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Objective To investigate the effect of human hepatocyte growth factor (hHGF) genetic modification on the ameliorating effects of mesenchymal stem cells (MSCs) implantation on pulmonary microvascular rarefaction in a rat model of pulmonary hypertension (PH).Methods MSCs were obtained from F344 rats and transduced with lentiviral vector modified with human HGF (hHGF-MSCs) or empty vector (EGFP-MSCs).Sixty-six 7 week old male F344 rats weighing 180-250 g were used in this study.PH was induced by left pneumonectomy and subcutaneous monocrotaline (MCT) 60 mg/kg injected at 2 weeks after operation.The animals with PH were randomly divided into 3 groups:control group (group C),EGFP-MSCs group (group E) and HGF-MSCs group (group H).Groups H and E received hHGF-MSCs or EGFP-MSCs 5 × 105 in DMEM 1 ml iv at 3 weeks after subcutaneous MCT injection,while group C received plain DMEM 1 ml.Mean pulmonary arterial pressure (mPAP) was measured and right ventricular hypertrophy and angiogenesis in the lung were assessed and the content of rat HGF (rHGF) and hHGF protein in lung tissue and pulmonary capillary density (by immuno-histochemistry) was measured at 2 weeks after MSCs implantation.The survival rates within 45 days after MCT administration were compared among the 3 groups.Results No hHGF was detected in groups C and E.Both hHGF-MSCs and EGFP-MSCs significantly reduced MPAP and right ventricular hypertrophy and increased pulmonary capillary density and survival rates in groups H and E as compared with group C and the efficacy of hHGF-MSCs was significantly greater than that of EGFP-MSCs.Barium angiography revealed that distal pulmonary vasculature was significantly increased in group H as compared with groups E and C.The survival of the rats receiving hHGF-MSCs was significantly longer in group H than that in groups E and C.Conclusion hHGF genetic modification can improve the ameliorating effects of MSCs implantation on PH-related microvascular rarefaction.
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Objective To investgate the changes in the expression of hepatocyte growth factor (HGF)and c-met in the lungs in a rat model of pulmonary hypertension.Methods Eighty 7 week old male SD rats weighing 180-250 g were randomly divided into 2 groups ( n =40 each ):control group (group C) and pulmonary hypertension group (group PH).Pulmonary hypertension was induced by left pneumonectomy and subcutaneous monocrotaline (MCT) 60 mg/kg 2 weeks later.Pulmonary artery pressure and the ratio between the weight of right ventricle and left ventricle + interventricular septum ( RV/LV + S) were measured at 7,14,21 and 28 d after MCT administration.HGF and c-met protein and mRNA expression and TGF-β content in the lung tissue were determined.Results Pulmonary hypertension and right ventricular hypertrophy associated with hypertrophy of pulmonary artery tunica media and muscularization of small pulmonary arteries developed after MCT administration in PH group.In PH group HGF protein and mRNA expression in the lungs was significantly down-regulated as compared with group C.There were no significant differences in c-met protein and mRNA expression in the lungs between the 2 groups.The TGF-β content in the lungs was significantly increased in group PH as compared with group C.Conclusion Decrease in HGF production in the lungs plays an important role in the pulmonary hypertension.Increasing of pulmonary TGF-β may play an important role in the down-regulation of pulmonary HGF expression during pulmonary hypertension.
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ObjectiveTo investigate the effect of ketamine on nicotine-induced current in rat superior cervical ganglion neurons.MethodsNewborn Wistar rats were used in this study.Neurons were isolated enzymatically from superior cervical ganglia of newborn rats in an aseptic condition and cultured in 90％ DMEM/F12,10％ horse serum containing penicillin 100 μg/ml for 5-7 d.Nicotine-induced current was measured and recorded using whole-cell patch clamp technique.A mixture of nicotine 50 μmol/L and different concentrations of ketamine ( 10,25,50,100 μmol/L) was added to the isolated neurons.The effect of ketamine on nicotine-induced current was evaluated.ResultsNicotine-induced peak current was inhibited by ketamine in a concentration-dependent manner.The time constant of fast and slow desensitizing phase of the nicotine acetylcholine receptor was shortened after being exposed to the mixture of nicotine 50 μmol/L + 50 or 100 μmol/L ketamine as compared to nicotine 50 μmol/L-induced current.The median effective concentration of ketamine inhibiting nicotine-induced current was less than 20 μmol/L.ConclusionKetamine can decrease nicotine-induced current in rat superior cervical ganglion neurons in a concentration-dependent manner indicating that inhibition of sympathetic activity is involved in the mechanism of decrease in BP by ketamine in specific condition.
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To investigate the protective effect of genistein on endotoxin-induced acute lung injury in rats, and explore the underlying mechanisms, 32 male Sprague-Dawley rats were randomly divided into 4 experimental groups: saline control, genistein alone, lipopolysaccaride alone, and genistein pretreatment. Each treatment group consisted of eight animals. Animals were observed for 6 h after LPS challenge, and the wet/dry (W/D) weight ratio of the lung and bronchoalveolar lavage fluid(BALF) protein content were used as a measure of lung injury. Neutrophil recruitment and activation were evaluated by BALF cellularity and myeloperoxidase (MPO) activity. RT-PCR analysis was performed in lung tissue to assess gene expression of ICAM-1. The histopathological changes were also observed using the HE staining of lung tissue. Our results showed that lung injury parameters, including the wet/dry weight ratio and protein content in BALF, were significantly higher in the LPS alone group than in the saline control group (P＜0.01). In the LPS alone group, a larger number of neutrophils and greater MPO activity in cell-free BAL and lung homogenates were observed when compared with the saline control group (P＜0.01). There was a significant increase in lung ICAM-1 mRNA in response to LPS challenge (P＜ 0. 01, group L versus group S).Genistein pretreatment significantly attenuated LPS-induced changes in these indices. LPS caused extensive lung damage, which was also lessened after genistein pretreatment. All above-mentioned parameters in the genistein alone group were not significantly different from those of the saline control group. It is concluded that genistein pretreatment attenuated LPS-induced lung injury in rats.This beneficial effect of genistein may involves, in part, an inhibition of neutrophilic recruitment and activity, possibly through an inhibition of lung ICAM-1 expression.
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BACKGROUND: As an important part of systemalimbica, hippocampus involves in emotion, perceiving and learning memory and can be affected by anesthesia.OBJECTIVE: With target controlled infusion of propofol, the depth of anesthesia was well controlled. And under anesthesia in various depths, cfos gene expressions in different regions of hippocampus in rabbits were detected to find the target site for central nervous inhibition by propofol.DESIGN :It was a randomized controlled study.SETTING:Department of Anesthesiology ,Shenzhen Second People's Hospital; Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: The experiment was conducted in the Neurobiological Laboratory of Tongji Medical College, Huazhong University of Science and Technology from May 2000 to June 2001. Thirty Japanese white rabbits were selected and randomly divided into control group, light anesthesia group and deep anesthesia group, with 10 rabbits in each group.METHODS:Intravenous cannulas were placed in external jugular vein (EJV) and femoral artery in all animals. According to the propofol plasma concentration, the infusion of propofol and the depths of anesthesia were well controlled. In light anesthesia group, the plasma concentration of propofol was (9.28±0.12)mg/L. In deep anesthesia group, the plasma concentration of propofol was (11.63±0.29)mg/L. Thirty minutes after being anesthetized, the animals in the two experimental groups were decapitated and the animals in control group were killed by air embolism through ear vein. Coronal sections were sliced continuously, in thickness of 7μm and 1 slice in 100 μm tissue was selected. In situ hybridization was performed to detect the c-f os mRNA in Area CA1, CA3 and dentate gyrus of the hippocampus. In each rabbit, 5 sections were selected randomly.Under a light microscope, photos were taken in 15-20 fields. And then average absorbency and average grayscale were calculated. The grayscale scores were classified as 256 scales. A lower grayscale score indicated a higher positive rate.MAIN OUTCOME MEASURES: ①Under various depths of anesthesia,in situ hybridization results of Area CA1, CA2 and dentate gyrus of the anesthesia, average grayscale scores of Area CA1, CA2 and dentate gyrus of the hippocampus in rabbits were assessed.② Under various depths of anesthesia, average grayscale scores of Area CA1, CA2 and dentate gyrus of the hippocampus in rabbits were calculated.RESULTS:Thirty rabbits entered the statistical analysis procedure.①Under various depths of anesthesia, in situ hybridization results of Area CA1 of the hippocampus in rabbits: In control group, brown, sparse or dense, light-stained or deep-stained c-fos positive cells could be observed. In light anesthesia group, dense, moderately stained c-fospositive neurons could be observed. In deep anesthesia group, cells were denser with deeper stained cytoplasma. ② Under various depths of anesthesia, in situ hybridization results of dentate gyrus of the hippocampus in rabbits: In light anesthesia group, positive cells were strongly stained in deep brown with transparent and vacuolar nuclei. In deep anesthesia group, a large number of c-fos positive cells in great dense could be observed. ③Under various depths of anesthesia, grayscale scores of different regions of the hippocampus in rabbits: Compared with control group, grayscale scores of Area CA1 and dentate gyrus of the hippocampus were significantly decreased in both light and deep anesthesia groups [(168±5), (80±7), (59±5)% ,P ＜ 0.05; (163±8),(103±15), (67±6)%,P ＜ 0.05,P ＜ 0.01]. This was more significant in deep anesthesia group than in light anesthesia group (P ＜ 0.01 ). For Area CA3, the grayscale scores in each group were similar.CONCLUSION: ①With the increasing depth of propofol anesthesia, c-fos gene expression is increased in hippocampus in rabbits. ② After anesthesia, the average grayscale score of Area CA1 and dentate gyrus of the hippocampus are significantly decreased, and this is more significant after deep anesthesia. However, there is no significant change in Area CA3. This indicates that the central inhibitory receptor sites of propofol are various in different brain regions, which supposes that the Area CA3 is not the central receptor sites of propofol.
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The aim of this study was to determine the role of neutrophil collagenase in the pathogenesis of acute lung injury induced by endotoxin. 28 Sprague-Dawley were randomized into control group and LPS-enduced groups. Samples of left lung were obtained in 2 h (group L1), 6 h (group L2), 12 h (group L3) after intravenous LPS. Immunohistochemsitry was employed for detection of expression of neutrophil collagenase. Pathological scores, lung wet/dry weight ratio and the number of neutrophils were measured. The results showed that the concentration of neutrophil collagenase in LPS-enduced groups (group L1, L2, L3) were significantly higher than that of control group (P<0.01). Pathological scores, lung wet/dry weight ratio and the number of neutrophils in LPS-enduced groups (group L1, L2, L3) were also significantly higher than that of control group (P<0.01). Moreover, among group L1, L2 and L3, there were significant correlations in concentration of neutrophil collagenase and pathological scores, lung wet/dry weight ratio, the number of neutrophils (P<0.05). The present study showed that neutrophil collagenase play an important role in the pathogenesis and progress of endotoxic acute lung injury.
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Endotoxins , Lung/pathology , Matrix Metalloproteinase 8/metabolism , Random Allocation , Rats, Sprague-Dawley , Respiratory Distress SyndromeABSTRACT
The aim of this study was to determine the role of neutrophil collagenase in the pathogenesis of acute lung injury induced by endotoxin. 28 Sprague-Dawley were randomized into control group and LPS-enduced groups. Samples of left lung were obtained in 2 h (group L1), 6 h (group L2), 12 h (group L3) after intravenous LPS. Immunohistochemsitry was employed for detection of expression of neutrophil collagenase. Pathological scores, lung wet/dry weight ratio and the number of neutrophils were measured. The results showed that the concentration of neutrophil collagenase in LPS-enduced groups (group L1, L2, L3) were significantly higher than that of control group (P<0.01). Pathological scores, lung wet/dry weight ratio and the number of neutrophils in LPS-enduced groups (group L1, L2, L3) were also significantly higher than that of control group (P<0.01). Moreover, among group L1, L2 and L3, there were significant correlations in concentration of neutrophil collagenase and pathological scores, lung wet/dry weight ratio, the number of neutrophils (P<0.05). The present study showed that neutrophil collagenase play an important role in the pathogenesis and progress of endotoxic acute lung injury.
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Animals , Female , Male , Rats , Endotoxins , Lung , Pathology , Matrix Metalloproteinase 8 , Metabolism , Random Allocation , Rats, Sprague-Dawley , Respiratory Distress Syndrome , PathologyABSTRACT
To assess the potential therapeutic effect of propofol in the treatment of endotoxemia, 76 rats were randomly assigned to 5 groups: control group(A), endotoxemic group(B), pre-treatment group(C), simultaneous treatment group(D) and post-treatment group(E). Five h after endotoxin injection, PO2, pH, MAP, plasma concentrations of Nitrite/nitrate (NO2-/NO3-) and mortality rates were assessed in each group. After the rats were sacrificed, lung tissue was sampled to measure myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-alpha contents. It was found that endotoxin injection produced progressive hypotension, metabolic acidosis, and a large increase in the plasma NO2-/NO3- concentrations and increased mortality rates in 5 h. Endotoxin injection significantly increased MPO activity and TNF-alpha contents in lung tissue (P < 0.01 or P < 0.05). These changes response to endotoxin were significantly attenuated in the groups B, C and D. But these beneficial effects were blunted in the group E. The results suggest that propofol administration may offer advantages in endotoxemia.
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Animals , Male , Rats , Free Radical Scavengers , Therapeutic Uses , Lipopolysaccharides , Lung , Metabolism , Nitric Oxide , Blood , Peroxidase , Metabolism , Propofol , Therapeutic Uses , Random Allocation , Rats, Wistar , Shock, Septic , Drug Therapy , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
To investigate the effects of treatment with propofol administration at different time point in acute lung injury of endotoxin-induced shock in rats. 76 male wistar rats were randomly assigned to five groups: A] control group; B] endotoxemic group, receiving intravenous lipopolysaccharide [LPS] 8mgkg -1; C] pretreatment group, treated identically to endotoxemic group with the additional administration of propofol [5mgkg -1 bolus, followed by infusion at 10 mgkg -1h -1] of lhr prior to the injection of LPS; D] simultaneously treatment group, treated identically to endotoxemic group with the additional administration of propofol simultaneously with the injection of LPS; E] post-treatment group, which was treated identically to endotoxemic group except for administration of propofol lhr after the injection of LPS. PaO 2, pH, MAP and survival rate were recorded and plasma NO, TNF-alpha were measured during 5-hr after the injection of LPS. After the rats were killed, lung tissue was sampled to measured expression of inducible nitric oxide synthase [iNOS], nitrotyrosine [NT], myeloperoxidase [MPO] activity, malondialdehyde [MDA], wet-to-dry lung weight ratio [W/D], and pulmonary permeability index [PPI]. Compared with the endotoxemic group, both the pretreatment and simultaneously treatment groups, significantly improved PaO 2, pH, MAP and 5th hour survival rate of rats, and attenuated endotoxin-induced increased iNOSmRNA, NT expression, MPO activity and MDA level in lung tissue, and decreased pulmonary microvascular permeability, TNF alpha, NO in plasma. But these beneficial efficacies were blunted in the post-treatment group. These findings showed that propofol administration may provide protective effects on acute lung injury in endotoxin-induced shock
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Animals, Laboratory , Respiratory Distress Syndrome/drug therapy , Endotoxins , Rats, Wistar , Nitric Oxide , Tumor Necrosis Factors , Peroxidase , Lipopolysaccharides , EndotoxemiaABSTRACT
AIM: To investigate the effects of rosiglitazone(ROSI),an agonist of peroxisome proliferator-activated receptor ?(PPAR?),on the lung expression of intercellular adhesion molecule-1(ICAM-1) and cytokine-induced neutrophil chemoattractant(CINC) in rats with acute lung injury. METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control group,ROSI group,GW9662(a PPAR? antagonist) group,lipopolysaccharide(LPS,6 mg/kg,iv) group,ROSI-LPS group(0.3 mg/kg ROSI iv 30 min prior to LPS) and GW9662-ROSI-LPS group(0.3 mg/kg GW9662,iv,20 min before ROSI).Four hours after LPS injection,wet/dry weight(W/D) ratio,myeloperoxidase (MPO) activity,malondialdehyde(MDA) and CINC-1 concentrations were assayed in the lung tissues.Immunohistochemical analysis of ICAM-1 expression was also studied.RESULTS: Pretreatment with ROSI significantly attenuated LPS-induced increases in W/D ratio,MPO activity,MDA and CINC-1 concentrations as well as ICAM-1 expression in the lung tissues.The specific PPAR? antagonist GW9662 antagonized the effects of ROSI.CONCLUSION: Pretreatment with ROSI reduces LPS-induced lung injury in rats.The mechanism involves inhibition of the lung expression of ICAM-1 and CINC-1 by the activation of PPAR?.
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Objective To investigate the effects of genistein pretreatment on endotoxin-induced acute lung injury in rats and assess the possible mechanism. Methods Thirty-two male Wistar rats weighing 240-280 g were randomly divided into 4 groups ( n = 8, each group) : group Ⅰ control; group Ⅱ genistein; group ? LPS and group Ⅳ genistein pretreatment. The jugular vein was cannulated for administration of fluid and drug. The animals were anesthetized with intraperitoneal 3% pentobarbital 40 mg? kg-1 . In group Ⅰ and Ⅱ Ⅳ normal saline (NS) 1 ml?kg-1 was Ⅳ given 30min after IP NS 1 ml?kg-1 (Ⅰ ) or genistein 50 mg?kg-1 (Ⅱ ). In group ? and Ⅳ LPS 6 ml? kg-1 was Ⅳ given 30 min after IP NS 1 ml?kg-1 (?) or genistein 50 mg? kg -1 (Ⅳ). Four hours after.LPS injection, rats were sacrificed. The lungs were removed for evaluation of histological injury and determination of wet/dry lung weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, expression of TNF-f55 mRNA, HO-1 mRNA, TNF-f55, and HO-1. Bronchoalveolar lavage fluid (BALF) was collected for determination of PMN count, protein content, and MPO activity.Results LPS administration induced marked lung injury and significant increases in W/D ratio, MPO activity, and MDA content in the lung tissues, and PMN count, protein content, and MPO activity in BALF. All of these changes were significantly reduced by genistein pretreatment. Genistein also markedly suppressed LPS-induced expression of TNF-a mRNA and protein, and enhanced LPS-induced expression of HO-1 mRNA and protein. Conclusion Pretreatment with genistein has protective effect against endotoxin-induced acute lung injury. The underlying mechanism is via an inhibition of neutrophilic recruitment and activity, a down-regulation in TNF-f55 production, and a up-regulation in HO-1 expression.
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To investigate the effects of cardiopulmonary bypass (CPB)on the aquired platelet damage and the relationship between the aquired platelet damage and non-surgical postoperative bleeding. Method: Platelet counts (BPC), alphagranule membrane protein (GMP-140), ?-thromboglobulin (?-TG), platelet factor 4 (PF_4), and 5-hydrooxytryptamine levels were measured in 20 patients undergoing cardiac surgery before CPB, 30 min during CPB, 10 min after CPB, and 2, 12, and 24 hours postoperatively. The numbers of patients with bleeding volume over 200 ml within 24 hours postoperatively were counted. Result: BPC decreased markedly during CPB, but never decreased to the degree of 50?10~9/L. GMP-140, ?-TG, PF_4 and 5-HT levels were significantly increased during CPB until 12 hours postoperatively. Eight patients(40%) got the bleeding volume over 200 ml within 24 hours postoperatively. Conclusion: Platelet release reaction is violent during cardiac surgery with CPB. A large number of platelets dysfunctioned because of granula releasing or damage may be the main cause of non-surgical postoperative bleeding.
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To investigate the effects of clonidine on controlled hypotension induced by sodium nitroprusside,twenty-four patients (male 17,femai 7,aged 20 to 58 years,ASA Ⅰ to Ⅱ)scheduled for elective craniotomy,were randomly assigned to two groups:control group (Ⅰ,n=12),clonidine group (Ⅱ,n=12) with premedication of clonidine 5?g/kg P. O.. The MAP of both groups decreased by 40% with the infusion of 0.01% sodium nitroprusside solution (SNP). The results showed that the blood pressure was more easily reduced and maitained in group Ⅱ,and the MAP after discontinuing of SNP in group Ⅱ was lower than in group Ⅰ(P
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0.05 ) ; propofol 500 /?mol?L-1 had dual effects : in 2/3 cells EPSCs were reduced to 67.5 % of the basiline values ( P
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Objective To detect the genes differentially expressed in sepsis-injured lungs and discover new genetic targets for management of sepsis-induced acute lung injury (ALI) and evaluate the role of cDNA microarray in the study of molecular pathogenesis of sepsis. Methods In a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), the gene expression patterns of the lungs of the animals in sepsis group and control group (Sham-operation ) were screened at 6 h and 12 h after CLP by using a commercially available cDNA microarray chips containing 2 201 cDNA clones. The cDNA of differentially expressed unique genes were sorted and analyzed. Results Of the 2 201 cDNA clones on the chip, 80 known unique genes had significant differential expression at 6 and/or 12 h after CLP as compared with those of mice in control group. 40 of the 80 genes were up-regulated and 40 down-regulated and they were related with a range of genetic functions, such as cell defence or immune/inflammatory reaction, acute-phase reaction or heat-shock reaction, redox regulation, cytoskeleton, cell apoptosis, cell signaling and cell metabolism etc. By functional analysis of these differentially expressed genes, some unique genes or expression patterns were interpreted in the context of septic ALI process and warrant further investigation. Conclusion cDNA microarray technique provides a powerful new tool for detecting differentially expressed genes and analyzing gene expression patterns in sepsis-injured tissues. Further study using this technique may yield great insight into the molecular pathologic mechanism of sepsis and discern new targets for therapeutic interventions.
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Objective To investigate the effects of propofol administered at different intervals on acute lung injury induced by endotoxin shock and the mechanism in rats.Methods Seventy-six healthy adult male Wistar rats, weighing 250-290 g were anesthetized with 30 % pentobarbital sodium 30 mg. kg-1 ip. Carotid artery and jugular vein were cannulated for BP monitoring and administration of drugs and fluid. The animals were randomly divided into 5 groups : group A received only normal saline (NS) ( n = 8) ; group B received LPS 8 mg' kg and NS iv ( n =17); group C-E received a bolus of propofol 5 mg .kg-1 iv, 1 h before (group C) or together with (group D) or 1 h after intravenous LPS (group E) followed by propofol infusion at 10 mg . kg-1 . h-1 ( n = 17 in each group). The animals were observed for 5 h after LPS. Blood samples were taken from femoral artery before (baseline) and 1, 3 , 5 h after LPS for determination of PaO2 ,pH, and serum TNF-a and NO levels. The survival rates of the animals in the 5 groups during the 5 h after LPS were compared. The animals were sacrificed and the lungs were removed at the end of 5 hour observation for determination of lung TNF-a and MDA content and myeloperoxidase (MPO) activity and microscopic examination. Results Propofol given 1h before (group C) and simultaneously with LPS (group D) significantly attenuated the decrease in MAP, pH and PaO2 and increase in serum contents of TNF-a and NO and lung TNF-a, MDA contents and MPO activity induced by LPS. The 5 hour survival rate was also significantly higher in group C and D than that in group B. Conclusion Early propofol administration is beneficial during endotoxin-induced shock.
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To investigate the effect of premedication with clonidine on the concentrations of plasma catecholamine (CA), renin, angiotension Ⅱ (A Ⅱ ) and carbohydrate metabolism during eardiopulmonary bypass (CPB). Method: Twenty patients scheduled for cardiac surgery were randomly divided into two groups: clonidine group and control group. Oral premedication with clonidine 5?g?kg~(-1) was taken in colndine group 60 rain before anesthesia in duction in addition to common same premedication in both groups. Arterial plasma concentrations of CA,renin, AⅡ, blood suger, pyruvic acid, lactic acid were measured before anesthesia, before CPB, 30,60,90 and 120 min following CPB and 30 rain after CPB. Result: The levels of CA, blood suger, pyruvic acid and lactic acid increased significantly during CPB in both groups, but were higher markedly in control group than those in clonidine group (P
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Objective: To evaluate the safety of controlled hypotension produced by human ?-calcitonin gene-related peptide(?-hCGRP)and sodium nitroprusside. Method: Twenty SD rats were randomly divided into ?-hCGRP(C) and sodium nitroprusside(S) groups. Animals in group C were infused intravenously with 0.001％ ?-hCGRP and those in group S with 0.01％ sodium nitroprusside. The mean blood pressure of rat was reduced to 6.7kPa and maintained for 30 min. Cerebral glucose,lactate,ATP, and phosphocreatine levels were measured at 0 and 30th min of hypotension. Result: Cerebral glucose level increased slightly,lactate level decreased significantly,ATP and phosphocreatine contents did not change in group C at 30th min of hypotension compared with those at 0 min of hypotension,respectively.Cerebral glucose level increased slightly,lactate concentration increased significantly,ATP and phosphocreatine contents decreased significantly in group S at 30th min of hypotension in comparison with those at 0 min of hypotension, respectively. Conclusion: Hypotension induced with alpha-hCGRP can maintain adequate cerebral oxygen supply,but with sodium nitroprusside may cause cerebral hypoxia.
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Objective:The somatosensory evoked cerebral potential (SEP)was used to assess the analgesia effect of clonidine. Method: Twenty-three SD rats was randomly divided into two groups, the control group (n=8) and clonidine group (n=15). The control group rats was injected 1 ml normal saline to peritoneal cavity and the clonidine group rats was injected 10mg(1ml) clonidine peritoneally. The SEP waves were recorded in both groups at preinjection and 20,40,60 min after injection. Pain relief ratio was calculated according to the N15-P25 peak-peak amplitude of SEP wave. Result:SEP amplitude and latency were markedly reduced in clonidine group and remained unchanged in control group. The peak Pain relief ratio was 80. 6％at 20-40 min after clonidine administration. Conclusion:Clonidine does have a effect of pain relief
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Objective To investigate the effects of rosiglitazone (ROSI), a potent agonist of peroxisome proliferator- activated receptor ?( PPAR?) on acute lung injury induced by endotoxin. Methods Thirty-six male Wistar rats weighing 200-250 g were randomly divided into 6 groups (n = 6 per group): group I control; group II ROSI; group III GW; group IV LPS; group V ROSI + LPS and group VI GW + ROSI + LPS. The animals were anesthetized with intraperitoneal 3 % pentobarbital 50 mg ? kg -1 . The jugular vein was cannulated for administration of fluid and drug. In group I , II and III normal saline (NS) 2 ml was given 30 min after IV 10% DMSO 2 ml? kg-1( I ), ROSI 0.3 mg?kg-1(dissolved in DMSO) or GW9662 (PPAR? antagonist) 0.3 mg?kg-1 ( III ) . In group IV , V and VI instead of NS LPS 6 mg? kg-1 was given 30 min after 10% DMSO ( IV ) or ROSI( V , VI). In group VI GW9662 0.3 mg?kg-1 was given IV 20 min before ROSI. The rats were sacrificed and the lungs were removed for microscopic examination and determination of wet/dry lung weight ( W/D) ratio and lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) and NO content. The lung was also assessed for expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine ( NT) using Western blot analysis or immuno-histochemistry.Results LPS induced marked lung injury and significant increase in W/D ratio, MPO activity, MDA and NO content in the lung. All of these changes were significantly attenuated by pretreatment with ROSI. Pretreatment also significantly suppressed LPS-induced expression of iNOS protein and formation of nitrotyrosine in the lung. The specific PPAR? antagonist GW9662 counteracted the effects of ROSI. Conclusion Pretreatment with has protective effect against endotoxin-induced ALL The underlying mechanism is via the activation of PPAR?.