【Abstract】ObjectiveTo explore the mechanisms of anabolism intensified by recombination human growth hormone (GH) on the basis of total parenteral nutrition (TPN) during postoperative in gastrointestinal carcinoma patients. MethodsNinety-four gastrointestinal carcinoma patients undergone operation were randomly divided into TPN group and TPN+GH group. The levels of TNF-α, IL-1, IL-6 and CRP were detected in the first, third, seventh postoperative day. ResultsThe levels of TNF-α, IL-1, IL-6 and CRP were significantly lower in TPN+GH group than those in the TPN group at the first, third, seventh postoperative day （P＜0.01）. The levels of TNF-α, IL-1, IL-6 and CRP were significantly higher at the indicated time of postoperative days than the pre-operative days in the two groups (P＜0.01）. ConclusionBy inhibiting TNF-α, IL-1, IL-6 and CRP production in gastrointestinal carcinoma patients undergone operation and blocking high catabolism induced by inflammatory cytokines, GH promotes the synthesis of anabolism.
Objective To study the effect of nontypeable Hemophilus influenzae(NTHi) strain ATCC49247 on proinflammatory cytokines expression of human A549 lung epithelial cell line. Methods Confluent A549 cells were co-incubated with NTHi, NTHi+Erythromycin(10 mg/L), NTHi+Gentamicin(100 mg/L), and NTHi+Dexamethasone(100 μmol/L),and nuclear factor kappa B(NF-κB) inhibitor primed cells were co-incubated with NTHi for 24 h. Then levels of interleukin-8（IL-8） and tumor necrosis factor-α(TNF-α) in the supernatant was assayed by enzyme-linked immunosorbent assay(ELISA) and the expression of intercellular adhesion molecule-1(ICAM-1) in cells was detected by immunohistochemistry staining. Results A549 cells were transformed and died after co-intubated with NTHi for 24 h. NTHi induced A549 cells to release significantly greater amounts of IL-8, which was inhibited by NF-κB inhibitor pyrrolidine dithiocarbamate（PDTC）. Incubating of A549 cells with NTHi significantly induced release of IL-8 and the expression of ICAM-1, which was blocked by erythromycin and dexamethasone and not by gentamicin. TNF-α was not detected in all circumstances. Conclusions NTHi can increase significantly the release and expression of proinflammatory cytokines through NF-κB pathway. Antibacterial drug erythromycin also has anti-inflammatory effect.
Objective To investigate the changes and significance of serum inflammatory factors in coronary heart disease ( CHD) patients with obstructive sleep apnea-hypopnea syndrome ( OSAHS) , and the treatment effects of continuous positive airway pressure( CPAP) . Methods A total of 76 CHD patients in Renmin Hospital of Wuhan University from October 2007 to October 2008 were enrolled. Polysomnography ( PSG) was performed in these CHD patients to identify if they were complicated by OSAHS. The levels of inflammatory factors including TNF-α, IL-6, high sensitive C-reactive protein ( hs-CRP) in serum were determined in the CHD patients and 23 normal subjects. The CHD patients with moderate-severe OSAHS ( AHI≥15 episodes/hour) were treated by Auto-CPAP for 3 months and all parameters above were measured again. Results There were 41 /76 ( 53. 9% ) of CHD patients had moderate-severe OSAHS and were treated with CPAP. The levels of TNF-α, IL-6 and hs-CRP were significantly higher in the CHD patients than those in the normal controls ( all P lt; 0. 01) , and were significantly higher in moderate-severe OSAHS patients than those in the non-OSAHS CHD patients. Auto-CPAP ventilation significantly decreased the levels of inflammatory factors in the CHD patients with moderate-severe OSAHS. Conclusions An obvious proinflammatory state is detected in CHD patients, and is aggravated with OSAHS. CPAP is a useful treatment for CHD patients with mediate to severe OSAHS.
Objective To observe the changes of soluble triggering receptor expressed on myeloid cell-1 ( sTREM-1) and inflammatory mediators levels in plasma of severe pneumonia patients, and explore the significance of systemic inflammatory response state.Methods Plasma levels of sTREM-1, tumor necrosis factor-α ( TNF-α) and interleukin-10 ( IL-10) were examined in 40 patients with severe pneumonia, 25 patients with uncomplicated pneumonia, and 15 healthy volunteers. Plasma levels of TNF-α,IL-10 and sTREM-1 in survival and non-survival severe pneumoniawere observed on days 1,4, 7 and the day of discharge or death.Results Plasma levels of TNF-α, IL-10, and sTREM-1 [ ( 44. 25 ±10. 81) pg/mL,( 58. 21 ±16. 41) pg/mL, ( 51. 75 ±18. 51) pg/mL, respectively] in the patients with severe pneumonia were higher than those with uncomplicated pneumonia [ ( 24.6 ±6. 45) pg/mL, ( 24. 56 ±7. 1) pg/mL,( 25. 55 ±7. 72) pg/mL, respectively] and the normal controls [ ( 13. 82 ±4. 04) pg/mL, ( 15. 30 ±4. 45)pg/mL, ( 14. 37 ±4. 82) pg/mL, respectively] ( P lt;0. 001) . Plasma levels of TNF-α, IL-10, and sTREM-1 were gradually decreased in the survivors, while maintained at high levels or increased in the non-survivors.The levels of these mediators were all significantly higher in the non-survivors than the survivors at all time points. The ratio of TNF-α/ IL-10 level was higher in the severe pneumonia patients than the uncomplicated pneumonia patients and the control subjects ( 1. 286 ±0. 177 vs. 1. 077 ±0. 410 and 0. 932 ±0. 154) on day 1.The ratio of TNF-α/IL-10 level was higher in the non-survivors than the survivors at all time points. There was negative correlation between plasma levels of sTREM-1 and TNF-αon day 1 ( r = - 0. 479, P =0. 002) ,and positive correlation between plasma levels of sTREM-1 and IL-10 on day 1 ( r = 0. 326, P = 0. 040) .Conclusions There are excessive release of inflammatory mediators and unbalanced systemic inflammatory response in patients with severe pneumonia, especially in non-survivors. sTREM-1, TNF-α and IL-10 are involved in the inflammatory response, and their levels may reflect the prognosis.
Objective To identify the effects of single immunoglobin IL-1 receptor related protein （SIGIRR） on inflammation induced by high mobility group box 1 （HMGB1） in A549 derived from human alveolar epithelial cells. Methods Eukaryotic expression vectors pCDNA3.1（+） constructed with SIGIRR cDNA were transiently transfected into A549 cells，in which SIGIRR was forced to be over-expressed. Western blot and RT-PCR were applied to detect the expression level of SIGIRR after transfection. After the stimulation by HMGB1，the transcriptional activity of NF-κB in A549 cells was detected by dual-luciferase reporter assay system，and the protein levels of inflammatory cytokine TNF-α and IL-1β were measured by ELISA. Results The expression level of SIGIRR increased significantly in A549 cells transfected with SIGIRR vectors. The transcriptional activity of NF-κB was enhanced obviously after HMGB1 treatment in A549 cells by dual-luciferase reporter assay system，while the transfection of SIGIRR vectors decreased the activity. The protein levels of TNF-α and IL-1β were down-regulated in A549 cells over-expressing SIGIRR after HMGB1 stimulation compared with the non-transfected cells. Conclusions Up-regulated SIGIRR expression can inhibit HMGB1-induced proinlammatory cytokine release in A549 cells such as TNF-α and IL-1β. The transcriptional activity of NF-κB is dampened by SIGIRR transfection，implying that the anti-inflammatory effects of SIGIRR may be involved in the regulation of NF-κB.
Objective To explore the role of macrophage-stimulating protein ( MSP) and receptor tyrosine kinase RON in the airway inflammation of chronic obstructive pulmonary disease( COPD) , and investigate its possible mechanism. Methods The rat COPDmodel was established by exposing the rats to cigarette smoke daily for three months. Rat alveolar macrophages ( AMs) were isolated in vivo and cultured,and then challenged with different concentrations of MSP for 24 hours. The concentrations of MSP in broncho-alveolar lavage fluid ( BALF) and serum, and the levels of IL-1β, TNF-α, IL-8, and IL-10 in the supernatants were measured by ELISA. The expression of RONmRNA in lung tissue was assessed by reverse transcription-polymerase chain reaction. The levels of RON protein in the lung tissue and AMs cultured in vitro were observed by immunohistochemistry. The activity of superoxide dismutase ( SOD) and malondialdehyde ( MDA) content in the culture solution were measured with chromatometry method. Results Compared with the control group, the concentrations of MSP in serum and BALF of the COPD rats were significantly higher ( P lt;0. 01) . The levels of RONmRNA and RON protein in the COPD rats were also upregulated significantly ( P lt; 0. 01) . MSP evoked the AMs isolated from the normal and COPD rats to generate more content of MDA and caused a reduction in activity of SOD. In addition, MSP stimulated TNF-α, IL-8, IL-1βand IL-10 release fromAMs of the normal and COPD rats dose-dependently. The levels of TNF-α, IL-8, and IL-1βwere higher, while the level of IL-10 and the SOD activity were lower in AMs of the COPD group than those of the control group in the same dose of MSP ( P lt;0. 01) . The more significant increase in the levels of TNF-α, IL-8, IL-1β, and the more notable decrease in the activity of SOD was found in the COPD group compared with the control group. But the degree of increasing MDA and IL-10 in the AMs of the COPD group was lower than that in the control group. Linear correlation analysis showed that the MSP concentration and the RON protein level in the COPD rats were positively associated with the total cellcounts and AM counts in BALF, and were related to the indexes for pulmonary emphysema. Conclusions There is a close correlation between the MSP and receptor tyrosine kinase RON with the airway inflammation of COPD. The mechanism might be that MSP promote the macrophages release inflammatory factors and increase the production of oxygen free radicals.
目的 探讨慢性阻塞性肺疾病（COPD）患者中微量元素铜和锌与炎症介质的关系。 方法 2010年11月－2011年3月间测量15例COPD急性加重期患者入院时及治疗后和13例健康者为对照组的血清铜、锌、C反应蛋白（CRP）、白介素-6（IL-6），血浆中金属硫蛋白，以及氧化应激产物丙二醛的浓度变化。并对铜、锌浓度变化与CRP、IL-6进行相关分析。 结果 COPD组血清中铜浓度、CRP、IL-6水平高于对照组（P＜0.05），同时急性加重期患者血清中铜的浓度、CRP、IL-6水平以及丙二醛值高于缓解期患者（P＜0.05）。而急性加重期患者血清中锌浓度低于缓解期组和对照组（P＜0.05）。血浆中抗氧化物质金属硫蛋白在三组间差异无统计学意义（P＞0.05）。在微量元素与炎症因子的相关分析中发现，铜与CRP（r=0.602，P＜0.001）、IL-6（r=0.533，P＜0.001）呈正相关，锌与IL-6呈负相关（r=?0.336，P＜0.05）。 结论 在COPD氧化应激发病机制中，铜可能发挥促氧化应激的作用，而锌可能发挥抗氧化应激的作用。微量元素稳态的紊乱有可能是COPD急性加重的危险因素。
Objective To investgate the expression of p38 mitogen-activated protein kinase （p38MAPK） in lung tissue of rats with severe acute pancreatitis （SAP）， and to explore the relationship between p38MAPK and pulmonary capillary barrier injury. Methods Forty male and healthy Sprague-Dawley （SD） rats were randomly （random number method） divided into sham operation （SO） group and SAP group， then rats of SAP group were sub-divided into 3， 6， 12， and 24 h group， each group enrolled 8 rats， respectively. SAP model rats were established by injecting 5% sodium taurocholate solution retrograde into the biliopancreatic duct. ELISA method was used to test the serum tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and pathological changes in lung and pancreas tissues were observed by HE staining. Immunohischemistry method was used to detect phosphorylated p38 （p-p38） protein and aquaporin 1 （AQP1） protein of lung tissues. The expression level of AQP1 mRNA was measured by quantitative real-time PCR. Results Hyperemia， edema， and inflammatory cell infiltration were observed in lung tissues， abundance of necrosis， part gland structure fuzzy or even disappear were observed in pancreas tissues of all 4 time point groups. Compared with SO group， levels of serum TNF-α and IL-1β were significantly higher in 4 time point groups （P＜0.05）. Lower expression level of p-p38 protein was detected in lung tissues of SO group， while in the early stage of SAP （SAP 3 h group）， the expression level of p-p38 protein significantly increased， which peaked in 6 h group and was still higher than SO group in 24 h group （P＜0.05）. Compared with SO group， the expression levels of AQP1 mRNA and protein were significantly lower in all 4 time point groups （P＜0.05）， which had negative correlation with the levels of serum TNF-α，IL-1β， and the expression level of p-p38 protein （r=-0.87， P＜0.05；r=-0.88， P＜0.05；r=-0.78， P＜0.05）. Conclusion The decrease of AQP1 protein in lung tissue is one of the vital causes for pulmonary capillary barrier injury in SAP， which probably works by the activation of p38MAPK and the excessive release of inflammatory cytokines.
Objective To study the effect of interleukin-6,10 (IL-6,10), C-reactive protein (CRP), and fibrinogen (FIB) on inflammatory response of lower limbs deep vein thrombosis (DVT). Methods Thirty patients with acute lower limb DVT (DVT group) and 30 volunteers (normal control group) were included in this study, and then the concentrations of serum IL-6, IL-10, CRP, and FIB were detected. Results The concentrations of serum IL-6, IL-10, CRP, and FIB of patients in DVT group before treatment were higher than those in normal control group (Plt;0.001). Compared with before treatment, the concentrations of serum IL-6, CRP, and FIB of patients after treatment were lower in DVT group (Plt;0.001), however, the concentration of serum IL-10 was higher (Plt;0.001). There was no difference of the concentrations of serum FIB between DVT group after treatment and normal control group (Pgt;0.05), but the concentrations of serum IL-6, IL-10, and CRP of patients in DVT group after treatment were higher than those in normal control group (Plt;0.05). Conclusion Inflammatory factors may involve in DVT. Therein IL-6, CRP, and FIB play important roles in acute stage of DVT, and IL-10 may have an anti-inflammatory effect.
Objective To investigate the influence of proteasome inhibitorMG-132 on inflammatory factors in COPD rats and its potential mechanism. Methods The COPD rat model was established by instillation of lipopolysaccharide and exposure to cigarette smoke. Then the rats were randomly divided into 4 groups( n = 12 in each group) , ie. a COPD model group, a COPD + MG-132 low concentration group ( 0. 05 mg·kg- 1·d - 1 ) , a COPD + MG-132 high concentration group( 0. 1 mg· kg- 1 · d - 1 ) , and a normal control group. The rats were injected intraperitoneally with different dose of MG-132 or normal saline. After 1 week and 4 weeks, 6 rats in each group were sarcrificed. Then the following parameters were determined including histopathological changes of lung tissue, and the concentrations of IL-1β, IL-6, IL-8 in serum and diaphragm via ELISA. Results The lung histopathological examination showed obvious emphysema and inflammatory infiltration in the COPD rats. These pathological changes were obviously ameliorated in two MG-132 treatment groups. The IL-1β, IL-6, and IL-8 levels in serumand diaphragmin the COPD model group were all significantly increased from1 week and 4 week than those in the normal control group( P lt;0. 05) .MG-132 down-regulated the expression of these inflammatory factors in a time-and dosedependent manner. The IL-1β, IL-6, and IL-8 levels in serum and diaphragm in the MG-132 low concentration group and high concentration group were all decreased compared with the COPD model group ( P lt; 0. 05) . Conclusion COPD is a systemic inflammatory disease which can be inhibited by the proteasome inhibitor MG-132 through suppressing inflammatory factors.