Hypertonic saline resuscitation contributes to early accumulation of circulating myeloid-derived suppressor cells in a rat model of hemorrhagic shock / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hemorrhagic shock is usually associated with complicated immune and inflammatory responses, which are sometimes crucial for the prognosis. As regulators of the immune and inflammatory system; proliferation, migration, distribution and activation of myeloid-derived suppressor cells (MDSCs) are intimately linked to the inflammation cascade.</p><p><b>METHODS</b>In a model of severe hemorrhagic shock, thirty-five rats were randomly divided into control, sham, normal saline resuscitation (NS), hypertonic saline resuscitation (HTS), and hydroxyethyl starch resuscitation (HES), with seven in each group. MDSCs were analyzed by flow cytometric staining of CD11b/c(+)Gra(+) in peripheral blood mononuclear cells (PBMC), spleen cell suspensions, and bone marrow nucleated cells (BMNC). Simultaneously, the expressions of arginase-1 (ARG-1) and inducible nitric oxide synthase (iNOS) mRNA in MDSCs were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).</p><p><b>RESULTS</b>In the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the MDSCs in the PBMC of NS, HTS and HES groups markedly increased, and MDSCs in BMNC of these groups decreased accordingly, significantly different to the control group. In hemorrhagic shock rats infused with HTS at the early resuscitation stage, MDSCs in PBMC increased about 2 and 4 folds, and MDSCs in BMNC decreased about 1.3 and 1.6 folds, as compared to the sham group respectively, with statistically significant difference. Furthermore, compared to the NS and HES groups, the MDSCs in PBMC of HTS group increased 1.6 and 1.8 folds with statistically significant differences; the MDSCs decrease in BMNC was not significant. However, there was no statistically significant difference in MDSCs of spleen among the five groups. In addition, compared to the control, sham, NS and HES groups, the ARG-1 and iNOS mRNA of MDSCs in PBMC, spleen and BMNC in the HTS group had the highest level of expression, but no statistically significant differences were noted.</p><p><b>CONCLUSIONS</b>In this model of rat with severe and controlled hemorrhagic shock, small volume resuscitation with HTS contributes to dramatically early migration and redistribution of MDSCs from bone marrow to peripheral circulation, compared to resuscitation with NS or HES.</p>

Effect of hypertonic versus isotonic saline resuscitation on heme oxygenase-1 expression in visceral organs following hemorrhagic shock in rats / 生物医学与环境科学（英文）

To compare the early effects of hypertonic and isotonic saline resuscitation on heme oxygenase-1 (HO-1) expression in organs of rats with hemorrhagic shock. Rats were randomly divided into hypertonic saline resuscitation (HTS), normal saline resuscitation (NS) and sham groups. HO-1 mRNA, protein expression and apoptosis were evaluated in organs. In the HTS group, significant difference was noted in HO-1 protein in small intestinal mucosa and liver compared with the NS and sham groups, and in HO-1 mRNA in liver and kidney compared with the sham group. The apoptosis of small intestinal mucosa, liver, heart, and lung was significantly lower in the HTS group than that in the NS group. In this study, small volume resuscitation with HTS can efficiently up-regulate the expression level of HO-1 in small intestinal mucosa and liver, which may be one of the mechanisms alleviating organ damage.

Early changes of CD4⁺CD25⁺Foxp3⁺ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses. This study was conducted to investigate the early pathophysiological changes of CD4(+)CD25(+)Foxp3(+) Treg and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation.</p><p><b>METHODS</b>A rat model of controlled hemorrhagic shock with no fluid resuscitation was established. Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation. Three color flow cytometry was used to detect Tregs, Th1, Th2, Tc1 and Tc2 cells in the samples.</p><p><b>RESULTS</b>In the peripheral blood of rats, the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P = 0.001). The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08 ± 8.98)% to (23.91 ± 15.36)%, and from (40.40 ± 21.56)% to (65.48 ± 23.88)%, respectively.</p><p><b>CONCLUSIONS</b>At an early stage, the advent of hemorrhagic shock is related to an early decrease of Tregs, and a mild shift in the Th1/Th2, Tc1/Tc2 balance toward Th1 and Tc1 dominance. These changes are part of a hyper-inflammatory state of the host, and will deteriorate the maintenance of immune balance. Further influences and detailed mechanisms need to be investigated.</p>

Effect of hypertonic saline resuscitation on heme oxygenase-1 mRNA expression and apoptosis of the intestinal mucosa in a rat model of hemorrhagic shock / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Massive blood loss due to trauma is the leading cause of death in trauma patients and military combatants. The fluid category of resuscitation for hypotensive trauma patients is open to debate. This study was conducted to investigate the early effects of hypertonic and isotonic saline solutions on heme oxygenase-1 (HO-1) mRNA expression and apoptosis in the intestinal mucosa of rats with hemorrhagic shock.</p><p><b>METHODS</b>A model of severe hemorrhagic shock was established in 21 Sprague-Dawley rats. The rats were randomly divided into sham, normal saline resuscitation (NS), and hypertonic saline resuscitation (HTS) groups, with 7 in each group. We assessed and compared the HO-1 mRNA expression and apoptosis in the small intestinal mucosa of rats after hemorrhagic shock and resuscitation using the SYBR Green I fluorescence quantitative reverse transcriptase polymerase chain reaction, fluorescein-iso-thiocyanate-annexin V/propidium iodide double staining, and flow cytometry.</p><p><b>RESULTS</b>In the early stage of hemorrhagic shock and resuscitation, marked apoptosis occurred in the small intestinal mucosa from both the NS and HTS groups. The apoptotic rate in the NS group was higher than that in the HTS group (P < 0.01). Among the three groups, HO-1 mRNA mucosa from the HTS group had the highest level of expression; however, the differences were not significant. There was a significant negative correlation between HO-1 mRNA expression and apoptosis in the small intestinal mucosa from the NS and HTS groups after hemorrhagic shock and resuscitation.</p><p><b>CONCLUSIONS</b>In this rat model of severe hemorrhagic shock, HTS resuscitation with a small volume is more effective than NS resuscitation in reducing apoptosis of the intestinal mucosa. Further, HO-1 mRNA over-expression in the intestinal mucosa may be one of the molecular mechanisms of HTS in the resuscitation of hemorrhagic shock.</p>

Hypertonic saline resuscitation reduces apoptosis of intestinal mucosa in a rat model of hemorrhagic shock / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To investigate the early effects of hypertonic and isotonic saline solutions on apoptosis of intestinal mucosa in rats with hemorrhagic shock.</p><p><b>METHODS</b>A model of rat with severe hemorrhagic shock was established in 21 Sprague-Dawley (SD) rats. The rats were randomly divided into the sham group, normal saline resuscitation (NS) group, and hypertonic saline resuscitation (HTS) group, with 7 in each group. We detected and compared the apoptosis in small intestinal mucosa of rats after hemorrhagic shock and resuscitation by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), FITC (fluorescein-iso-thiocyanate)-Annexin V/PI (propidium iodide) double staining method, and flow cytometry.</p><p><b>RESULTS</b>In the early stage of hemorrhagic shock and resuscitation, marked apoptosis of small intestinal mucosa in the rats of both NS and HTS groups was observed. The numbers of apoptotic cells in these two groups were significantly greater than that in the sham group (P<0.01). In the HTS group, the apoptic cells significantly decreased, compared with the NS group (P<0.01).</p><p><b>CONCLUSION</b>In this rat model of severe hemorrhagic shock, the HTS resuscitation of small volume is more effective than the NS resuscitation in reducing apoptosis of intestinal mucosa in rats, which may improve the prognosis of trauma.</p>

Screening of carcinogenesis associated genes in gastric carcinoma by gene chip / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To screen the carcinogenesis associated genes in gastric carcinoma by gene chip.</p><p><b>METHODS</b>U133A (Affymetrix Santa Clara, CA) gene chip was used to detect differentially expressed genes in tumor tissues, paratumor mucosa and normal mucosa. Bioinformatics was used to analyze the screened results.</p><p><b>RESULTS</b>A total of 150 genes were detected with a difference of expression levels more than 3 times in paratumor mucosa compared with normal gastric mucosa, 130 of which were up-regulated and 20 down-regulated. According to the function classifications of the differentially expressed genes, the most common ones were enzyme and enzyme regulon activity associated genes(28, 18.7% ). The frequencies of nuclei acid binding activity associated genes,signal transduction associated genes and protein binding associated genes were 11.3%, 10%, and 8.7% respectively. Seventy-one differentially expressed genes were detected both in tumor tissues and paratumor mucosa compared with normal mucosa, 61 of which were up-regulated and 10 down-regulated. Among these 71 genes,e leven genes were localized on chromosome 19, 6 on chromosome 1, 2, 16, 17 respectively. No abnormal differentially expressed gene were detected on chromosome 5, 14, 22 and Y.</p><p><b>CONCLUSIONS</b>These 71 genes differentially expressed both in tumor tissues and paratumor mucosa may be associated with carcinogenesis of gastric carcinoma. The four kinds of genes associated with enzyme and enzyme regulon activity, nuclei acid binding activity, signal transduction, and protein binding should be the main genes for the study of carcinogenesis in gastric carcinoma.</p>

Study on gene expression profile difference in gastric cancer, pericancerous mucosa and normal gastric mucosa from the distant cutting margin by oligonucleotide microarray / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the difference of gene expression profiles in gastric cancer (T), pericancerous mucosa (P) and the gastric mucosa from distant cutting margin (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray.</p><p><b>METHODS</b>U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results.</p><p><b>RESULTS</b>When gastric cancer was compared with normal gastric mucosa, 766 genes were found,with a difference of more than four times in expression levels, including 530 up-regulated [Signal Log Ratio (SLR) > 2], and 236 down-regulated (SLR< -2). When P was compared with C, 64 genes were found, with a difference of more than four times in expression levels, including 50 up-regulated (SLR > 2), and 14 down-regulated (SLR< -2). Compared with C, a total of 143 genes with a difference of more than four times in expression levels both in T and P tissues. Of the 143 genes, 108 were up-regulated (SLR > 2), and 35 were down-regulated (SLR< -2).</p><p><b>CONCLUSIONS</b>Gene chip can reveal 143 same genes both in pericancerous mucosa and gastric mucosa. These genes may be related to the carcinogenesis and development of early gastric cancer.</p>