Prevention against and treatment of doxorubicin-induced acute cardiotoxicity by dexrazoxane and schisandrin B / 药学学报

In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.

The plateau zokors' learning and memory ability is related to the high expression levels of foxP2 in the brain / 生理学报

Plateau zokor (Myospalax baileyi) is a subterranean mammal. Plateau zokor has high learning and memory ability, and can determine the location of blocking obstacles in their tunnels. Forkhead box p2 (FOXP2) is a transcription factor implicated in the neural control of orofacial coordination and sensory-motor integration, particularly with respect to learning, memory and vocalization. To explore the association of foxP2 with the high learning and memory ability of plateau zokor, the cDNA of foxP2 of plateau zokor was sequenced; by using plateau pika as control, the expression levels of foxP2 mRNA and FOXP2 protein in brain of plateau zokor were determined by real-time PCR and Western blot, respectively; and the location of FOXP2 protein in the brain of plateau zokor was determined by immunohistochemistry. The result showed that the cDNA sequence of plateau zokor foxP2 was similar to that of other mammals and the amino acid sequences showed a relatively high degree of conservation, with the exception of two particular amino acid substitutions [a Gln (Q)-to-His (H) change at position 231 and a Ser (S)-to-Ile (I) change at position 235]. Higher expression levels of foxP2 mRNA (3-fold higher) and FOXP2 protein (>2-fold higher) were detected in plateau zokor brain relative to plateau pika brain. In plateau zokor brain, FOXP2 protein was highly expressed in the cerebral cortex, thalamus and the striatum (a basal ganglia brain region). The results suggest that the high learning and memory ability of plateau zokor is related to the high expression levels of foxP2 in the brain.

Differences of glycolysis in skeletal muscle and lactate metabolism in liver between plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) / 生理学报

The plateau pika (Ochotona curzoniae) and plateau zokor (Myospalax baileyi) are specialized native species of the Qinghai-Tibetan plateau. The goal of this study was to examine physiological differences in skeletal muscle glycolysis and hepatic lactate metabolism between these two species. The partial sequence of pyruvate carboxylase (PC) gene was cloned and sequenced. The mRNA expression levels of PC and lactate dehydrogenases (LDH-A, LDH-B) were determined by real-time PCR. The enzymatic activity of PC was measured using malic acid coupling method. The concentration of lactic acid (LD) and the specific activities of LDH in liver and skeletal muscle of two species were measured. The different isoenzymes of LDH were determined by native polyacrylamide gel electrophoresis (PAGE). The results showed that, (1) LDH-B mRNA level in skeletal muscle of plateau zokor was significantly higher than that of plateau pika (P < 0.01), but no differences was found at LDH-A mRNA levels between them (P > 0.05); (2) PC, LDH-A and LDH-B mRNA levels in liver of plateau pika were significantly higher than those of plateau zokor (P < 0.01); (3) The LDH activity and concentration of LD in skeletal muscle and liver, as well as the PC activity in liver of plateau pika were significantly higher than those of plateau zokor (P < 0.01); (4) The isoenzymatic spectrum of lactate dehydrogenase showed that the main LDH isoenzymes were LDH-A4, LDH-A3B and LDH-A2B2 in skeletal muscle of plateau pika, while the main LDH isoenzymes were LDH-AB3 and LDH-B4 in skeletal muscle of plateau zokor; the main isoenzymes were LDH-A3B, LDH-A2B2, LDH-AB3 and LDH-B4 in liver of plateau pika, while LDH-A4 was the only isoenzyme in liver of plateau zokor. These results indicate that the plateau pika gets most of its energy for sprint running through enhancing anaerobic glycolysis, producing more lactate in their skeletal muscle, and converting lactate into glucose and glycogen in the liver by enhancing gluconeogenesis. As a result, the plateau pika has a reduced dependence on oxygen in its hypoxic environment. In contrast, plateau zokor derives most of its energy used for digging activity by enhancing aerobic oxidation in their skeletal muscle, although they inhabit hypoxic underground burrows.

Association between serum YKL-40 levels and endothelial function in hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between serum YKL-40 levels and endothelial function in patients with essential hypertension (EH).</p><p><b>METHOD</b>Sixty EH patients [34 male, aged between 43 - 76 years, mean (59 ± 7) years] and 30 healthy subjects [17 male, mean age (57 ± 5) years] were enrolled in this study. Serum YKL-40 levels were measured by enzyme immunoassay (ELISA). Endothelial function [endothelin-1 (ET-1), nitric oxide (NO), flow-mediated dilatation (FMD)] was also measured. EH patients were further divided to no metabolic syndrome and metabolic syndrome group.</p><p><b>RESULTS</b>Serum uric acid, ET-1, hs-CRP were significantly higher while serum NO, FMD and NMD were significantly lower in EH group than in control group (all P < 0.05). YKL-40 was significantly higher in EH group than in the control group [51.7 (35.6 - 341.9) µg/L vs. 33.2 (23.3 - 167.3) µg/L, P < 0.05] and significantly higher in EH patients with metabolic syndrome than in EH patients without metabolic syndrome (152.3 µg/L vs. 94.2 µg/L, P < 0.05). In this cohort, serum YKL-40 level was positively correlated with SBP, DBP, BMI, TG and hsCRP(r = 0.360, 0.303, 0.281, 0.216, 0.530, all P < 0.05)but not correlated with FMD, ET-1 and NO (all P > 0.05).</p><p><b>CONCLUSIONS</b>Serum YKL-40 levels are increased compared to normal controls and positively correlated with blood pressure level but not with endothelial function parameters in hypertensive patients. Serum YKL-40 level might thus be used as a biomarker reflecting inflammation status other than endothelium function in hypertensive patients.</p>

Functional difference of malate-aspartate shuttle system in liver between plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) / 生理学报

To explore the adaptive mechanisms of plateau zokor (Myospalax baileyi) to the enduring digging activity in the hypoxic environment and of plateau pika (Ochotona curzoniae) to the sprint running activity, the functional differences of malate-aspartate shuttle system (MA) in liver of plateau zokor and plateau pika were studied. The ratio of liver weight to body weight, the parameters of mitochondria in hepatocyte and the contents of lactic acid in serum were measured; the open reading frame of cytoplasmic malate dehydrogenase (MDH1), mitochondrial malate dehydrogenase (MDH2), and the partial sequence of aspartate glutamate carrier (AGC) and oxoglutarate malate carrier (OMC) genes were cloned and sequenced; MDH1, MDH2, AGC and OMC mRNA levels were determined by real-time PCR; the specific activities of MDH1 and MDH2 in liver of plateau zokor and plateau pika were measured using enzymatic methods. The results showed that, (1) the ratio of liver weight to body weight, the number and the specific surface of mitochondria in hepatocyte of plateau zokor were markedly higher than those of plateau pika (P < 0.01 or P < 0.05), but the content of lactic acid in serum of plateau pika was significantly higher than that of plateau zokor (P < 0.01); (2) MDH1 and MDH2 mRNA levels as well as their enzymatic activities in liver of plateau zokor were significantly higher than those of plateau pika (P < 0.01 or 0.05), AGC mRNA level of the zokor was significantly higher than that of the pika (P < 0.01), while no difference was found at OMC mRNA level between them (P > 0.05); (3) mRNA level and enzymatic activity of MDH1 was significantly lower than those of MDH2 in the pika liver (P < 0.01), MDH1 mRNA level of plateau zokor was markedly higher than that of MDH2 (P < 0.01), but the activities had no difference between MDH1 and MDH2 in liver of the zokor (P > 0.05). These results indicate that the plateau zokor obtains ATP in the enduring digging activity by enhancing the function of MA, while plateau pika gets glycogen for their sprint running activity by increasing the process of gluconeogenesis. As a result, plateau pika converts the lactic acid quickly produced in their skeletal muscle by anaerobic glycolysis and reduces dependence on the oxygen.

The expression of nicotinamide phosphoribosyl transferase and vascular endothelial growth factor-A in gastric carcinoma and their clinical significance / 中华外科杂志

<p><b>OBJECTIVES</b>To study the expression of nicotinamide phosphoribosyl transferase (Nampt) and vascular endothelial growth factor-A (VEGF-A) in gastric carcinoma and investigate their correlations to clinicopathologic features and prognostic significance.</p><p><b>METHODS</b>The proteins of Nampt and VEGF-A in 68 specimens of gastric carcinoma and 59 specimens normal gastric tissue were detected by immunohistochemistry during January 2000 to December 2004, and the 68 patients were followed up.</p><p><b>RESULTS</b>Nampt protein was detected in the cytoplasm of both tissues, and Nampt in gastric carcinoma (13 ± 5) were significantly higher than that in normal gastric tissue (6 ± 3) (t = 7.46, P < 0.01). The expression of Nampt was correlated to invasive depth (F = 4.693, P = 0.034), lymph node metastasis (F = 4.027, P = 0.049), clinical TNM stage (F = 9.979, P = 0.002), but not to gender, age, tumor location, tumor size, differentiation (P > 0.05). The expression of Nampt is correlated with survival of patients that underwent surgical resection for gastric cancer. The survival rate of patients in negative of Nampt was very higher than that of the positive patients, and its co-expression with VEGF-A showed a trend towards poorer survival. The positive correlation was found between the expression of Nampt and VEGF-A in gastric carcinoma (r = 0.293, P = 0.015).</p><p><b>CONCLUSIONS</b>The expression of Nampt is positively correlated to that of VEGF-A in gastric carcinoma. The correlation between the expression of Nampt and VEGF-A in gastric carcinoma plays an important role cooperatively in carcinogenesis, development and metastasis of gastric carcinoma.</p>

Gene coding and mRNA expression of vascular endothelial growth factor as well as microvessel density in brain of plateau zokor: comparison with other rodents / 生理学报

Vascular endothelial growth factor (VEGF) plays an important role in tissues angiogenesis. The adaptation of animals to hypoxic environment is relative to the microvessel density (MVD) in tissues. To further explore the adaptation mechanisms of plateau zokor (Myospalax baileyi) to the hypoxic-hypercapnic burrows, the VEGF mRNA and the MVD in cerebral tissues of the plateau zokor were studied. Total RNA was isolated from liver, and VEGF cDNA was obtained by RT-PCR, then the VEGF cDNA was cloned and sequenced. The coding sequence of plateau pika (Ochotona curzniae), rat (Rattus norvegicus) and mouse (Mus musculus) VEGF cDNA are obtained from GenBank, and the nucleotide and amino acid sequence homology of plateau zokor VEGF cDNA coding sequence with that of plateau pika, rat and mouse were analyzed and compared by using of bioinformatics software. The VEGF mRNA was detected by real-time PCR, and the MVDs in cerebral tissues of the plateau zokor, plateau pika and Sprague-Dawley (SD) rat were measured by immunohistochemical staining. The results showed that the open reading frame of the plateau zokor VEGF was 645 bp, and the coding sequence of the plateau zokor VEGF cDNA shared 92.1%, 93.6% and 93.8% nucleotide sequence homology to that of the plateau pika, rat and mouse, respectively. The deduced amino acid sequence of the plateau zokor VEGF cDNA was composed of 188 amino acids and the amino acids from 1 to 26 were signal peptide sequence. The plateau zokor VEGF188 was 90.2%, 94.9% and 94.4% homologous to that of plateau pika, rat and mouse. The level of VEGF mRNA in brain of the plateau zokor was significantly lower than that of SD rat, but there was no obvious difference in VEGF mRNA level between plateau zokor and plateau pika. The MVD in brain of the plateau zokor was markedly higher than that of plateau pika and SD rat. In conclusion, plateau zokor enhances its adaptation to the hypoxic environment by increasing the MVD. The level of VEGF mRNA in the brain of plateau zokor is lower than that of SD rat, which may be as a result of inhibition by the higher concentration of carbon dioxide in the burrow.

Role of c-Jun NH (2)-terminal kinase in insulin resistance after burn / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of c-Jun NH (2)-terminal kinase (JNk) in insulin resistance after burn and its mechanism.</p><p><b>METHODS</b>Twenty-four Sprague-Dawley rats were randomized to control, burn and burn + anisomycin groups. The rats in control group received sham burn trauma, and burn and burn + anisomycin groups received 30% total body surface area (TBSA) full thickness burn injury. Anisomycin (5 mg/kg) together with 250 microl dimethyl sulfoxide (DMSO) was injected to the rats in anisomycin group intravenously, and only 250 microl DMSO in the other two groups. Euglycemic-hyperinsulinemic glucose clamps was performed 2 hours after the injection. The changes of phospho-serine 307, phospho-tyrosine of insulin receptor substrate (IRS)-1 and phospho-JNK in muscle tissues were determined and compared using immunoprecipitation and Western blot analysis or immunohistochemistry in the three groups.</p><p><b>RESULTS</b>The infusing rates of total 10% glucose (mg x kg(-1) x min(-1)) in control, burn and burn + anisomycin group were 12.3 +/- 0.4, 6.6 +/- 0.3, 6.5 +/- 0.4, respectively. The level of IRS-1 Serine 307 phosphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn.</p><p><b>CONCLUSIONS</b>The activation of JNK elevates the level of IRS-1 phospho-serine 307 and might play a role in insulin resistance after burn in rats.</p>

Activation of nuclear factor-kappaB signaling pathway in rat gastric mucosa during stress ulceration / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the time course of nuclear factor-kappaB (NF-kappaB) activation in the process of stress ulcer formation.</p><p><b>METHODS</b>Model of stress ulcer was reproduced by subjecting male Sprague-Dawley rats to water-immersion restraint (WIR) stress. At indicated time after the beginning of WIR stress, animals were sacrificed and cytoplasmic and nuclear protein and total RNA were prepared from gastric corpus mucosal tissues. DNA-binding activity of NF-KB was assessed as an index of NF-kappaB activation with electrophoretic mobility shift assay. Degradation of IkappaBalpha and IkappaBbeta, the inhibitory proteins of NF-kappaB, was analyzed by Western blot analysis. Expression of NF-kappaB dependent genes including tumor necrosis factor-alpha (TNF-alpha) , interleukin-1beta (IL-1beta), cytokine-inducible neutrophil chemoattractant-1 ( CINC-1), intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase (iNOS) was detected with Northern blot analysis.</p><p><b>RESULTS</b>WIR stress induced a rapid biphasic activation of gastric mucosal NF-kappaB within 15 min of the beginning of stress, peaking at 45 min and 360 min. Compared with baseline, NF-kappaB activation by stress was increased (10.6 +/- 1.3) and (8.9 +/- 1.2) fold at 45 min and 360 min, respectively (P < 0.01). Antibody supershift assays revealed that p50/p65 heterodimer was the major active component of mucosal NF-kappaB. Western blot analysis showed that degradation of IkappaBalpha and IkappaBbeta occurred at first and second wave of NF-kappaB activation. Corresponding with the rapid and persistent activation of NF-kappaB, the levels of TNF-alpha, IL-1beta, CINC-1 and ICAM-1 mRNA in gastric mucosa were markedly increased 15 to 30 min after stress, respectively. Up-regulation of iNOS mRNAs was observed 30 to 90 min after stress, and the expression of all of these genes was increased consistently until the end of stress.</p><p><b>CONCLUSION</b>NF-kappaB activation is an early event and may play an important role in proinflammatory gene over-expression in rat gastric mucosa during WIR stress.</p>

Amelioration of insulin resistance after scald by c-Jun N-terminal kinase inhibitor in rat / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the role and mechanism of c-Jun N-terminal kinase (JNk) inhibitor (SP600125) in amelioration of insulin resistance after scald.</p><p><b>METHODS</b>Twenty-four Sprague-Dawley rats were randomized into sham (the process of scald was mimicked by water at room temperature) , scald, scald and SP600125 groups. The rats were inflicted with 30% TBSA full-thickness scald in the latter two groups. Euglycemic-hyperinsulinemic glucose clamp experiment was carried out 4 days after scald. SP600125 was administered to the rats in scald and SP600125 2 hrs before Euglycemic-hyperinsulinemic glucose clamp was performed. Changes in the phospho-Serine307 and phospho-tyrosine of IRS-1 activity, as well as expression of phospho-JNK in muscles were determined.</p><p><b>RESULTS</b>Euglycemic-Hyperinsulinemic Glucose Clamps experiment showed that the infusion rate of 100 g/L glucose in sham, scald, scald and SP600125 groups were (12. 33 +/-0. 42) , (6. 61 +/-0. 27) , (11. 11 +/-0. 68) mgx kg(-1) x min(-1) , respectively ( P <0.01). The level of IRS-1 Serine307 phosphorylation and JNK activity in muscles were significantly increased, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after scald. Compared with scald group, the level of IRS-1 Serine307 phosphorylation and JNK activity in scald and SP600125 group were decreased but tyrosine phosphorylation was elevated.</p><p><b>CONCLUSION</b>SP600125 can partially ameliorate insulin resistance after scald by inhibition of JNK activation, and decrease the level of IRS-1 phospho-serine307.</p>

Interaction between p38 mitogen-activated protein kinase signal transduction pathway and NF-kappaB/IkappaB system on the proinflammatory cytokines release after burn trauma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the interaction between p38 mitogen-activated protein kinase signal transduction pathway and nuclear factor (NF)-kappaB/IkappaB system on the proinflammatory cytokines release after burn trauma.</p><p><b>METHODS</b>Human monocyte line THP-1 were incubated with serum from eight healthy controls, burn sera, burn sera pretreatment with SB203580, and burn sera pretreatment with pyrrolidine dithiocarbamate (PDTC). After 24 hours incubation with serum, tumor necrosis factor (TNF)-alpha and interleukin-1beta (IL-1beta) levels in THP-1 culture supernatants were measured by ELISA. The activities of p38 MAPK and expressions of IkappaBalpha in THP-1 were measured by Western blot analysis. The EMSA method was used to characterize the binding activities of NF-kappaB and activating protein (AP)-1 in THP-1.</p><p><b>RESULTS</b>In comparison with normal controls, burn sera resulted in a significant higher level release of TNF-alpha and IL-1beta in THP-1 [(7.30 +/- 0.84) ng/ml vs (2.20 +/- 0.28) ng/ml, P < 0.05; (2.88 +/- 0.38) ng/ml vs (0.81 +/- 0.14) ng/ml, P < 0.05], which were significantly inhibited by pretreatment with SB203580 or PDTC. Burn sera showed increased activities of p38 MAPK and AP-1 in THP-1 (4728 +/- 582 vs 1291 +/- 163, P < 0.05; 946 +/- 137 vs 361 +/- 40, P < 0.05), which were abolished by pretreatment with SB203580 but not PDTC. The expression of IkappaBalpha in THP-1 incubated with burn sera was significantly decreased than those incubated with control sera (1211 +/- 115 vs 2658 +/- 318, P < 0.05), which were abolished by pretreatment with PDTC but not SB203580. Burn sera also leaded to an increased activity of NF-kappaB in THP-1 (1636 +/- 170 vs 317 +/- 32, P < 0.05), which were abolished by pretreatment with PDTC but not SB203580.</p><p><b>CONCLUSIONS</b>There are no direct interaction between p38 MAPK signal transduction pathway and NF-kappaB/IkappaB pathway. These two pathways, which regulate the production of TNF-alpha and IL-1beta in monocyte following burn trauma, are parallel and independent.</p>

Study on the changes in the distribution and chemical states of the hepatic intra-and extra-cellular sodium ion in the rats with severe burns at early stage / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the changes in the distribution and chemical states of the hepatic intra- and extra-cellular sodium ion in the rats with severe burns, so as to provide guidance for fluid resuscitation at early postburn stage.</p><p><b>METHODS</b>Nineteen adult male Sprague-Dawley (SD) rats were employed in the study and were randomly divided into control (n = 12) and burn (n = 7) groups. The changes in the longitudinal (T1) and transverse (T2) relaxation times of hepatic intra-cellular and extra-cellular sodium in the two groups were studied with 23Na NMR spectroscopy and a shift reagent.</p><p><b>RESULTS</b>After infusion of the shift reagent,the extra-cellular sodium content in rat liver decreased by 17%, with obvious increase in fast T2 component (P < 0.01), indicating an increase in the fraction of Na+ binding sites in the extra-cellular space. The characteristics of relaxation of intra-cellular sodium remained unchanged despite a 57% increment in intra-cellular sodium content.</p><p><b>CONCLUSION</b>The deficiency of sodium as a permeable molecule might be related to the postburn movement of hypertonic sodium from extra-cellular to intra-cellular space. The results indicated that it is reasonable to administer high concentration of sodium in fluid resuscitation during the first 24 postburn hours.</p>

The modulating role of p38 mitogen-activated protein kinase in the expression of tumor necrosis factor-alpha in hepatic cells and its role in hepatic injury in severely burned rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate The modulating role of p38 mitogen-activated protein kinase (MAPK) in the expression of tumor necrosis factor-alpha in hepatic cells and its role in hepatic injury in severely burned rats.</p><p><b>METHODS</b>Twenty-four adult healthy male SD rats were randomly divided into three groups (8 rats in each group): sham group, burn group, and burn with SB203580 group. A rat model of full-thickness burn injury covering 30% total body surface area (TBSA) was reproduced. The specific inhibitor of p38MAPK (SB203580 in 10 mg/kg) was given to the rats in the burn with SB203580 group at 15 minutes and 12 hours after burn. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured at 24 postburn hours (PBHs). The TNF-alpha mRNA expression in the liver was determined by real-time reverse transcription polymerase chain reaction, and the expression levels of p38MAPK and phosphor-p38MAPK in the liver were determined by Western blot analysis.</p><p><b>RESULTS</b>The serum levels of AST and ALT, and the expression of TNF-alpha mRNA in liver cells were significantly higher in burn group than those in sham and SB203580 groups (P < 0.05 or 0.01), but there was no difference between the two latter groups. It was indicated by Western blot results that there was no difference of p38MAPK expression in rat liver among the three groups (P > 0.05). The phospho-p38MAPK expression ratio among sham, burn and burn with SB203580 groups was 1.00:3.90:1.10. The phospho-p38MAPK expression was significantly lower in burn with SB203580 group than that in burn group (P < 0.01), but there was no significant difference compared with that in sham group (P > 0.05).</p><p><b>CONCLUSION</b>The postburn activated p38MAPK in rat liver after severe burn injury enhances the expression of TNF-alpha mRNA and participates in the development of postburn hepatic injury.</p>

Activation of p38 MAPK signal transduction pathway by burn serum and the expression of VCAM-1 in HUVECs induced by NF-kappaB / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the influence of burn serum on the expression of vascular cell adhesion molecule-1 (VCAM-1) of human umbilical vein endothelial cells (HUVECs) andits signal transduction mechanism.</p><p><b>METHODS</b>HUVECs cultured in vitro were employed for the experiment, and were divided into normal control (NC, with addition of normal serum), burn serum (BS, with addition of burn serum), SB203580 (with addition of 10 micromol/L SB203580 treatment 1 hour before burn serum treatment) and PDTC [with 10 mmol/L pyrrolidine dithiocarbamate (PDTC) 1 hour before burn serum treatment] groups. Protein and mRNA expression of VCAM-1 in HUVECs was measured by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) respectively at 0, 6, 12, 24 and 36 hours after burn serum treatment. The expression of VCAM-1 on HUVEC surface and the soluble VCAM-1 (sVCAM-1) content in HUVECs culture supernatants were measured by ELISA at 24 hours after the serum stimulation. Adherence of peripheral blood mononuclear leukocytes (PBMC) adherence to HUVECs was also observed in vitro.</p><p><b>RESULTS</b>The expression of VCAM-1 mRNA increased obviously in BS group after the burn serum stimulation and reached peak level at 24 post stimulation hour (PSH), and it decreased thereafter. The above expression was significantly decreased in SB203580 and PDTC groups at 24 PSH, but there was no difference compared with normal control (P > 0.05). The VCAM-1 expression on the membrane of HUVEC was evidently higher in BS group (66.5 +/- 6.2) than that in NC group (19.1 +/- 1.9, P < 0.05) at 24 PSH, but it was decreased significantly in SB203580 (21.7 +/- 2.3) and PDTC (23.1 +/- 2.4) groups and there was no significant difference compared with NC group (P > 0.05), and which was evidently lower than that in BS group (P < 0.05). The VCAM-1 content in the supernatant of BS group (125 +/- 10 ng/L) was obviously higher than that in NC (23 +/- 3 ng/L), SB203580 (27 +/- 5 ng/L) and PDTC (29 +/- 5 ng/L) groups. (P < 0.05). The number of PBMCs adherent to HUVECs in BS group [(197 +/- 11)%] was much larger than that in NC group [(100 +/- 4)%], SB203580 group [(113 +/- 7)%] or PDTC group [(97 +/- 112)%] at 24 PSH (P < 0.05), but no difference between NC group and SB203580, PDTC groups (P > 0.05).</p><p><b>CONCLUSION</b>Burn serum can enhance the expression of VCAM-1 in HUVECs through p38 MAPK signaling pathway, and the activation of NF-kappaB was also involved in this process.</p>

Role of p38 mitogen-activated protein kinase in the pathogenesis of stress ulcer / 中华外科杂志

<p><b>OBJECTIVE</b>To determine whether the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of stress ulcer.</p><p><b>METHODS</b>Model of stress ulcer was established with the treatment of rats with water-immersion restraint (WIR) stress. Ulcer index (UI) was macroscopically evaluated as a parameter of gastric mucosal lesions. Expression of phospho- and pan-p38 in gastric mucosa was detected using Western blot analysis. Tumor necrosis factor-alpha (TNF-alpha) and Interleukin 1beta (IL-1beta) gene expressions were analyzed by Northern blot analysis. As indicated in some experiments, rats were pretreated with intravenous injection of the specific p38 MAPK inhibitor CNI-1493 prior to WIR stress and then the changes of UI and TNF-alpha and IL-1beta mRNA expression were examined.</p><p><b>RESULTS</b>The p38 MAPK was persistently activated in the gastric mucosa of rats with WIR stress, with maximal activation after 1 h of stress [(6.8 +/- 3.2) fold of baseline levels, P < 0.01]. Inhibition of p38 MAPK activation with CNI-1493 led to a marked decrease in UI in WIR stress rats. Similarly, the increased gene expression of proinflammatory cytokines TNF-alpha and IL-1beta in gastric mucosa induced by WIR stress were significantly diminished by p38 MAPK inhibition.</p><p><b>CONCLUSION</b>p38 MAPK might have an important role in the pathogenesis of stress ulcer.</p>

Clinical investigation in the expression of matrix metalloproteinase 2 mRNA in the hyperplastic scar in burn patients / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the dynamic expression of matrix metalloproteinase 2 in the hyperplastic scar in burn patients.</p><p><b>METHODS</b>Twenty-three pieces of hyperplastic scar tissue samples were harvested from the patients with deep partial thickness burn wound during the early, middle and late periods after natural wound healing. In situ hybridization technique and positive cell percentage counting were employed to determine the expression and the distribution of MMP-2 mRNA in the scar tissue from different periods with that of the middle period as the control.</p><p><b>RESULTS</b>MMP-2 mRNA was mainly expressed in the fibroblasts in scar tissue. The positive percentage of MMP-2 in early period was 13.9 +/- 3.6%, and it increased thereafter, till it reached 68.7 +/- 5.2% in the middle period. However, it declined to 2.0 +/- 0.9% in the late period.</p><p><b>CONCLUSION</b>MMP-2 might be closely related to the process of scar tissue remodeling.</p>

Role of p38MAPK signal transduction pathway in Kupffer cells production of TNF-alpha and IL-1beta in severely burned rats / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the Kupffer cells production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in severely burns rats.</p><p><b>METHODS</b>Male health adult Sprague-Dawley rats were randomized into four groups: sham burn rats given vehicle, sham burn rats given the p38 MAP kinase inhibitor SB203580, rats given a 30% total body surface area (TBSA) full-thickness burn and fluid resuscitation plus vehicle, and burn rats given injury and fluid resuscitation plus SB203580. Rats from each group were killed at 24 h after burn or sham burn and Kupffer cells (KCs) were isolated. After 18 h incubation, KCs next were stimulated with 50 ng/ml of LPS for 18 h. After stimulation, supernatants were removed for analysis of TNF-alpha and IL-1beta levels by ELISA. The TNF-alpha and IL-1beta mRNA expressions (by quantitative real-time RT-PCR) and the activities of p38 MAPK and JNK (by Western blot analysis) in KCs were examined.</p><p><b>RESULTS</b>Eighteen hours after 50 ng/ml LPS stimulation, KCs from burn rats released significantly higher levels of TNF-alpha and IL-1beta than did shams. The mRNA levels of TNF-alpha and IL-1beta in KCs increased significantly postburn. Western blot analysis suggested that expression of phosphorylated p38 MAPK and JNK were increased in KCs harvested from burn group after stimulation with LPS compared with those from sham group. In vivo administration of SB203580 markedly suppressed both the release of TNF-alpha and IL-1beta and the mRNA expressions of TNF-alpha and IL-1beta in KCs from both sham and burn rats. p38 MAPK activity in KCs was abolished by administration with SB203580, whereas JNK was not.</p><p><b>CONCLUSIONS</b>p38 MAPK signal transduction pathway mediates KCs production of proinflammatory cytokines TNF-alpha and IL-1beta in severely burned rats.</p>

Role of p38 mitogen-activated protein kinase signal transduction pathway in the acute lung injury of severely burned rats / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the acute lung injury of severely burned rats.</p><p><b>METHODS</b>Forty-eight adult healthy rats were randomly divided into three groups: sham group, burn control group, and burn + SB203580 group. A third-degree burns over 30% total body surface area rat model was used and pulmonary capillary permeability, lung water content, pulmonary histology and p38 MAPK activity were measured at 24 hours postburn.</p><p><b>RESULTS</b>Burn trauma resulted in increased pulmonary capillary leakage permeability (42.5 +/- 4.7 vs. 12.1 +/- 1.4, P < 0.01), elevated lung water content (P < 0.05), and worsen histologic condition. There was a significant activation of p38 MAPK at 24 hours postburn compared with control. SB203580 inhibited the activation of p38 MAPK, reduced the pulmonary capillary leakage permeability (24.7 +/- 2.9 vs. 42.5 +/- 4.7, P < 0.01), decreased lung water content, and prevented burn-mediated lung injury.</p><p><b>CONCLUSION</b>The activation of p38 MAPK is one important aspect of the signaling event that contributes to burn-induced lung injury.</p>

Mechanism of p38 mitogen-activated protein kinase in postburn acute pulmonary injury in scalded rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the production of the proinflammatory factors such as tumor necrosis factor (TNF-alpha) and interleukin 1beta (IL-1beta) in lungs and in the pulmonary endothelial cell injury in severely scalded rats.</p><p><b>METHODS</b>Forty eight adult healthy SD rats were randomly divided into three groups with 16 rats in each group, i.e. sham, burn and burn with SB203580 treatment groups. The changes in the TNF-alpha and IL-1beta contents in serum and bronchoalveolar lavage fluid (BALF), the von Willebrand factor (vWF) contents in plasma and pulmonary microvessels and pulmonary activating protein (AP-1) activity were determined at 24 postburn hours (PBH).</p><p><b>RESULTS</b>Compared with those in sham group, the TNF-alpha and IL-1beta contents in serum and BALF and the vWF content in plasma (194.2% +/- 28.3% vs 93.2% +/- 14.3%) at 24 PBH in burn group increased significantly (P < 0.01), whereas vWF content in pulmonary microvessel decreased obviously (1.1 +/- 0.3 vs 3.3 +/- 0.4, P < 0.01). In addition, the pulmonary AP-1 activity also increased at 24 PBH. Nevertheless, all the above indices improved obviously in burn with SB203580 (inhibitor of p38 MAPK signal transduction pathway) treatment group when compared with those in burn group.</p><p><b>CONCLUSION</b>AP-1 might mediate the production of proinflammatory factors, such as TNF-alpha and IL-1beta in lungs leading to pulmonary vascular endothelial injury, after being activated by activated p38 MAPK.</p>

Study on the intra- and extra-hepatocyte distribution of sodium ions in scalded rats during early postburn stage / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of the intra- and extra-hepatocyte sodium ions distribution in scalded rats during early postburn stage,with the aim of improving burn shock resuscitation regime and the resuscitation effects.</p><p><b>METHODS</b>Adult Sprague-Dawley rats were randomly divided into sham scalding (C, n = 12) and scalding (S, n = 7) groups. The rats in S group were subjected to 40% TBSA III degree scalding on the back and were catheterized via jugular vein for fluid resuscitation. The rats in C group were catheterized via jugular vein without fluid infusion and were sham scalded by warm water in temperature of 37 degrees. The changes in the intra- and extra-hepatocyte sodium ion contents were determined in vivo by (23)Na-magnetic resonance spectrum technology, while the existing state of the intra- and extra-hepatocyte sodium ion was determined by detecting (23)Na-magnetic resonance horizontal delaying time (T(2)).</p><p><b>RESULTS</b>The extra-hepatocyte sodium content in S group at 24 postburn hours (PBHs) was 17% less than that in C group. In addition, the T(2f) (fast T(2)) in S group remained stable but maintained a higher ratio during the observation time. This suggested that the sodium binding sites in extra-hepatocyte matrix increased relatively and that intra-hepatocyte sodium content increased by 57%. But the T(2) and the fast and slow parts of the T(2) kept stable, which implied that intra-hepatocyte catabolizing products were increased. This led to an increase in the sodium ion binding sites within intra-hepatocyte matrix in proportion to the sodium ion content.</p><p><b>CONCLUSION</b>During early postburn stage, the extra-hepatocyte sodium in a remote organ such as the liver exhibited relative deficiency due to its ingress into hepatocyte cytoplasm and to the increase of sodium combining sites.</p>