The activation of EGFR promotes myocardial tumor necrosis factor-α production and cardiac failure in endotoxemia.

To study the effect of EGFR activation on the generation of TNF-α and the occurrence of cardiac dysfuncetion during sepsis, PD168393 and erlotinib (both are EGFR inhibitors) were applied to decreased the production of TNF-α and phosphrylation of ERK1/2 and p38 induced by LPS in cardiomyocytes. These results were further proved by specifically knocked down the expression of EGFR in vitro. Both TAPI-1, a TNF-α converting enzyme (TACE) inhibitor, and TGF-α neutralizing antibody could inhibit the activation of EGFR and the generation of TNF-α mRNA after LPS treatment. The increase of TGF-α in response to LPS could also be suppressed by TAPI-1. On the other hand, exogenous TGF-α increased the expression of TNF-α mRNA and partially reversed the inhibitory effect of TAPI-1 on expression of TNF-α mRNA in response to LPS indicating that the transactivation of EGFR by LPS in cardiomyocytes needs the help of TACE and TGF-α. In endotoxemic mice, inhibition the activation of EGFR not only decreased TNF-α production in the myocardium but also improved left ventricular pump function and ameliorated cardiac dysfunction and ultimately improved survival rate. All these results provided a new insight of how EGFR regulation the production of TNF-α in cardiomyocytes and a potential new target for the treatment of cardiac dysfunction in sepsis.

Comparison of Pain Thresholds and Analgesic Effects of Parecoxib Sodium in Surgical Patients of Different Racial and Religious Backgrounds.

OBJECTIVE: To explore the differences of the thresholds of pain and analgesic effects of parecoxib sodium among patients with different racial and religious backgrounds. METHODS: A total of 48 male patients aged 18 to 38 years who had undergone elective laparoscopic appendectomy under general anesthesia in our centers were enrolled in our study and then divided into 6 groups(n=8 in each group)based on their racial backgrounds(three levels:Mongoloid,Negroid,and Europoid)and religious backgrounds(two levels:without religion background,with religion background).All subjects received the same anesthesia,surgical procedure,and postoperative analgesia with parecoxib sodium. The temperature pain threshold and electrical pain threshold were detected 1h before and after analgesia. RESULTS: The threshold of pain was higher in Europoids than in Negroids and Mongoloids before and after treatment. The temperature pain threshold and electrical pain threshold were not significantly different between subjects with or without religious background(before analgesic therapy:F=251.119,P=0.130,F=275.861,P=0.059;after analgesic therapy:F=308.531,P=0.086,F=180.062,P=0.078). Also,there was no interaction between the racial and religious backgrous in terms of temperature pain threshold and electrical pain threshold(F=13.553,P=0.091,F=22.001,P= 0.089;after analgesic therapy:F=4.624,P=0.089,F=15.935,P=0.094). CONCLUSIONS: The threshold of pain differs among individuals with different racial background:it is highest in Europoids,followed by Negroids and Mongoloids. It shows no obvious difference in people with different religious backgrounds.

Propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARγ/LXRα signaling pathway in THP-1 macrophage-derived foam cells.

BACKGROUND: ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor-B1 (SR-B1) promote cholesterol efflux from cells to lipid-poor apolipoprotein A-I and play an important role in the development of atherosclerosis. Liver X receptor (LXRα) and peroxisome proliferator-activated receptor-gamma (PPARγ) operate as cholesterol sensors, which may protect from cholesterol overload by stimulating cholesterol efflux from cells to high-density lipoprotein through ABCA1, ABCG1, and SR-B1. Propofol administration is associated with cardiovascular protective effects, including anti-inflammatory and antioxidant properties. Here, we examined the effect of propofol on ABCA1, ABCG1, and SR-B1 expression and explored whether PPARγ and LXRα were involved in the regulation of propofol-induced ABCA1, ABCG1, and SR-B1 expression in THP-1 macrophage-derived foam cells. METHODS AND RESULTS: Propofol significantly increased expression levels of ABCA1, ABCG1, and SR-B1 in a time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by propofol treatment. Moreover, PPARγ and LXRα were up-regulated by propofol treatment. In addition, the up-regulated expression of ABCA1, ABCG1, and SR-B1 by propofol was significantly abolished by both PPARγ siRNA and LXRα siRNA in THP-1 macrophage-derived foam cells. CONCLUSION: These results provide evidence that propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARγ/LXRα pathway in THP-1 macrophage-derived foam cells.

Propofol Attenuates Lipopolysaccharide-Induced Monocyte Chemoattractant Protein-1 Production Through Enhancing apoM and foxa2 Expression in HepG2 Cells.

Monocyte chemoattractant protein-1 (MCP-1) is a cytokine that mediates the influx of cells to sites of inflammation. Our group recently reported that propofol exerted an anti-inflammatory effect and could inhibit lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines. However, the effect and possible mechanisms of propofol on MCP-1 expression remain unclear. LPS-stimulated HepG2 cells were treated with 50 µM propofol for 0, 6, 12, and 24 h, respectively. The transcript and protein levels were measured by real-time quantitative PCR and Western blot analyses, respectively. We found that propofol markedly decreased both MCP-1 messenger RNA (mRNA) and protein levels in LPS-stimulated HepG2 cells in a time-dependent manner. Expression of apolipoprotein M (apoM) and forkhead box protein A2 (foxa2) was increased by propofol treatment in HepG2 cells. In addition, the inhibitory effect of propofol on MCP-1 expression was significantly abolished by small interfering RNA against apoM and foxa2 in LPS-stimulated HepG2 cells. Propofol attenuates LPS-induced MCP-1 production through enhancing apoM and foxa2 expression in HepG2 cells.

Short-term intensive atorvastatin therapy improves endothelial function partly via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase pathway in hyperlipidemic rabbits.

BACKGROUND: Atherosclerosis is a kind of disease with multiple risk factors, of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and development. The aim of this study was to determine the effects of short-term intensive atorvastatin (IA) therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short-term intensive statin therapy. METHODS: After exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively, treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent vasorelaxation function were, respectively, measured. mRNA and protein expression of CRP, TNF-α, IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5-lipoxygenase (5-LO) were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes. RESULTS: HFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction, including imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage infiltration into adipose tissue. Five-day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET-1; and improve endothelial function and macrophage infiltration without significant changes in blood lipids. However, all of the above were not observed in LA therapy. In vitro experiment found that lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5-LO in cultured adipocytes, which could be attenuated by short-time (6 hours) treatment of high-dose (5 µmol/L) but not low-dose (0.5 µmol/L) atorvastatin. In addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC, a potent and direct 5-LO inhibitor) could significantly downregulate the above-mentioned gene expression in LPS-treated adipocytes. CONCLUSION: Short-term IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, which may be partly due to attenuating inflammation of PCAT through inhibiting 5-LO pathway.

WITHDRAWN: Propofol reduces MMPs expression by inhibiting PI3K/AKT activity in human HepG2 cells.

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Propofol promotes proliferation of cultured adult rat hippocampal neural stem cells.

BACKGROUND: The effect of propofol on proliferation of adult neural stem cells (ANSCs) is unclear. We investigated the effect of propofol on cultured rat ANSCs and the underlying molecular mechanisms, especially the role of activated cAMP response element binding protein (CREB). METHODS: Rat ANSCs were treated with propofol at concentrations of 0 (control), 10, 50, or 100 µM, or with a DMSO vehicle. The cell viability was checked by cell counting and MTT assay. The proportions of BrdU-positive cells and pyknotic nuclei were also checked. Caspase activity was measured by a colorimetric assay. Cytoplasmic [Ca] were determined with Fura2-AM. The expression of CREB and phospho-CREB in cells was examined by immunostaining and Western blot. The role of p-CREB in cell proliferation was confirmed by using KN93, an inhibitor of p-CREB formation. RESULTS: Propofol promoted the proliferation of ANSCs (P<0.01) and increased the proportion of BrdU-positive cells (P<0.01). Cell death was maintained at a low level (P=0.0691) and inhibition of caspase-3 activity with propofol was not significant (P=0.0839). Propofol elevated the cytoplasmic-free calcium concentrations in ANSCs (P=0.0057). CREB and phospho-CREB were generally expressed in ANSCs with or without application of propofol. Propofol upregulated the phosphorylation level of CREB in ANSCs (P=0.0074). Application of KN93 diminished the proliferative effects of propofol and p-CREB levels (P<0.01) without disturbance of intracellular [Ca] (P=0.0722). CONCLUSIONS: Propofol acts partly through a Ca-mediated pathway to enhance CREB phosphorylation. We believe this mechanism promotes the in vitro proliferation of ANSCs.

C-reactive protein promotes vascular endothelial dysfunction partly via activating adipose tissue inflammation in hyperlipidemic rabbits.

BACKGROUND: Endothelial dysfunction is the basic and original sign of atherogenesis. Some evidences show that C-reactive protein (CRP) and perivascular adipose tissue (PVAT) play a pivotal role in atherosclerosis. However, the effects of CRP on atherosclerosis and the related mechanisms require elucidation. METHODS: The levels of basic total cholesterol, low-density lipoprotein cholesterol, triglyceride, CRP, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO) and endothelin-1 (ET-1) were respectively measured in rabbits, endothelium-dependent vasorelaxation function was also evaluated. Animals were randomly divided into two groups: PVAT(-) and PVAT(+) group (removing or keeping pericarotid adipose tissue (PCAT)). Both of the two groups were exposed to a high-fat diet for six-week, and then sustained CRP treatment was performed for a week, at this time point all the above parameters were remeasured. In addition, mRNA and protein expression of TNF-α, IL-6, and macrophage chemoattractant protein-1 (MCP-1) were respectively evaluated by Polymerase Chain Reaction and immunoblotting in PCAT and cultured adipocytes treated by CRP. RESULTS: High-fat diet greatly increased the serum lipids and inflammatory markers, induced endothelial dysfunction and imbalance between NO and ET-1, increased mRNA and protein expression of TNF-α, IL-6, MCP-1 and enhanced macrophage infiltration of PCAT. CRP treatment could further promote macrophage infiltration of PVAT, induce the imbalance between NO and ET-1, aggravate endothelial dysfunction especially in PVAT(+) arteries, and could also enhance the above-mentioned mRNA and protein expression in PCAT and cultured adipocytes. CONCLUSIONS: CRP could significantly promote endothelial dysfunction in high-fat diet rabbits especially in PVAT(+) groups, which may be partly mediated by activating inflammatory reaction of adipose tissue.

Anti-inflammatory effects of propofol are mediated by apolipoprotein M in a hepatocyte nuclear factor-1α-dependent manner.

Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous hypnotic agent in daily practice. However, its anti-inflammatory properties have seldom been addressed. In this study, we evaluated the anti-inflammatory activity and mechanisms of propofol on lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro and found that propofol markedly inhibited LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, and expression of inducible nitric oxide synthase (iNOS). At the same time, the expression of hepatocyte nuclear factor-1α (HNF-1α) and apolipoprotein M (APOM) was inhibited by treatment with LPS and LPS-induced down-regulation of HNF-1α expression and APOM expression could be compensated by propofol treatment. However, propofol could not compensate LPS-induced down-regulation of APOM expression by treatment with HNF-1α siRNA and the suppressive effect on LPS-induced pro-inflammatory cytokines production by propofol was significantly compensated by treatment with APOM siRNA. These results provide evidence that propofol may first up-regulate APOM expression by enhancing HNF-1α expression and then inhibit pro-inflammatory cytokine production in LPS-stimulated cells. Therefore, our study may be useful in understanding the critical effect of propofol in patients with systemic inflammatory response syndrome.

Propofol induces rat embryonic neural stem cell apoptosis by activating both extrinsic and intrinsic pathways.

Propofol has previously been shown to have detrimental effects on the developing brain. Neural stem cells, identified in the embryonic brain as well as in the adult brain, are multipotent, self-renewing cells, which are capable of differentiating into different phenotypes of the nervous system. The present study was designed to investigate propofol-induced rat embryonic neural stem cell apoptosis and its potential mechanisms. Rat embryonic neural stem cells were isolated, cultured and characterized. Treatment of these cultured stem cells with different doses of propofol was carried out and cell proliferation was assessed by MTT assay and apoptosis by flow cytometric analysis. Cellular levels of active forms of caspase-3 and caspase-8, which regulate the extrinsic apoptotic pathway, and of caspase-9 and cytochrome C, which regulate the intrinsic apoptotic pathway, were detected by western blotting. Over 95% of isolated rat embryonic neural stem cells expressed the Nestin protein, as detected by immunofluorescence staining. Using an in vitro cell culture system, we showed that propofol inhibited cell growth and induced cell apoptosis in a dose-dependent manner. Furthermore, western blot analysis showed that propofol treatment significantly elevated levels of active forms of caspase-3, caspase-8, caspase-9 and cytochrome C in the embryonic neural stem cells. Propofol induced rat embryonic neural stem cell apoptosis and activated caspase-3, caspase-8, caspase-9 and cytochrome C, suggesting that propofol-induced stem cell apoptosis may be regulated through both the extrinsic and intrinsic apoptotic pathways.

[GAT-1 and GAD65 mRNA expressions in different brain regions in dogs at brain propofol uptake equilibrium].

OBJECTIVE: To investigate the expressions of gamma aminobutyric acid transporter 1 (GAT-1) and glutamate decarboxylase 65 (GAD65) mRNA in different brain regions at brain propofol uptake equilibrium in dogs. METHODS: Eighteen 12- to 18-month-old healthy hybrid dogs were randomized equally into control group (group C), low dose group (group L), and high dose group (group H). In groups L and H, anesthesia was administered by intravenous injection of 5.5 and 7.0 mg/kg propofol followed by propofol infusion at a constant rate of 55 and 70 mg·kg(-1)·h(-1) for 50 min, respectively. Blood samples were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations, and the brain tissues of the hypothalamus, sub thalamus, dorsal thalamus, hippocampus, pons, parietal lobe and frontal lobe were examined for GAT-1 and GAD65 mRNA expressions using quantitative real-time PCR. RESULTS: In groups L and H, propofol infusion at a constant rate for 50 min resulted in comparable plasma propofol concentrations between the internal carotid artery and jugular vein (P>0.05), but the concentrations differed significantly between the two groups (P<0.01). GAT-1 mRNA levels in the hypothalamus and hippocampus were significantly higher in groups L and H than in group C (P<0.05 and P<0.01), but comparable between the former two groups. The variations of GAT-1 mRNA levels between the hypothalamus and hippocampus were similar in both group L [(61.26∓7.17)% and (79.34∓39.95)%, P>0.05] and group H [(74.64∓19.63)% and (97.12∓32.31)%, P>0.05]. GAT-1 mRNA levels in other brain regions showed no significant difference among the 3 groups. GAD65 mRNA levels were similar between group L and group H, but both significantly higher than that in group C (P<0.01). GAD65 mRNA in other brain regions had no significant difference among the 3 groups. CONCLUSION: GAT-1 mRNA in the hypothalamus and hippocampus and GAD65 mRNA in the dorsal thalamus are upregulated when propofol uptake reaches an equilibrium in the brain of dogs.

Penehyclidine enhances the efficacy of tropisetron in prevention of PONV following gynecological laparoscopic surgery.

PURPOSE: Postoperative nausea and vomiting (PONV) are common complications after gynecological laparoscopic surgery. Because monotherapy with antiemetics is insufficient, combinations of various antiemetics are often recommended by experts. In this study, our purpose was to find out whether penehyclidine could enhance the efficacy of tropisetron in preventing PONV. METHODS: With hospital ethics committee approval, we investigated 120 women undergoing gynecological laparoscopic surgery receiving prophylactic tropisetron (0.1 mg/kg; maximal dose, 5 mg) (group T) or tropisetron (0.1 mg/kg; maximal dose, 5 mg) plus penehyclidine (0.01 mg/kg; maximal dose, 1 mg) (group TP), or penehyclidine (0.01 mg/kg; maximal dose, 1 mg) (group P). The incidence of vomiting, the intensity of nausea (assessed by a visual analogue scale [VAS]), antiemetic rescues, and adverse effects were recorded at 2, 6, 12, and 24 h after surgery in the gynecological ward by a visiting nurse anesthetist who was unaware of the treatments. Collected data were analyzed using analysis of variance (ANOVA) and the χ(2) test. Continuous variables were expressed as means ± SD, and non-continuous variables were expressed as n (%). RESULTS: The overall incidence of vomiting was 28.3 % (34/120) in our study. The incidence of vomiting was significantly lower in group TP (4 cases, 10 %) than that in group T (12 cases, 30 %) and group P (18 cases, 45 %). The incidence of vomiting in group TP was also significantly lower than that in group T at 0-2 h and 2-6 h postoperatively and it was also significantly lower than that in group P at 0-2 h, 2-6 h, 6-12 h, and 12-24 h postoperatively. The incidence of vomiting was significantly lower in group T than that in group P at 12-24 h postoperatively. The VAS of nausea was significantly lower in group TP than that in group T and group P at 2 and 6 h after surgery. It also showed a significant higher score in group P than that at group T and group TP at 12 and 24 h. Within group P, the VAS of nausea was significantly lower at 2 h postoperatively than that at 24 h. CONCLUSIONS: Penehyclidine showed less efficacy in preventing PONV than tropisetron; however, compared with tropisetron or penehyclidine monotherapy, prophylactic medication with tropisetron plus penehyclidine significantly reduced the incidence of vomiting and decreased the intensity of nausea in women undergoing gynecological laparoscopic surgery.

[Effect of propofol at uptake equilibrium on γ-aminobutyric acid in different cerebral regions in dogs].

OBJECTIVE: To investigate the effect of propofol at doses for different anesthesia depths on γ-aminobutyric acid (GABA) in different cerebral regions at propofol uptake equilibrium in dogs. METHODS: Twelve 12-18-month-old healthy hybrid dogs weighing 10-12 kg were randomly divided into light anesthesia group (n=6) and deep anesthesia group (n=6) with a single bolus dose of propofol (5.5 and 7.0 mg/kg, respectively) completed in 15 s followed by intravenous propofol infusion at a constant rate (55 and 70 mg·kg(-1)·h(-1), respectively). Blood samples (2 ml) were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations 50 min after the start of the infusion. The dogs were then sacrificed and tissues were taken from different brain regions and the cervical cord to measure GABA concentrations using high-pressure liquid chromatography (HPLC). RESULTS: The plasma propofol concentrations in internal carotid artery and jugular vein were similar in both light anesthesia group (3.00 ± 0.31 and 3.10 ± 0.51 µg/ml, respectively, P>0.05) and deep anesthesia group (6.41 ± 0.05 and 6.40 ± 0.11 µg/ml, respectively, P>0.05). GABA concentrations in the brain regions were significantly higher in deep anesthesia group than in light anesthesia group (P<0.05). The dorsal thalamus and hypothalamus showed greater GABA variations [(83.83 ± 2.230%) and (85.83 ± 1.72)%] compared to other brain regions at different anesthesia depths (P<0.05). CONCLUSIONS: In both groups, plasma propofol concentrations in the internal carotid artery and internal jugular vein reach equilibrium at 50 min of propofol infusion. The variation of GABA is associated with the anesthesia depth of propofol, and GABA variation in the dorsal thalamus and hypothalamus plays an important role in propofol anesthesia.

Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway.

PURPOSE: Sevoflurane is used widely during lung cancer surgery. However, the effect of sevoflurane on the invasion and migration of lung carcinoma cells remains unclear. The aims of this study were to explore the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the effect of sevofluane on the invasion and the role of fascin and ezrin on the effect of sevofluane on the migration of human lung adenocarcinoma A549 cells. We also investigated whether sevoflurane regulates the expression of these molecules through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. METHODS: The invasion of cells was evaluated using the Transwell invasion assay, and the migration of cells was determined using the wound healing assay. The expression of MMP-2, MMP-9, ezrin, fascin, and phospho-p38 MAPK in cells was determined by western blotting. RESULTS: A significant inhibition of cell invasion and migration was found in A549 cells which had been treated with sevoflurane. The data also revealed that sevoflurane could decrease the phosphorylation level of p38 MAPK, which is involved in the downregulation of MMP-2, MMP-9, fascin, and ezrin expression, accompanied by a concomitant inhibition of the invasion and migration of A549 cells. SB203580, a p38 MAPK inhibitor, augmented the downregulation of the expression of these proteins. CONCLUSION: The anti-invasion effect of sevoflurane on A549 cells was associated with a downregulation of both MMP-2 and MMP-9 expression, while the anti-migration effect was associated with a downregulation of both fascin and ezrin expression. These effects could occur partly as a result of inactivation of the p38 MAPK signaling pathway.

A prospective randomized study of intraoperative thoracic epidural analgesia in off-pump coronary artery bypass surgery.

OBJECTIVE: The purpose of this study was to test the hypothesis that general anesthesia (GA) plus thoracic epidural anesthesia (TEA) has no impact on the outcomes of off-pump coronary artery bypass surgery (OPCABs) compared to GA followed by patient-controlled TEA (PCTEA), while GA plus TEA leads to a higher requirement for vasoactive drug use. METHODS: Sixty-four patients, American Society of Anesthesiologists physical status II and III, who were scheduled for elective OPCABs, were offered an epidural catheter inserted at the T2-3 interspace and then randomized into 1 of 2 groups according to whether TEA was applied intraoperatively. The TEA(perio) group received GA plus TEA, while the TEA(post) group received GA alone. All groups had postoperative PCTEA. The number of requirements for vasoactive drugs and the extubation times were recorded. The analgesic effect was monitored by visual analog scale (VAS) pain scores. Heart rate, blood pressure, and blood gases were also monitored. The data are presented as mean values ± standard deviation, or medians with quartiles. RESULTS: The proportion of vasoactive drug use was significantly higher in the TEA(perio) group intraoperatively (before or during completion of anastomoses: 59.4 vs. 20.7%, p = 0.004; after completion of anastomoses: 53.1 vs. 17.2%, p = 0.007). There was no statistically significant difference in extubation times or VAS scores between the 2 groups. CONCLUSIONS: We conclude that GA plus TEA has no impact on the outcomes of OPCABs, while its use leads to a higher requirement for vasoactive drug use. GA followed by PCTEA facilitates the anesthesia administration, while it does not affect the extubation time and the postoperative analgesic effect.

Hypertonic/hyperoncotic solution attenuate blood-brain barrier breakdown and brain pathology in whole body hyperthermia rats.

This study was designed to investigate the effects of hypertonic/hyperoncotic solution on blood-brain barrier damage, brain edema and morphological changes of rats during whole body hyperthermia. 90 adult male Sprague-Dawley rats were randomized into 5 groups: Control group (a room temperature for 4 hours); Whole body hyperthermia group without solution treatment; Whole body hyperthermia group with Ringer's solution treatment; Whole body hyperthermia group with hydroxyethyl starch and Ringer's solution treatment; Whole body hyperthermia group with Hypertonic/hyperoncotic solution treatment. All rats except those of control group were housed in a heated container and maintained at 36°C for 3 hours until the rectal temperature reached 41-42°C. Corresponding solutions were administered intravenously at the beginning of whole body hyperthermia within 30 minutes as designed. Following whole body hyperthermia, rats were subsequently cooled down for 1h. Evans blue was administered intravenously when the rectal temperature was cooled down to 37°C. The leakage of Evans blue-albumin and water content of brain were calculated and morphological changes were investigated. In group with hypertonic/hyperoncotic solution treatment, brain water content and the leakage of Evans blue-albumin were the lowest among the four whole body hyperthermia groups. Compared with the other three whole body hyperthermia groups, in which profound to moderate damages to blood-brain barrier and brain tissue and cells were found, there were only slight morphological changes in the group with hypertonic/hyperoncotic solutionon treatment. Treatment with hypertonic/hyperoncotic solution appeared to attenuate the injury to blood-brain barrier and reduce brain edema and cell morphological changes in whole body hyperthermia rats.

[Effects of hypertonic sodium chloride hydroxyethyl starch 40 on brain histopathology in rats with whole body hyperthermia].

OBJECTIVE: To investigate the effects of hypertonic sodium chloride hydroxyethyl starch 40 (HSH) on brain edema and morphological changes during whole body hyperthermia (WBH) in rats. METHODS: Sixty adult male SD rats were randomized into control group, WBH group without fluid infusion (group HT), WBH group with Ringer's infusion (group RL), WBH group with HAES + Ringer's infusion (group HRL) and WBH group with HSH infusion (group HSH). WBH was induced by exposure to 36 degrees celsius; for 3 h to achieve a rectal temperature of 41-42 degrees celsius;, and the corresponding fluids were administered intravenously within 30 min at the beginning of WBH. The control rats were housed at a controlled room temperature (22∓1) degrees celsius; for 4 h. After cooling at room temperature for 1 h, the rats were sacrificed and brain water content and morphological changes were evaluated. RESULTS: Compared with the control group, all the WBH groups had significantly increased brain water content (P<0.05 or 0.01), but group HSH showed a significantly lower brain water content than group HT (P<0.05). The rats in groups HT, RL and HRL showed serious to moderate structural changes of the brain tissue and nerve cells, but HSH group had only mild pathologies. CONCLUSION: HSH can reduce brain edema and ameliorate the damages to brain cells in rats exposed to WBH.

Propofol inhibits the activation of p38 through up-regulating the expression of annexin A1 to exert its anti-inflammation effect.

Inflammatory response is a kind of nonspecific immune response, with the central link of vascular response, which is mainly manifested by changes in neutrophils and vascular endothelial cells. In recent years, the in vivo and in vitro role of intravenous anesthetic propofol in inhibiting inflammatory response has been attracting more and more attention, but the anti-inflammatory mechanisms of propofol for mononuclear cells still remain undefined. In this study, proteomics analysis was applied to investigate protein expression profile changes in serum mononuclear cells following intervention of rats with endotoxemia using propofol. After two-dimensional electrophoresis and mass spectrometric identification, it has been found that the protein Annexin A1 was up-regulated in the propofol intervention group. Annexin A1 is a glucocorticoid-dependent anti-inflammatory protein. After detection using ELISA and Western blot assays, it has also been found that propofol can not only promote the expression of Annexin A1, but also inhibit the phosphorylation level of p38 and release of inflammatory factors (IL-1ß, IL-6 and TNF-α) in rats with endotoxemia. In order to further determine the role of up-regulated expression of Annexin A1 in anti-inflammation of propofol, this gene was silenced in vitro in human THP-1 cells, to detect the phosphorylation status of p38 and release of inflammatory factors. The results show that Annexin A1 can negatively regulate phosphorylation of p38 and release of IL-1ß, IL-6 and TNF-α in THP-1 cells following propofol intervention and lipopolysaccharide (LPS) stimulation. Our results clearly indicate that propofol can up-regulate Annexin A1 to inhibit the phosphorylation level of p38 and release of IL-1ß, IL-6 and TNF-α, so as to inhibit inflammatory response. Therefore, it can be speculated that Annexin A1 might be the key signaling protein in the in vivo and in vitro anti-inflammatory mechanisms of propofol.

[Effect of methylprednisolone pretreatment on pulmonary permeability and dipalmitoylphosphatidylcholine content in rabbits with reexpansion pulmonary edema].

OBJECTIVE: To investigate the effects of methylprednisolone pretreatment on pulmonary lung permeability index and the content of the pulmonary surfactant dipalmitoylphosphatidylcholine (DPPC) in a rabbit model of reexpansion pulmonary edema. METHODS: Twenty-one male New Zealand white rabbits were randomly divided into control group, reexpansion, and reexpansion+methylprednisolone pretreatment groups. The rabbit model of reexpansion pulmonary edema was established using Sakaos method. A bolus dosage of methylprednisolone (3 mg/kg) in reexpansion+methylprednisolone group group or 2.0 ml/kg normal saline in the other two groups was administered intravenously 20 min before reexpansion pulmonary edema. Bronchoalveolar lavage fluid (BALF) and arterial blood samples were collected for measurement of the total protein (TP) and DPPC contents 4 h after reexpansion, and the pulmonary permeability index was calculated. RESULTS: The pulmonary permeability index in methylprednisolone pretreatment group was significantly lower than that in the reexpansion group (0.007∓0.002 vs 0.177∓0.004, P<0.05). Methylprednisolone pretreatment significantly increased DPPC concentration in the BALF as compared with saline treatment in the reexpansion group (61.815∓28.307 vs 101.955∓24.544 µg/ml, P<0.05). CONCLUSION: Methylprednisolone pretreatment can increase pulmonary surfactant content and improve pulmonary permeability in the rabbit model of reexpansion pulmonary edema.