Surfactin inhibits Fusarium graminearum by accumulating intracellular ROS and inducing apoptosis mechanisms.

Fusarium graminearum, a devastating fungal pathogen, is the main pathogen of Fusarium head blight (FHB) in wheat globally; it results in significant yield loss and mycotoxin contamination that severely threatens global wheat production and food safety. However, despite ongoing efforts, controlling this pathogen still remains a major challenge. Surfactin, primarily synthesized by Bacillus sp. via non-ribosomal peptide synthetases, exhibits potent surfactant and antibacterial properties, but its antifungal mechanism has yet to be fully elucidated. We found that the EC50 of surfactin against hyphal growth of F. graminearum was 102.1 µg/mL, and control efficacy against wheat FHB under field conditions achieved 86.38% in wheat cultivar Huaimai 40 and 81.60% in wheat cultivar Zhoumai 36, indicating that surfactin has potential antifungal activity against F. graminearum. Accumulated intracellular ROS, decreased mitochondrial membrane potential (MMP), activated metacaspase activity and condensed chromatin, were induced by surfactin in F. graminearum hyphae, suggesting that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Furthermore, accumulated intracellular ROS was evidenced to act as a key mediator of surfactin-induced apoptosis. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that surfactin induces caspase-independent apoptosis in F. graminearum. Collectively, this study provides evidence that surfactin induces a ROS-mediated mitochondrial apoptosis in F. graminearum hyphae, and may exert its antifungal activity against F. graminearum by activating apoptosis. This study demonstrates the potential of surfactin as an antifungal agent for FHB biocontrol, provides a new perspective on the antifungal mechanism of surfactin against filamentous fungi, and contributes to the application of surfactin-producing microbes in the biocontrol of plant diseases.

Protective effects of valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement / 中国药房

OBJECTIVE To study the protective effects o f valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement. METHODS The rats were divided into scalding+delayed fluid replacement group （group S ），scalding+seawater immersion+delayed fluid replacement group （group SS ）， scalding+seawater immersion+valproic acid+delayed fluid replacement group （group SSV ）according to random number table ，with 60 rats in each group. All groups were subjected to 35％total body surface area third-degree full-thickness scalding with boiled water. Group SS and group SSV were immersed in artificial ；seawater（30 min）immediately after scalding ，and group SSV was subcutaneously injected with valproic acid 300 mg/kg immediately after out of water. Sodium lactate Ringer ’s 0314-2279277。E-mail：125467374@qq.com injection was injected intravenously within 30 minutes according to 1/2 Parkland formula at 2 h after scalding in each group for delayed fluid replacement. The death time of rats was recorded ，and the average survival time and 24 h survival rate of rats in each group were calculat ed. Mean arterial pressure （MAP），heart rate （HR），respiration rate （RR），rectal temperature （RT），arterial blood pH ，arterial partial pressure of oxygen （PaO2），arterial blood partial pressure of carbon dioxide （PaCO2），HCO3－，creatine kinase MB isoenzyme （CK-MB）and neuron specific enolase （NSE）were detected before scalding ，at 0，2，5 h after scalding. The pathological changes of cardiac and cerebral tissue were observed. RESULTS The 24 h survival rate of group SS （55％）was significantly lower than that of group S （90％）， while that of group SSV （75％）was increased significantly ，compared with group SS （P＜0.05）. Compared with group S ，the levels of MAP ，RT，HR，pH，PaO2 and HCO 3－ in group SS were significantly lowered ，while the levels of CK-MB and NSE were increased significantly at 0，2，5 h after scalding ；the levels of PaCO 2 were increased significantly at 2，5 h after scalding ， while the levels of RR were decreased significantly at 0，2 h after scalding （P＜0.05）. Compared with group SS ，the levels of MAP，RT，HR，pH，PaO2 and HCO 3－ in group SSV were significantly increased ，while the levels of PaCO 2，CK-MB and NSE were decreased significantly at 2，5 h after scalding ；the level of RR was increased significantly at 2 h after scalding （P＜0.05）. At 2，5 h after scalding ，cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S ；cardiac and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding combined seawater immersion injury ，hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats ， improve vital signs and blood gas index ，prolong survival time and improve survival rate in rats.

In vivo study of resveratrol regulating Wnt signaling pathway to enhance temozolomide against gliomas / 中华神经医学杂志

Objective To investigate the effect of resveratrol (Res) on temozolomide (TEM) against gliomas in vivo.Methods Human glioma cell line T98G was transplanted into BALB/C-nu female nude mice to establish orthotopic human glioma cell transplanted models.Five d after modeling,the 48 successfully modeled nude mice were randomly divided into solvent control group,Res group,TEM group,combination drug group,Wnt signaling pathway agonist group,and Wnt signaling pathway inhibitor group(n=8);and dimethyl sulfoxide (10 mg/kg),Res (10 mg/kg),TEM (25 mg/kg),Res (10mg/kg+TEM (25 mg/kg),Res (10 mg/kg)+TEM (25 mg/kg)+lithium chloride (2 mg/kg),and Res (10mg/kg)+TEM (25 mg/kg)+IWR-1 (5 mg/kg) were given,respectively,once/d for 30 d.During the administration,the survival status of nude mice in each group was continuously observed,tumor volume was measured by MR imaging every 5 d.Thirty d after administration,TUNEL was used to detect the apoptosis of tumor cells,and immunofluorescence was used to detect the immunofluorescent intensity of O6-methylguanine-DNA methyltransferase (MGMT) and β-catenin in the tumor tissues.Western blotting was used to detect the protein expression levels of Wnt signaling pathway-related proteins (Wnt2,and β-catenin),MGMT,and glycogen synthase kinase 3β (GSK3β).Results As compared with the TEM group,the combination drug group and Wnt signaling pathway inhibitor group had significantly decreased tumor volumes 20,25,30,and 35 d after modeling (/P＜0.05);as compared with the combination drug group,the Wnt signaling pathway inhibitor group had significantly decreased tumor volumes while Wnt signaling pathway agonist group had significantly increased tumor volumes 20,25,30,and 35 d after modeling (P＜0.05).TUNEL showed that the apoptosis rate of tumor cells in the combination drug group and Wnt signaling pathway inhibitor group was significantly increased as compared with that in the temozolomide group (P＜0.05);as compared with that in the TEM group,the apoptosis rate of tumor cells in the Wnt signaling pathway inhibitor group was significantly increased while that in the Wnt signaling pathway agonist group was statistically decreased (P＜0.05).Western blotting results showed that as compared with those in the combination drug group,the protein expression levels ofWnt2,β-catenin,and MGMT in the Wnt signaling pathway inhibitor group were significantly reduced,and GSK-3β protein expression level was significantly increased;while the protein expression levels of Wnt2,[β-catenin,and MGMT in the Wnt signaling pathway agonist group were significantly increased,and GSK-3β protein expression level was significantly decreased (P＜0.05).Conclusion Res inhibits Wnt signaling pathway by reducing expressions of Wnt2 and β-catenin,leading to decrease in MGMT expression,thereby enhancing the anti-glioma effect of TEM.

Cardioprotective effects of ulinastatin against isoproterenol-induced chronic heart failure through the PI3K­Akt, p38 MAPK and NF-κB pathways.

The purpose of the present study was to evaluate the cardioprotective effect of ulinastatin against isoproterenol­induced chronic heart failure (CHF). Compared with the control group, treatment with ulinastatin decreased interventricular septal thickness and left ventricular posterior wall thickness, and improved the left ventricular ejection fraction, left ventricular fractional shortening and peak E and peak A ratio in the isoproterenol­induced CHF rat. In addition, ulinastatin suppressed inflammation, oxidative stress and apoptosis in heart tissue from isoproterenol­induced CHF rats. Ulinastatin induced the activation of the phosphatidylinositol 3­kinase (PI3K)/RAC­α serine/threonine protein kinase (Akt) signaling pathway and downregulated the p38 mitogen­activated protein kinase (MAPK) and nuclear factor (NF)­κB pathway in isoproterenol­induced CHF rats. These data demonstrated the cardioprotective effect of ulinastatin against isoproterenol­induced chronic heart failure through the PI3K­Akt, p38 MAPK and NF­κB pathways.

Xuebijing Injection () increases early survival rate by alleviating pulmonary vasopermeability in rats subjected to severe burns / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Xuebijing Injection (, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury.</p><p><b>METHODS</b>Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflflammatory mediators in PMECs culture supernatant were also investigated.</p><p><b>RESULTS</b>The average survival time in the scald+XBJ group was 582.1±21.2 min, which was signifificantly longer than that in the scald + NS group (345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-α), E-selectin, interleukin-6 (IL-6), vascular permeability and water content of lung tissues were signifificantly increased in animals after severe burns (P<0.01). However, administration of XBJ signifificantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum (P<0.01).</p><p><b>CONCLUSIONS</b>XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.</p>

Protective effects of valproic acid on gut barrier function after major burn injury and its mechanism / 中华危重病急救医学

Objective To investigate the potential protective effects of valproic acid (VPA) on gut barrier function after major burn injury in rats and its mechanism.Methods Forty male Sprague-Dawley (SD) rats were divided into sham + normal saline (NS),sham + VPA,scald + NS,and scald + VPA groups,with 10 rats in each group.Rat with 55％ total body surface area (TBSA) third-degree severe-bums model was reproduced by immersing into 80 ℃ water,and the rats in sham groups were given sham-bums by immersing into 37 ℃ water.The rats after severebums were immediately treated with 0.25 mL of 300 mg/kg VPA or NS by subcutaneous injection.Rats were sacrificed at 2 hours and 6 hours after injury,and abdominal aortic blood and ileal tissue were harvested.The levels of vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA).The intestinal permeability was evaluated by fluorescein isothiocyanate-dextran (FITC-dextran) determination.The histomorphological changes in gut barrier were evaluated by Chiu grading system.Levels of acetylated lysine at the ninth position of histone 3 protein (Ac-H3K9),hypoxia-inducible factor 1α (HIF-1α),zona occludens 1 (ZO-1) and myosin light chain kinase (MLCK) were determined by immunofluorescence staining and Western Blot.Results Compared with sham + NS group,rats in scald + NS group showed intestinal mucosal damage 2 hours after bum injury,as well as increased mucosal permeability,protein expression levels of HIF-1 α,VEGF,MLCK,and lowered levels of AC-H3K9 and ZO-1.These changes were much more prominent at 6 hours after injury.VPA treatment significantly attenuated the bum-induced intestinal damage.Compared with scald + NS group,the protective effects in scald + VPA group was not evident at 2 hours after injury;however,intestinal damage was much less severe at 6 hours after injury (Chiu score:2.03 ± 0.27 vs.3.12 ± 0.15),intestinal permeability was significantly decreased [FITC-dextran (μg/L):709 ± 76 vs.1138 ± 75],histone acetylation was enhanced [Ac-H3K9 (gray value):1.55 ± 0.12 vs.0.48±0.12],ZO-1 degradation was significantly inhibited (gray value:0.69 ± 0.12 vs.0.43 ± 0.16),the protein expression levels of VEGF and MLCK were significantly down-regulated [VEGF (ng/mg):51.7±3.7 vs.71.2±4.3,MLCK (gray value):1.98±0.20 vs.2.80±0.24],while the HIF-1 α protein expression levels were significantly reduced at both 2 hours and 6 hours after injury (gray value:2.50±0.39 vs.3.88±0.42 at 2 hours,1.83±0.42 vs.4.42±0.41 at 6 hours,all P ＜ 0.05).Conclusions Severe bum injury can induce histone deacetylation,ZO-1 degradation and intestinal barrier dysfunction.VPA can improve the levels of histone acetylation and ZO-1,and protect intestinal epithelial barrier function.These may probably be mediated through inhibiting HIF-1α and its downstream gene VEGF and MLCK.

Regulating action of cyanidin-3-O-glucoside and cyanidin on osteoclast / 国际药学研究杂志

Cyanidin-3-O-glucoside is a kind of anthocyanin,which is one of the most abundant and widely available anthocya-nins in the world. The anthocyanidin part of it named cyanidin,without glucosidic group,is also widely available. A large number of epidemiological studies have shown that anthocyanins have the effect of preventing osteoporosis. Cyanidin-3-O-glucoside and its antho-cyanidin can inhibit the proliferation,differentiation and maturation of osteoclasts by NF-κβsignaling pathway,and inhibit the expres-sion of a variety of osteoclast markers,but its role in regulating NF-κβsignaling pathway and mechanism is not yet clear. This paper re-views the effects and mechanisms of cyanidin and cyanidin-3-O-glucoside on osteoclast,in hope of providing some research ideas for the prevention or treatment of osteoporosis.

Inhibitory effect of electro-acunpunture at Zusanli point on flammatory factors of postoperative intra-abdominal adhesions / 军事医学

Objective To observe the inhibitive effect of electro-acupuncture (EA)at Zusanli points (ST36)on inflammatory mediators of postoperative intra-abdominal adhesions and study the relationship between EA and cholinergic anti-inflammatory pathway.Methods Forty-eight male Wistar rats were divided into 6 groups (each =8):Group A (control),Group B(abdominal adhesions model),Group C (abdominal adhesions plus EA),Group D(sham acu-point control),Group E (abdominal adhesions plus α-bungarotoxin )and Group F (abdominal adhesions plus EA after α-bungarotoxin).Animal models of abdominal adhesion were produced by Chiang’s path.Bilateral Zusanli points (ST36) and shame acupoints were electro-acupunctured at a constant voltage for 1 hour while rats were awake.The ɑ-BGT(1 μg/kg)was injected into the abdominal cavity after surgery.All the rats were sacrificed on the 3rd day,and the levels of inflammatory mediators (TNF-ɑ,NO and NOS)in tissues were evaluated.Results Three days after surgery,the damaged cecum of abdominal adhesion groups developed obvious edema that did not adhere with other tissues.Compared with sham control,the abdominal adhesion resulted in significant elevation of inflammatory mediators (TNF-ɑ,NO and NOS).EA at Zusanli points obviously lowered the elevated levels of inflammatory mediators (P <0.01 and P <0.05).EA at Zusanli points following the injection of ɑ-BGT showed less anti-inflammatory effect(P <0.01).Conclusion EA at Zusanli points significantly lowers the elevated levels of inflammatory mediators after abdominal adhesion challenge.The activation of cholinergic anti-inflammatory pathway might be one of the mechanisms by which Zusanli points exert anti-inflammatory effects.

Effects of electroacupuncture at Zusanli points on gut permeability in rats with intestinal ischemia/reperfusion injury / 中国中西医结合急救杂志

Objective To investigate the protective effects of elctroacupuncture(EA)at Zusanli(ST36) points on intestinal villas damage and mucosal permeability induced by small intestine pro-inflammatory factors in rats with intestinal ischemia/reperfusion(I/R). Methods 30 Sprague-Dawley(SD)rats were randomly divided into three groups(each,n=10):intestinal I/R group(model group),intestinal I/R+EA ST36 group(EA group)and intestinal I/R+sham EA group(SEA group). Rats were subjected to superior mesenteric artery(SMA)clamping at its root part to occlude the vessel for 30 minutes,followed by reperfusion for 60 minutes to form intestinal I/R models. Rats in EA group received EA at the bilateral ST36 points(2-3 mA,2-100 Hz)for 30 minutes immediately after ischemia,those in SEA group received EA at bilateral sham points(the point was located at 0.5 cm away from ST36 point in its lateral side)with the same frequency and intensity of stimulation as EA group for 30 minutes,and those in model group received no treatment. Animals were sacrificed 60 minutes after reperfusion and segments of distal part of ileum were harvested,then the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in intestinal tissue were measured. Histopathologic changes were viewed and graded via light microscopy. A solution of fluorescein isothiocyanate(FITC)-dextran was injected into the lumen of the segment of intestine 30 minutes after reperfusion,systemic blood was drawn via abdominal aorta puncture at 60 minutes after reperfusion,and then the level of FITC-dextran in blood was measured to determine the changes in intestinal permeability. Results Compared to the model group and SEA group,EA ST36 significantly attenuated intestine TNF-α(pg/mg:3.01±0.50 vs. 8.65±1.02,8.42±1.41,both P0.05). Sections of distal ileum from animals in the model group and SEA group showed no obvious difference histologically,and the pathological manifestations were villous tip necrosis, blunt-shaped and collapse. Compared to the model group and SEA group,the intestinal villous injury in animals of EA group was much milder. Conclusion In rats with intestinal I/R injury,EA ST36 points has protective effect on the gut that is possibly due to the fact it may obviously lower the levels of the pro-inflammatory factors of small intestinal tissue,alleviate mucosal insult of gut and reduce the mucosal permeability.

Effect of Pyruvate-enriched ORS on intestinal mucosal blood flow, activity of Na+-K+-ATPase and intesti-nal absorption rate during enteral resuscitation of scalded rats / 医学研究生学报

Objective Gastrointestinal rehydration is a simple and effective method in treatment of burn shock during war-time, fire disaster and other harsh conditions , and practice has proved the exact curative effect of HCO 3 salt sugar liquid .This article was to investigate the effect of pyruvate-enriched oral rehydration solution ( Pyr-ORS ) on intestinal mucosal blood flow ( IMBF ) , activity of Na +-K+-ATPase and intestinal absorption rate during en-teral resuscitation of a 35% TBSA third-degree scald in rats . Methods 90 male rats were randomly divided into 5 groups: scald without fluid resuscitation ( S group ); sham scald resuscitated with HCO3 salt sugar liquid ( SS HCO3 group ); sham scald resuscitated with Pyr-ORS ( SS Pyr-ORS group ); scald resuscitated with HCO 3 salt sugar liquid (S HCO3 group); scald resuscitated with Pyr-ORS (S Pyr-ORS group) (n=18).Each group was divided into 2 subgroups of 1.5 and 4.5 h after scald injury.Intestinal absorption rate of water and Na +, IMBF and activity of Na +-K+-ATPase were detected on each group . Results Compared with shame scald groups , the intestinal absorption rates of water and Na +decreased ob-viously in scald groups with fluid resuscitation (P<0.05);at 1 h after scald injury, the intestinal absorption rates of water and Na +in S Pyr-ORS groups were both higher than those in S HCO 3 groups(P<0.05).Compared with shame scald groups , IMBF and activity of Na+-K+-ATPase at 1.5 and 4.5 h after scald injury decreased obviously in scald groups with fluid resuscitation (P<0.05); at 1.5 and 4.5 h after scald injury, IMBF in S Pyr-ORS groups (95.250 ±5.096/112.765 ±7.215) were greater than those in S HCO3 group (80.764 ±7.852/94.671 ±8.469), which was of statistical significance (P<0.05). Conclusion Pyr-ORS is a simple and effec-tive method in treatment of burn shock during wartime , fire disaster and other harsh conditions .

The effects of sodium pyruvate Ringer solution on hemodynamic and organ functions during shock stage in dogs with a 50％ total body surface area full-thickness burn / 中华危重病急救医学

Objective To compare the effect of intravenous resuscitation with sodium pyruvate (Pyr) Ringer solution against lactated Ringer solution on hemodynamic and organ functions during shock stage in dogs with burn.Methods 28 Beagle dogs were subjected to 50％ total body surface area (TBSA) burn,and they were divided into three groups:burn injury without fluid resuscitation (N R,n =8),Ringer lactate solution(RL,n =10),and Pyr Ringer solution (RP,n =10).They were given intravenous fluid resuscitation according to Parkland formula 30 minutes after burn.The hemodynamics,organ functions and mortality were observed in conscious state before burn injury,and 2,6,8,12,24 hours after burn injury.Results Within 24 hours after burn,all the dogs in NR group died,and those in RL and RP groups were all alive.At 2 hours after burn,the mean arterial pressure (MAP),cardiac index (CI),dp/dt max of left ventricular contractility were significantly reduced in NR,RL and RP groups compared with those before injury [MAP(mmHg,1 mmHg =0.133 kPa):45.33 ± 7.78 vs.141.67 ± 5.98,91.33 ± 10.25 vs.142.33 ± 6.16,98.67 ± 9.54 vs.142.83 ±5.47; CI (mL·s-1·m-2):8.17 ±0.83 vs.48.34 ±3.33,16.84 ±2.17 vs.47.34 ± 1.67,19.00 ± 1.50 vs.47.34 ± 1.33; dp/dt max (mmHg/s):426.83 ± 51.91 vs.1 372.50 ± 39.61,594.00 ± 88.23 vs.1 363.83 ± 44.92,645.00 ±66.82 vs.1 395.83 ± 19.49,all P＜0.05],and the systemic vascular resistance (SVR) and alanine transaminase (ALT),creatinine (Cr),serum MB isoenzyme of creatine kinase (CK-MB),diamine oxidase (DAO) were significantly higher [SVR (kPa·s ·L-1):1 322.50 ±36.37 vs.281.45 ± 8.84,777.50 ±41.84 vs.289.72 ± 6.70,571.40 ±40.01 vs.286.27 ±8.66; ALT (U/L):89.50 ±4.11 vs.40.57 ±3.63,89.25 ±4.88 vs.37.92 ± 2.62,86.30 ±5.61 vs.38.47 ±3.50; Cr (μmol/L):75.62 ±4.61 vs.41.58 ±2.78,77.00 ±5.92 vs.46.55 ± 3.17,74.13 ±2.56 vs.45.65 ± 1.83; CK-MB (kU/L):13.122 ±0.282 vs.1.557 ±0.009,8.885 ±0.272 vs.1.497 ± 0.009,8.692 ± 0.180 vs.1.490 ± 0.005; DAO (kU/L):2.26 ± 0.14 vs.0.25 ± 0.02,1.50 ± 0.07 vs.0.25 ± 0.01,1.37 ± 0.07 vs.0.25 ± 0.02,all P＜0.05].All parameters in NR group kept on worsening till death,while hemodynamic and organ functions of two intravenous resuscitation groups were gradually improved,CI,SVR and DAO in RP group were significantly superior to those of RL group from 2 hours on after burn (all P＜0.05),and dp/dt max and CK-MB in RP group were significantly better than those of RL group from 6 hours on after burn [dp/dt max (mmHg/s):1 082.33 ± 63.59 vs.1 018.60 ± 47.36,CK-MB (U/L):7 898.70 ± 255.74 vs.8 438.70 ± 442.00,all P＜0.05],and MAP (mmHg) was significantly better than that of RL group at 6 hours (124.67 ± 9.39 vs.114.33 ± 9.16,P＜0.05),and Cr (tμmol/L) was significantly better than that of RL group from 24 hours on after burn (53.42 ± 4.99 vs.60.77 ± 3.11,P＜0.05).Conclusion The Pyr Ringer solution was superior to the Ringer lactate solution in improving hemodynamic and organ functions for intravenous resuscitation in dogs with 50％TBSA full thickness burn.

Effects of oral pyruvate-glucose-electrolyte solution on organ function and survival in resuscitation of lethal hemorrhagic shock rats / 中华急诊医学杂志

Objective To study the effects of oral rehydration with the solution of pyruvate-glucoseelectrolyte (PGES) by comparison with the bicarbonate-glucose-electrolyte solution (BGES) on resuscitation in rats with lethal hemorrhagic shock.Methods Sixty adult male SD rats with intra-gastric tube,and cannulation of femoral artery and vein were subjected to 45％ total blood volume loss from the femoral artery,and then randomly divided into three groups (n =20 in each group):no fluid resuscitation group (NR),oral fluid resuscitation with the PGES group (PGES) and oral fluid resuscitation with the BGES group (BGES).In NR group,the animals received no fluid replacement or any other treatment.Rats in PGES and BGES groups were infused intra-gastrically with pre-warmed PGES or BGES in volume of 2 times shed blood given at 30 min after hemorrhage and completed within 6 hours.Blood samples in each group were collected from the abdominal aorta before or at 0,1,2,4 h post hemorrhage to detect serum alanine aminotransferase (ALT),creatinine (Cr),creatine phosphate kinase isoenzyme (CK-MB) and intestinal fatty acid binding protein (iFABP).Another 84 rats randomly divided into four groups:NR group (n =24),PGES group (n =24),BGES group (n =24),and no hemorrhage group (NH group,n =12).Rats in the three hemorrhage groups were treated the same as described above,and the rats in NH group underwent the same surgical procedure without hemorrhage were served as the sham group.All these rats were observed for their 24-hour survival rates.Results The 24-hour survival rates of PGES and BGES groups were both significantly higher than the rate of NR group (11/24 vs.1/24,x2 =18.087,P ＜0.01 ; 5/24 vs.1/24,x2 =6.445,P ＜ 0.05) ; the survival rate of PGES group was also significantly higher than that of BGES group (11/24 vs.5/24,x2 =4.02,P ＜ 0.05).All levels of ALT,CK-MB,Cr and iFABP in both the NR group and two oral resuscitation groups at 1 h,2 h and 4 h post hemorrhage were significantly higher than those before the blood loss,respectively (P ＜ 0.01).These biomarkers at 2 h,4 h post hemorrhage were significantly lower in the PGES and BGES groups than those in NR group (P ＜ 0.01) ; the serum levels of ALT,CK-MB,Cr and iFABP were significantly lower in the PGES group than those in the BGES group at 2 h and 4 h post hemorrhage,respectively (P ＜ 0.05).Conclusions Present results demonstrated that the pyruvate-enriched oral re-hydration solution (ORS =PGES) was more effective in preserving the organ function and prolonging the animal survival after resuscitation of lethal hemorrhagic shock in comparison with the bicarbonate-containing ORS (BGES).The oral re-hydration solution (PGES) recommended by the World Hygiene Organization (WHO ORS) may require further improvement in oral resuscitation of shock and the PGES may be recommended as a choice of oral re-hydration salts in the treatment of lethal hemorrhagic shock when intravenous administration is not available.

Effects of oral fluid resuscitation with pyruvate-oral rehydration solution on the hemodynamic parameters and organ functions during shock stage in dogs with a 50% total body surface area full thickness burn / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effect of oral fluid resuscitation with pyruvate sodium-glucose-electrolyte solution (PGES) on hemodynamics, organ functions and mortalities during shock stage in dogs with burn.</p><p><b>METHODS</b>In comparison of oral pyruvate sodium-glucose-electrolyte solution (PGES) with NaHCO₃-glucose-electrolyte solution (HGES), beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 hours were subjected to a 50% total body surface area (TBSA) burn, and were divided into three groups: pure burn without fluid resuscitation (NR, n = 8), and two oral fluid resuscitation (each n = 10), in which dogs were given with Pry-GES (OP) or NaHCO₃-GES (OH) according to Parkland formula. The hemodynamic and organ functions were measured serially before burn and 2, 6, 8, 12 and 24 hours after burn at no anaesthesia state A. Twenty-four hours mortality rate following burn was also recorded.</p><p><b>RESULTS</b>Two hours after burn, the mean arterial pressure of NR, OH and OP group was (45 ± 8), (57 ± 8) and (80 ± 9) mmHg (1 mmHg = 0.133 kPa) respectively, which were significantly reduced (t = 16.967, 14.595 and 10.100, all P < 0.05) compared with those before injury ((42 ± 6), (144 ± 6) and (142 ± 6) mmHg respectively), the change of cardiac output, dp/dtmax of left ventricular contractility and intestinal mucosal blood flow had the same trend as the mean arterial pressure. The systemic vascular resistance and organ parameters (Cr, CK-MB, ALT and DAO) in all groups increased obviously (t = -46.894--2.465, all P < 0.05). All measurements of NR group kept worsening, and all died within 24 hours after burn; while those of two oral resuscitation groups had improved gradually (F = 0.001-1.600, all P < 0.05), OP group was significantly superior to OH group (F = 0.013-0.466, P < 0.05). At 24 hours after burn, 6 (6/10) survived in OP group, 4 (4/10) in OH group and 0 (0/8) in NR group.</p><p><b>CONCLUSION</b>The Pyr-GES may be superior to the standard NaHCO₃-GES in the improvement of hemodynamics and organ functions during oral resuscitation in dogs with 50%TBSA full thickness burn.</p>

Effect of electroacupuncture on inflammatory injury induced by intestinal ischemia/reperfusion in rats / 中国针灸

<p><b>OBJECTIVE</b>To observe the protective effect of electroacupuncture (EA) at "Zusanli" (ST 36) on inflammatory injury induced by intestinal ischemia/reperfusion (I/R) in rats.</p><p><b>METHODS</b>Forty-eight Wistar rats were randomly divided into a sham injury group, a model group, an EA group and a sham EA group, 12 rats in each group. Intestinal I/R rat models were established by method of clamping with occlusion of superior mesenteric artery (SMA) for 45 min followed by reperfusion. The EA group was treated with EA (2.5 mA, 2 Hz/100 Hz, 0.5 h) at "Zusanli" (ST 36) 30 min before reperfusion, and at the same time, the sham EA group was treated with fast insertion at two non-meridian acupoints on skin surface (2 cm horizontally away from linea alba abdominis and about 5 cm paralleled to cartilago ensiformis downward). No interventions were added on the sham injury group and the model group. The degree of pathological injury in intestines, water rate of intestines, diamine oxidase (DAO) activity and intestinal mucosal blood flow (IMBF) were examined at 1 h and 3 h after reperfusion.</p><p><b>RESULTS</b>At 1 h and 3 h after reperfusion, the intestinal pathological injury in EA group was significantly attenuated compared with that in model group, and the intestinal water rate of (74.00 +/- 2.11)% and (78.78 +/- 0.80)% in EA group were significantly lower than (80.69 +/- 1.66)% and (83.17 +/- 2.08)% in model group (both P < 0.01), but DAO of (68.83 +/- 4.31) U/L and (47.84 +/- 5.57) U/L as well as IMBF of (152 +/- 5.8) PU and (139.8 +/- 6.1) PU in EA group were significantly higher than DAO of (32.86 +/- 4.72) U/L, (17.01 +/- 2.96) U/L as well as IMBF of (124.7 +/- 8.3) PU and (89.4 +/- 13.2) PU in model group (all P < 0.01). Meanwhile, the above mentioned changes in sham EA group showed no significant differences compared with those in model group (all P > 0.05).</p><p><b>CONCLUSION</b>Electroacupuncture can not only reduce the inflammatory injury induced by intestinal IR but also increase intestinal blood supply so as to protect the intestine function.</p>

The effects of delayed fluid resuscitation on hemodynamics and visceral perfusion in dogs with hemorrhagic shock / 中华急诊医学杂志

Objective To investigate the effects of delayed fluid resuscitation on hemodynamics and visceral perfusion in dogs with hemorrhagic shock. Methods Fourteen Beagle dogs were prepared for cannulation of carotid artery and jugular vein, and 24 hours later they were subjected to hemorrhagic shock with about 42% of total blood volume exsanguinated. Animals were divided into delayed resuscitation group ( DR group, n = 8) and immediate resuscitation group ( IR group, n = 6) . In the first 24 hours after hemorrhage, dogs in Dr group were given no fluid resuscitation, while those in IR group were immediately given resuscitation with intra-venous glucose-electrolyte solution, of which the volume was three times that of blood loss. In the second 24 hours, all animals had intra-venous fluid resuscitation. The variables of hemodynamics and visceral perfusion were determined before hemorrhage and 2, 4, 8, 24, 48 and 72 hours after hemorrhage under conscious state of dogs. Results After hemorrhage, the mean arterial pressure,cardiac output index, max of left ventricular contractility, blood flow of intestinal mucosa and urinary output greatly decreased and systemic vascular resistance obviously increased in each group compared with those before hemorrhage ( P ＜ 0.05 ) . From 4 hours after hemorrhage, the above measurements of dogs in IR group gradually resumed and reach Oh levels in 72 hours after hemorrhage except systemic vascular resistance index and intestinal blood flow. Whereas those measurements in dogs of DR group kept on worsening, and the levels of mean arterial pressure, cardiac output index, intestinal blood flow and urinary output were significantly lower than those in dogs of IR group ( P ＜ 0. 05 ) . Over 72 hours, five of eight dogs died with anuria in DR, and no animals died in IR group. Conclusion The findings indicate that delayed fluid resuscitation deteriorates hemodynamics, handicapping the restoration of visceral perfusion and increasing mortality in dogs with hemorrhagic shock.

SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic (DAergic) neurons for Parkinson's disease (PD) research and to determine the effect of differentiation on this cell model.</p><p><b>DATA SOURCES</b>The data of this review were selected from the original reports and reviews related to SH-SY5Y cells published in Chinese and foreign journals (Pubmed 1973 to 2009).</p><p><b>STUDY SELECTION</b>After searching the literature, 60 articles were selected to address this review.</p><p><b>RESULTS</b>The SH-SY5Y cell line has become a popular cell model for PD research because this cell line posses many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-beta-hydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained. However, different differentiating agents induce different neuronal phenotypes and biochemical changes. For example, retinoic acid induces differentiation toward a cholinergic neuronal phenotype and increases the susceptibility of SH-SY5Y cells to neurotoxins and neuroprotective agents, whereas treatment with retinoic acid followed by phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in a DAergic neuronal phenotype and decreases the susceptibility of cells to neurotoxins and neuroprotective agents. Some differentiating agents also alter kinetics of 1-methyl-4-phenyl-pyridinium (MPP(+)) uptake, making SH-SY5Y cells more similar to primary mesencephalic neurons.</p><p><b>CONCLUSIONS</b>Differentiated and undifferentiated SH-SY5Y cells have been widely used as a cell model of DAergic neurons for PD research. Some differentiating agents afford SH-SY5Y cells with more potential for studying neurotoxicity and neuroprotection and are thus more relevant to experimental PD research.</p>

Carbachol improve oxygen dynamic parameters during orally fluid resuscitation of a 50% TBSA full-thickness burn in dogs / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of carbachol(CAR) on oxygen dynamic parameters and hyperlactacidemia during oral fluid resuscitation of burn shock.</p><p><b>METHODS</b>Twelve male Beagle dogs were surgically prepared for cannulation of carotid and jugular vein, and enterostomy, 24 hours later they were subjected to a 50% (total body surface area, TBSA) full-thickness flame injury under a 10-15 minute anesthesia by IV injection of propofol. The dogs were randomized to gastric fluid infusion group (GI group)and gastric fluid infusion plus CAR group (GI + CAR). Either a glucose-electrolyte solution(GES) or GES containing CAR (20 microg/kg) were intragastricly given to animals in GI group or GI+ CAR groups. The delivery rate and volume of GES was in accordance with that of Parkland formula. Mean arterial pressure (MAP), intestinal mucosal blood flow (IMBF) and blood lactic acid were determined, and blood gas analysis evaluated for oxygen delivery (DO2), oxygen consumption (VO2) and oxygen uptake (O2ext) at 0, 2, 4, 8, 24, 48 and 72 hours after injury.</p><p><b>RESULTS</b>The levels of MAP and IMBF markedly reduced, and LAC obviously increased in both groups after burn. MAP returned to 0 h level at 72 h post burn, while IMBF, and LAC were still higher or lower than 0 h levels. The level of MAP of GI + CAR group was significantly higher than that of GI group at 2 h, and those showed no significant differences between two groups after then. Carbochol administration led to a markedly higher levels of IMBF, and significant lower levels of LAC from 8 h after burn compared with those of GI group (P < 0.05 or P < 0.01). The levels of DO2 VO2 and Oext were reduced markedly after burn in both groups. At 72 h after burn, DOQ returned to 0 h level; while VO2 and Oext though still much lower than 0 h levels. The level of DO2. VO2 and Oext of GI + CAR group were significantly higher than those of GI group from 8 h after burn (P < 0.05 or P < 0.01). Three of six animals died in GI+ CAR group, which was lower than two of six in GI group.</p><p><b>CONCLUSION</b>The results indicates that carbachol promotes intragastric fluid resuscitative effect of burn shock by increasing oxygen delivery and decreasing hyperlactacidemia.</p>

The effects of oral rehydration on ischemia injury in gut in 40% blood volume loss in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of oral rehydration with glucose electrolyte solution(GES) on intestinal ischemia injury in 40% blood volume loss in rats.</p><p><b>METHODS</b>SD rats were randomly divided into three groups (n=24): oral rehydration without hemorrhage (GES), hemorrhage without oral rehydration (HS), hemorrhage resuscitated with oral GES(HS + GES). About 4% of total blood volume was bled from the right common carotid artery of rats to produce a model of hemorrhagic shock. GES, which volume was three times of blood loss was given to GES group and HS + GES group in 0.5 h, 1 h and 6 h by a gastric tube post bleeding. The intestinal blood flow(IBF) were measured by laser Doppler at 2 h, 4 h and 24 h post hemorrhage. Animals were sacrificed, and specimens of intestinal tissue was taken for evaluation of Na+ -K+ -ATPase, diamine oxidase (DAO) and the rate of tissue water content, and assessment of the intestinal pathological changes.</p><p><b>RESULTS</b>The IBF and the activity of Na+ -K+ -ATPase in HS+ GES group were dramatically higher than those in HS group (P < 0.05), and lower than those in GES group (P < 0.05). The water content of intestinal tissue in HS group were dramatically higher than those in GES group (P < 0.05), and lower than those at 2 h and 4 h, but dramatically higher than those at 24 h in HS + GES group. The activity of DAO at 24 h in HS+ GES group was higher than those in HS group (P < 0.05), and lower than those in GES group (P < 0.05). Less edema and hyperemia were found in HS + GES group than those in HS group at 24 h after bleeding.</p><p><b>CONCLUSION</b>It is indicated that oral rehydration alleviate edema and ischemia injury in gut by increasing intestinal blood flow and the activity of Na+ -K+ -ATPase and DAO in the resuscitation of hemorrhagic shock.</p>

Effects of oral rehydration On hemodynamics and microcirculatory perfusion in dogs with fatal hemorrhagic shock / 中华麻醉学杂志

Objective To investigate the effect of oral rehydration on hemedynamies and mierocirculatory perfusion in dogs with fatal hemorrhagic shock.Methods Twenty male Beagle dogs 16-20 months old weighing 8-12 ks were subjected to a loss of 40% of the total blood volume,then divided into 3 groups:no rehydration group (group NR,n=8),oral rehydration group(group OR,n=6)and intravenous rehydration group(group IR,n=6).Group NR received no treatment within 24 h after blood-letting.Group IR and OR were given glucose-electrolyte solution (GES) either by gastric tube or by intravenous infusion 3 times volume of the blood loss immediately after the establishment of the model.Then the lactated Ringer's solution,glucose saline and compound amino acid(2 times volume of the blood loss)were started to be given to supplement the physiological consumption from 24 h after blood-letting in each group.The MAP,cardiac index(CI),systemic vascular resistance (SVR),dp/dtmax,and intestinal mucoflal blood flow (IMBF) were determined before blood-letting(T0,baseline) and 2 h (T1),4 h(T2),8 h(T3),24 h(T4),48 h(T5) and 72 h(T6)after blood-letting.The fatality rate within 72 h after blood-letting and urinary output were calculated.Results The fatality rates were 63%,33%and O in group NR, OR and IR respectively, which showed significant difference between the groups (P < 0.05).Compared with the baseline values at To, MAP, CI and dp/dtmax were significantly decreased at T1-6, in group NR,at T1-5 in group OR and at T1-4 in group IR, and SVR was significantly increased, while IMBF decreased at each time point after blood-letting in the three groups ( P <0.05), but no significant change was found in MAP, CI and dp/dtmax at T6 in group IR and OR (P>0.05). MAP, CI, dp/dtmax , IMBF and urinary output were significantly higher, while SVR was significantly lower in group OR and IR than in group NR ( P < 0.05). MAP, CI,dp/dtmax, IMBF and urinary output were signiflcandy lower, while SVR was significantly higher in group OR than in group IR ( P < 0. 05). Conclusion Oral administration of GES 3 times volume of the blood loss within 24 h after fatal hemorrhagic shock can obviously improve the hemodynamics and microcirculatory perfusion, then improve the survival state and have obvious resuscitation efficacy.

Effects of oral rehydration on tissue perfusion, organ function and survival rate in rats with 40% blood volume loss hemorrhagic shock / 中华创伤杂志

Objective To investigate the effects of oral glucose-electrolyte solution (GES) on resuscitation of hemorrhagic shock induced by 40% blood volume loss in rats. Methods SD rats were randomly divided into three groups; oral GES without hemorrhagic shock (GES group, n = 16) , hemorrhage shock without fluid resuscitation (HS group, n = 20) and hemorrhagic shock resuscitated with oral GES (HS + GES group, n = 20). About 40% of total blood volume was bled from carotid artery of rats to produce a model of hemorrhagic shock. GES with a volume of three times of blood loss was given three times intragastrically at 0.5, 1 and 6 hours after hemorrhage. Mean arterial pressure (MAP) was measured constantly. Blood flow in liver, kidney, stomach and small intestines, and parameters like hemato-crit, plasma osmotic pressure, alanine aminotransferase (ALT) , creatinine (Cr) and diamine oxidase (DAO) were determined 24 hours after hemorrhage. Survival rates of the rats in three groups were calculated 24 hours after hemorrhage. Results MAPs of HS + GES group were 9. 7% and 10. 9% higher than those of HS group 4 and 24 hours after hemorrhage (P < 0. 05). The blood flow of liver, stomach and small intestines in HS + GES group were 18.6% , 88.4% and 22.0% respectively, higher than those in HS group(P <0.05 or P <0.01) 24 hours after hemorrhage. The hematocrit level of HS + GES group was significantly lower than that of HS group, while the levels of ALT, Cr and DAO in HS + GES group were significantly lower than those in HS group (P <0.01). The survival rate of rats in HS + GES group was 80% , which was significantly higher than 30% in HS group (P <0.01). Conclusions Oral rehydration can significantly improve MAP and tissue perfusion, maintain blood volume and plasma osmotic pressure, alleviate organ damage and hence promote the survival rates of rats with hemorrhagic shock.