of RAGE by Western blot in the spinal dorsal horn and DRG after MWT and TWL were measured on 3,7 and 14 days after curcumin injection.Results Compared with group C,MWT was significantly decreased and TWL was shortened at 14 days after STZ injection and each time point after curcumin injection,the rate of RAGE positive cells in the spinal dorsal horn and DRG was increased at each time point after curcumin injection,and the expression of RAGE was up-regulated in the spinal dorsal horn at each time point after curcumin injection and in the DRG at 7 and 14 days after curcumin injection in group DNP.Compared with group DNP,MWT was significantly increased and TWL was prolonged at each time point after curcumin injection,the rate of RAGE positive cells in the spinal dorsal horn and DRG was significantly decreased at 7 and 14 days after curcumin injection,and the expression of RAGE was down-regulated in the spinal dorsal horn at each time point after curcumin injection and in the DRG at 7 and 14 days after curcumin injection in group DCur,and no significant change was found in the parameters mentioned above in group DSC.Conclusion The mechanism by which curcumin attenuates DNP may be related to inhibition of up-regulated expression of RAGE in the spinal dorsal horn and DRG of rats with type 2 diabetes mellitus.

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Effect of electro-acupunctare at Zusanli on liver injury in a rat model of sepsis after scald

Xuemin SONG ; Linli YUE ; Yi HAN ; Jianguo LI ; Zongze ZHANG ; Yanlin WANG

Chinese Journal of Anesthesiology.2014;34(10):1248-1251. doi:10.3760/cma.j.issn.0254-1416.2014.10.025

Objective To evaluate the effect of electro-acupunctare at Zusanli on liver injury in a rat model of sepsis after scald.Methods Fifty SPF male Sprague-Dawley rats,weighing 200-250 g,aged 2-3 months,were randomly divided into 5 groups (n =10 each) using a random number table:control group (group C); sepsis after scald group (group SS); electro-acupuncture at Zusanli group (group E); electric stimulation of non-acupoint group (group NE); electro-acupuncture at Zusanli + α-bungarotoxin (α-BGT) group (group α-BGT).The rats were subjected to a third degree scald covering 20％ of the total body surface area (TBSA) and sepsis was induced with muramyl dipeptide (MDP) 5 mg/kg injected into the femoral vein immediately after scald.Electro-stimulation (3 V,2 ms,3 Hz) of bilateral Zusanli acupoints or non-acupoints was performed for 12 min every 8 h for 2 consecutive days starting from the time point immediately after MDP was injected in group E.In group NE,electro-stimulation was performed at the points 5 mm lateral to the acupoints of bilateral Zusanli and the method was similar to those previously described in group E.In group α-BGT,α-BGT 1.0 μg/kg (in normal saline 1 ml) was injected into the femoral vein before electric stimulation,then electro-stimulation was performed and the method was similar to those previously described in group E.After 48 h of continuous stimulation,liver specimens were obtained for microscopic examination of the pathological changes.The blood samples were obtained from the abdominal aorta for determination of the levels of serum ALT and AST,tumor necrosis factor-alpha (TNF-α),and high mobility group box-1 (HMGB1) (by ELISA),and expression of Nod-like receptor 2 (NLR2) mRNA (by RTPCR) and receptor-interacting protein 2 (RIP2) in the liver tissues (by Western blot).Results The serum ALT and AST,TNF-α and HMGB-1 levels and NLR2 mRNA and RIP2 expression in liver tissues were significantly higher in SS group than in C group.Compared with SS group,the serum ALT,AST,TNF-α and HMGB1 levels were significantly decreased and NLR2 mRNA and RIP2 expression was down-regulated in E group,and no significant changes were found in the parameters mentioned above in NE group.Compared with E group,the serum ALT,AST,TNF-α and HMGB1 levels were significantly increased,and NLR2 mRNA and RIP2 expression was up-regulated in α-BGT group.The pathological changes in liver tissues were significantly reduced in group EA as compared with SS,NE and α-BGT groups.Conclusion Electro-acupuncture at Zusanli can reduce liver injury in a rat model of sepsis after scald and inhibition of NLR2/RIP2 signaling pathway and activation of cholinergic antiinflammatory pathway mediated by α7 nicotinic acetylcholine receptors in liver tissues may be involved in the mechanism.

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Comparison of blood high mobility group box-1 versus N-terminal prohormone of brain natriuretic peptide concentrations for assessment of cardiac dysfunction inpatients with severe sepsis

Zhuojun DENG ; Chunhua ZHANG ; Xuan GUO ; Shimin DONG

Chinese Journal of Anesthesiology.2014;34(10):1252-1254. doi:10.3760/cma.j.issn.0254-1416.2014.10.026

Objective To compare the blood high mobility group box-1 (HMGB-l) versus N-terminal prohormone of brain natriuretic peptide (NT-proBNP) for assessment of cardiac dysfunction in the patients with severe sepsis.Methods Ninety-eight patients of both sexes,aged 18-75 yr,were divided into 3 groups according to left ventricular ejection fraction (LVEF):non-cardiac dysfunction group (LVEF ≥ 50 ％,n =43),mild cardiac dysfunction group (30％ ≤ LVEF ＜ 50％,n =41),and severe cardiac dysfunction group (LVEF ＜ 30％,n =14).Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was performed.Venous blood samples were obtained for determination of the concentrations of HMGB-1 and NT-proBNP.Days of hospitalization and the survival rates within 28 days after admission to hospital were recorded.Pearson correlation between blood HMGB-l,NT-proBNP concentrations and LVEF was analyzed.Results Compared with non-cardiac dysfunction group,LVEF was significantly decreased,APACHE Ⅱ score and blood HMGB-1 and NT-proBNP concentrations were increased,days of hospitalization were prolonged,and the survival rates were decreased in mild and severe cardiac dysfunction groups,and the changes in the parameters mentioned above were more obvious in severe cardiac dysfunction group.The correlation coefficient between blood HMGB-1 concentration and LVEF was -0.639 and between blood NT-proBNP concentration and LVEF was-0.521,showing significant difference.Conclusion Blood HMGB-1 concentration provides higher reliability than blood NT-proBNP concentration in assessing the degree of cardiac dysfunction in the patients with severe sepsis.

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Effects of exogenous hydrogen sulfide on mitochondrial function during focal cerebral ischemia in rats

Meng ZHANG ; Guofeng LI ; Haikun LUO ; Jianxin ZHANG

Chinese Journal of Anesthesiology.2014;34(10):1259-1262. doi:10.3760/cma.j.issn.0254-1416.2014.10.028

Objective To investigate the effects of exogenous hydrogen sulfide (H2S) on the mitochondrial function during focal cerebral ischemia and the relationship with mitochondrial damage in rats.Methods Eighty male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 5 groups (n =16 each):sham operation group (group S),cerebral ischemia group (group CI),and high,medium and low dose NaHS groups (NaHS1,NaHS2 and NaHS3 groups).The animals were anesthetized with intraperitoneal chloral hydrate.The focal cerebral ischemia was induced by middle cerebral artery occlusion.Normal saline 1 ml/kg was injected intraperitoneally at 3 h after the model was established.NaHS 2.8,1.4 and 0.7 mg/kg were injected intraperitoneally in NaHS1,NaHS2 and NaHS3 groups,respectively.At 24 h after the model was established,the cerebral infarct volume was determined.The changes in the cerebral infarct volume were observed after administration of NaHS.Cerebral specimens on the ischemic side were obtained for determination of the content of H2S and activity of 3-mercaptopyruvate sulphurtransferase (3MST) in brain tissues.The mitochondria were extracted for determination of the activity and swelling of mitochondrial membrane and changes in the total ATPase,superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) content.Results Compared with group S,the cerebral infarct volume was significantly enlarged in CI,NaHS1,NaHS2 and NaHS3 groups,the content of H2 S in brain tissues and activity of mitochondrial 3MST were decreased in CI,NaHS2 and NaHS3 groups,the activities of mitochondria,SOD and GSH-Px were significantly decreased,and the swelling of mitochondrial membrane and content of MDA were increased in CI and NaHS3 groups,the total ATPase activity was decreased in CI group,and SOD activity was decreased in NaHS1 and NaHS2 groups.Compared with CI group,the cerebral infarct volume was significantly reduced,the content of H2 S in brain tissues and activity of mitochondrial 3MST were increased,the activities of mitochondria,total ATPase,SOD and GSH-Px were increased,the swelling of mitochondrial membrane was reduced,and the content of MDA was decreased in NaHS1 and NaHS2 groups.Conclusion The mechanism by which exogenous H2 S mitigates focal cerebral ischemia is related to enhanced anti-oxidant activity of mitochondria and reduced mitochondrial damage in rats.

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Effects of sevoflurane preconditioning on zonula occludens-1 during myocardial ischemia-reperfusion in rats in vitro

Huanhuan TIAN ; Qian DENG ; Yunting PANG ; Ganlin DENG ; Jindong LIU

Chinese Journal of Anesthesiology.2014;34(10):1263-1266. doi:10.3760/cma.j.issn.0254-1416.2014.10.029

Objective To evaluate the effects of sevoflurane preconditioning on zonula occludens-1 (ZO-1) during myocardial ischemia-reperfusion (I/R) in rats in vitro.Methods Adult male Wistar rats,weighing 250-300 g,were anesthetized with intraperitoneal pentobarbital 30 mg/kg and heparinized.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃.Eighteen isolated rat hearts were randomly assigned into 3 groups (n =6 each) using a random number table:control group (group C),group I/R and sevoflurane preconditioning group (group S).At 10 min of equilibration,the hearts were perfused with K-H solution for 110 min in group C,the hearts were perfused with K-H solution for 20 min,and then subjected to 30 min of ischemia followed by 60 min of reperfusion in group I/R,and the hearts were perfused with K-H solution saturated with 3％ sevoflurane for 15 min followed by 5 min washout,and then subjected to 30 min of ischemia followed by 60 min of reperfusion in group S.At the end of equilibration,immediately before ischemia,and at 15 and 60 min of reperfusion (T1,2),HR,left ventricular end-diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),+ dp/dtmax and-dp/dtmax were recorded.The development of arrhythmias was recorded during reperfusion and scored.At 60 min of reperfusion,myocardial specimens were obtained from the apex of heart for determination of the expression of ZO-1 in myocardial tissues (by Western blot) and for observation of distribution of ZO-1 and connexin43 (Cx43) (by immunofluorescence).Results Compared with group C,HR,LVDP,+ dp/dtmax and-dp/dtmax were significantly decreased and LVEDP was increased at 15 and 60 min of reperfusion,scores of arrhythmia was increased,and ZO-1 expression was down-regulated in I/R group.Compared with group I/R,HR,LVDP,+ dp/dtmax and-dp/dtmax were significantly increased and LVEDP was decreased at 15 and 60 min of reperfusion,arrhythmia was decreased,and ZO-1 expression was up-regulated in group S.ZO-1 and Cx43 were co-localized at the intercalated disk.ZO-1 was redistributed in the lateralization of the membrane and co-localized with Cx43 in group I/R.The incidence of ZO-1 lateralization was significantly decreased in group S.Conclusion The mechanism by which sevoflurane preconditioning decreases reperfusion arrhythmia is related to inhibition of down-regulation of expression and redistribution of ZO-1 and inhibition of redistribution of Cx43 in rats.

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Effects of dexmedetomidine on the cellular immune function of rats with scald

Xianjie WEN ; Hua LIANG ; Yuanying LIU ; Jiying ZHONG ; Hongzhen LIU ; Hanbing WANG ; Chengxiang YANG

Chinese Journal of Anesthesiology.2014;34(10):1267-1270. doi:10.3760/cma.j.issn.0254-1416.2014.10.030

Objective To evaluate the effects of dexmedetomidine on the cellular immune function of the rats with scald.Methods Seventy-two healthy male Sprague-Dawley rats,weighing 200-220 g,aged 120-150 days,were randomly divided into 3 groups (n =24 each):normal control group (group C),scald group (group S) and dexmedetomidine group (group D).Thirty percent of the total body surface was shaved and then exposed to 94 ℃ water for 12 s in S and D groups.The rats were resuscitated according to Parkland formula after scald in S and D groups,and in addition,dexmedetomidine 30 μg/kg was also intraperitoneally injected immediately after scald in D group.Before the model was established (T1) and at 12 and 24 h after scald (T2,3),blood samples from the inferior vena cava were collected for determination of T lymphocyte subsets CD3 +,CD4 + and CD8 +,NK cell,C-reactive protein (CRP),interleukin-6 (IL-6),IL-10 and tumor necrosis factor-alpha (TNF-α) level.CD4+/CD8+ was calculated.Arterial blood samples were collected for blood gas analysis.Results Compared with C,the CD3+,CD4+ and NK cell levels,CD4+/CD8+,pH value,PaCO2 and PaO2 were significantly decreased,and CD8+ levels,IL-6,IL-10,TNF-α,CRP and BE negative value were increased at T2,3 in S and D groups.Compared with group S,the CD3+,CD4+,NK cell and IL-10 levels,CD4+/CD8+,pH value,PaCO2 and PaO2 were significantly increased,and CD8+ levels,IL-6,TNF-α,CRP and BE negative value were decreased at T2,3 in group D.Conclusion Dexmedetomidine can improve the cellular immune function of the rats with scald.

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Effects of serum in patients with obstructive jaundice on proliferation, migration and phenotype modulation of human pulmonary arterial smooth muscle cells

Yong YANG ; Bing CHEN ; Yang CHEN ; Baoli ZU ; Bin YI ; Kaizhi LU

Chinese Journal of Anesthesiology.2014;34(10):1271-1274. doi:10.3760/cma.j.issn.0254-1416.2014.10.031

Objective To evaluate the effects of the serum in the patients with obstructive jaundice on the proliferation,migration and phenotype modulation of human pulmonary arterial smooth muscle cells (PASMCs).Methods PASMCs were isolated from the patients,underwent passage and were then subcultured.The cultured PASMCs were incubated with the serum in the patients with obstructive jaundice or with the serum in the healthy volunteers.At 24,48 and 72 h of incubation,the proliferation and migration of the cells were determined by CCK-8 assay and wound healing assay,respectively,and Western blot analysis was used for detection of smooth muscleα-actin (SM-α-actin) and calponin protein expression in human PASMCs.Results The proliferation and migration of human PASMCs were significantly enhanced,calponin protein expression was up-regulated at 24 h of incubation,and the SM-α-actin and calponin protein expression was down-regulated at 48 and 72 h of incubation when human PASMCs were incubated with the serum in the patients with obstructive jaundice as compared with those when the cells were incubated with the serum in the healthy volunteers.When human PASMCs were incubated with the serum in the patients with obstructive jaundice,the proliferation and migration of the cells were significantly enhanced,SM-α-actin expression was up-regulated and calponin protein expression was down-regulated at 48 h of incubation as compared with those at 24 h of incubation.When human PASMCs were incubated with the serum in the patients with obstructive jaundice,the migration of the cells was significantly enhanced,and no significant change was found in the proliferation and SM-α-actin and calponin protein expression at 72 h of incubation as compared with those at 48 h of incubation.Conclusion The serum in the patients with obstructive jaundice can enhance the proliferation and migration of human PASMCs and promotes synthetic PASMC phenotype.

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Effect of methylprednisolone on hepatic ischemia-reperfusion injury in patients undergoing hepatolobectomy

Tao ZHANG ; Liting KUANG ; Wenqi HUANG ; Yi MA ; Lu YANG

Chinese Journal of Anesthesiology.2014;34(11):1300-1302. doi:10.3760/cma.j.issn.0254-1416.2014.11.003

Objective To evaluate the effect of methylprednisolone on hepatic ischemia-reperfusion (I/R) injury in the patients undergoing hepatolobectomy.Methods Sixty ASA physical status Ⅱ or Ⅲ patients,aged 30-64 yr,weighing 45-75 kg,scheduled for elective hepatolobectomy,were randomized to control group or methylprednisolone group (n =30 each).After induction of anesthesia,methylprednisolone 500 mg (in 100 ml of normal saline) was infused intravenously at 5 ml/min before skin incision in group M.Anesthesia was induced with propofol,fentanyl and cisatracurium.The patients were endotracheally intubated and mechanically ventilated.PETCO2 was maintained at 35-45 mmHg.Anesthesia was maintained with 1％-3％ sevoflurane inhalation,remifentanil infusion,and intermittent iv boluses of fentanyl and cisatracurium.MAP was maintained at 70-100 mmHg and HR at 50-90 bpm.At 10 min before induction of anesthesia,and on postoperative day 1,3 and 5,venous blood samples were collected for determination of the plasma levels of alanine aminotransferase (ALT),aspartate amminotransferase (AST),total bilirubin (TBIL),tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).Results Compared with group C,the plasma levels of ALT,AST and TBIL were significantly decreased on postoperative day l and 3,and the plasma concentrations of TNF-α and IL-6 were decreased on postoperative day 1,3 and 5 in group M.Conclusion Methylprednisolone can reduce hepatic I/R injury in the patients undergoing hepatolobectomy and inhibition of systemic inflammatory responses is involved in the mechanism.

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Effects of dexmedetomidine on postoperative cognitive function in aged patients undergoing carotid endarterectomy

Yali GE ; Fengyun LONG ; Fang GUO ; Xiangzhi FANG ; Ju GAO

Chinese Journal of Anesthesiology.2014;34(11):1303-1305. doi:10.3760/cma.j.issn.0254-1416.2014.11.004

Objective To evaluate the effects of dexmedetomidine on postoperative cognitive function in the aged patients undergoing carotid endarterectomy.Methods Forty patients,aged 65-80 yr,of ASA physical status Ⅱ or Ⅲ,scheduled for elective carotid endarterectomy,were randomly divided into 2 groups (n =20 each):control group (group C) and dexmedetomidine group (group DEX).Anesthesia was induced with midazolam,etomidate,fentanyl and rocuronium.The patients were tracheally intubated.In group DEX,a loading dose of dexmedetomidine 0.03 μg· kg-1 ·min-1 was infused intravenously for 10 min starting from the time point before induction,and dexmedetomidine 0.30μg· kg-1 ·min-1 was infused until 30 min before the end of operation starting from the end of intubation.The equal volume of normal saline was given instead of dexmedetomidine in group C.At 1 day before operation (To) and 6 and 24 h after operation (T1.2),venous blood samples were collected for determination of serum brain-derived neurotrophic factor (BDNF) concentrations.The cognitive function of the patients was assessed using Mini-Mental State Examination (MMSE) at To,T2,and 48 h,72 h,7days and 1 month after operation (T3-6).Results Compared with the baseline value at T0,the serum BDNFconcentrations were significantly increased at T1 in the two groups,MMSE scores were decreased at T2,3 in groupC,and MMSE scores were decreased,and the serum BDNF concentrations were increased at T2 in group DEX.Compared with group C,the MMSE scores were significantly increased at T3.4,the serum BDNF concentrations were increased at T2,and no significant change was found in MMSE scores at T5.6 in group DEX.Conclusion Dexmedetomidine is helpful in improving postoperative cognitive function and in promoting the recovery of postoperative cognitive function,and the mechanism may be related to enhanced production of endogenous BDNF in the aged patients undergoing carotid endarterectomy.

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Effect of sevoflurane preconditioning on intestinal injury in patients undergoing resection for liver cancer

Meiliang WEI ; Xu CHEN ; Jianchun YUAN

Chinese Journal of Anesthesiology.2014;34(11):1306-1308. doi:10.3760/cma.j.issn.0254-1416.2014.11.005

Objective To evaluate the effect of sevoflurane preconditioning on intestinal injury in the patients undergoing resection for liver cancer.Methods Forty patients of both sexes,aged 20-60 yr,weighing 5075 kg,of ASA physical status Ⅱ or Ⅲ (liver function Child-Pugh grade A),undergoing resection for right liver cancer,were randomly divided into 2 groups (n =20 each):sevoflurane preconditioning group (S group) and control group (C group).Anesthesia was induced with target-controlled infusion of propofol and remifentanil.Tracheal intubation was facilitated with cisatracurium.Anesthesia was maintained with target-controlled infusion of propofol and remifentanil.S group inhaled sevoflurane with the end-tidal concentration of 2.0％ for 30 min starting from the end of intubation,followed by washout.Before induction (T0),immediately after hepatic portal was clamped (T1),at 1,3 and 6 h after occlusion of hepatic portal was released (T2-4) and at 24 h after operation (T5),arterial blood samples were obtained for determination of serum tumor necrosis factor-alpha (TNF-α),intestinal fatty acids binding protein (Ⅰ-FABP) and D-lactate levels.Results The concentrations of serum TNF-α and D-lactate started to rise at T2,peaked at T4,and started to decline at T5,and the serum Ⅰ-FABP concentrations started to rise at T2,peaked at T3,and started to decline at T4 in the two groups.The concentrations of serum TNF-α,Ⅰ-FABP and D-lactate were significantly lower in S group than in C group.Conclusion Sevoflurane preconditioning can inhibit inflammatory responses and reduce intestinal injury in the patients undergoing resection for liver cancer.

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