Abstract： Objective To explore the feasibility of using protamine-agarose gel to achieve heparin-free cardiopulmonary bypass （CPB）. Methods A total of 12 healthy adult dogs were chosen, the dogs were between 2-3 years old,either male or female, with their mean body weight of 23.3±3.7 kg （ranging from 20 to 28 kg）. All the dogs were randomly divided into two groups with 6 dogs in each group. In the heparinized group, conventional CPB technique was used; in the non-heparinized group, protamine-agarose gel column was used to absorb plasma clotting factors in CPB without use of heparin. At the beginning of CPB and 1 h, 2 h, 3 h after CPB, arterial blood samples were collected from dogs in both groups. The expression levels of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and interleukin-8 （IL-8） were measured by enzyme-linked immunosorbent assay（ELISA）and compared. Results There was no thrombus formation in the membrane oxygenators during CPB by naked eye observation in both groups. Activated coagulation time （ACT） was always greater than 480 s during CPB. The vital signs of the dogs were all stable during CPB. At the beginning of CPB, there was no statistical difference in plasma concentrations of TNF-α, IL-6, IL-8 between the two groups. At 1 h, 2 h and 3 h after CPB, the expression levels of TNF-α and IL-8 of the non-heparinized group were significantly higher than those of the heparinized group （CPB 3 h TNF-α：156.48±16.65 ng/L vs. 115.87±15.63 ng/L, t=4.356, P=0.001；CPB 3 h IL-8：365.38±46.18 ng/L vs. 299.29±34.50 ng/L, t=2.808, P=0.019）. There was no statistical difference in the expression level of IL-6 between the two groups （P＞0.05）. Conclusion Using protamine-agarose gel to absorb plasma clotting factors is an effective technique to establish heparin-free CPB. But this method can induce significant systemic inflammatory response.
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.
ObjectiveTo isolate and identify the cartilage progenitor cells (CPCs) from normal cartilage, and to explore the influence of interleukin 1β (IL-1β) in different concentrations on its chondrogenesis. MethodsCPCs were isolated from normal cartilage of adult New Zealand white rabbit with the fibronectin adhesion assay;the cell phenotype was identified;and the cloning and differentiation of CPCs were observed. CPCs were incubated with H-DMEM in group A, with chondrogenic induced medium in group B, with chondrogenic induced medium+0.1 ng/mL IL-1β in group C and chondrogenic induced medium+1.0 ng/mL IL-1β in group D for 3 weeks. The histology, biochemistry, and real-time fluorescence quantitative PCR were performed to observe the effect of IL-1β on the chondrgenic differentiation. ResultsThe CPCs from normal cartilage expressed positively stem cell phenotype, which have similar ability of cloning and differentiation to stem cells. The cell pellets in groups C and D were significantly smaller than those in group B, and cell showed hypertrophic morphology change. There were more expressions of collagen type Ⅱ and collagen type X in group B than in group A, in group B than in groups C and D, and in group C than group D with Safranin O staining. The biochemistry results showed that collagen type Ⅱ content, glycosaminoglycan (GAG) content, and the ratio of GAG/DNA were significantly lower in groups C and D than in group B (P<0.05), and in group D than in group C (P<0.05);but the DNA content was significantly higher in groups C and D than in group B (P<0.05), and no significant difference between groups C and D (P>0.05). The real-time fluorescence quantitative PCR results showed that the relative mRNA expressions of collagen type Ⅱ, collagen type X, and Sox-9 were significantly lower in groups C and D than in group B (P<0.05), and in group D than in group C (P<0.05), but the relative mRNA expressions of Runx-2 and matrix metalloproteinase 13 were significantly higher in groups C and D than in group B (P<0.05), and in group D than in group C (P<0.05). ConclusionThere are CPCs having the character of stem cells in normal cartilage, and they have the capability of cloning and potential differentiation. IL-1β can inhibit the chondrogenesis of CPCs, and possibly promote the osteogenic differentiation.
ObjectiveTo explore the effects of simvastatin on the expression of matrix metalloproteinase (MMP) and inflammatory factors in rats with smoke-induced chronic obstructive pulmonary disease (COPD). Methods40 male Wistar rats were randomly divided into four groups, including a normal group (group A), a simvastatin group (group B), a COPD model group (group C) and a simvastatin intervention group (group D). The COPD model of the group C and D were induced through exposing to the cigarette smoke repeatedly. At the same time, the rats of group B and D were given by gavage 5 mg/(kg·d) with simvastatin, and the other two groups were given with the same volume saline for 16 weeks. Pulmonary function tests and pathological examination of the lung tissue were performed after the induction of COPD model. Enzyme-linked immunosorbent assay (ELISA) method was used to measure the content of MMP-2, MMP-9, IL-6, IL-8, TNF-α in lung tissue homogenate. ResultsThe airway resistance of group C and group D was significantly higher than the group A and group B (P<0.01), and the airway resistance of group D was significantly lower than group C (P<0.01). The degree of bronchial inflammation and emphysema of group C was more apparent than group D in the pathological section, and there were no bronchial inflammation and emphysema in group A and group B. The ELISA results showed that the contents of MMP-2, MMP-9, IL-6, IL-8, TNF-α in group C were all significantly higher than those in group D. ConclusionSimvastatin has inhibitory effect on pulmonary inflammation of COPD, and can reduce the expression of matrix metalloproteinase and inflammatory factors in the lung.
ObjectiveTo explore the levels of serum leptin,TNF-α,IL-8 and hypersensitivity C-reactive protein (hs-CRP) in stable COPD patients with different body mass index (BMI). Methods30 healthy controls with BMI 18.5 to 23.9 kg/m2 and 105 patients with stable COPD were recruited in the study. The serum levels of leptin,TNF-α,and IL-8 were determined by radioimmunoassay and hs-CRP level was determined by versatile biochemical automatic analyzer. The COPD patients were divided into a low BMI group (BMI<18.5 kg/m2,n=32),a normal BMI group (BMI 18.5-23.9 kg/m2,n=48),and a high BMI group (BMI≥23.9 kg/m2,n=25). ResultsSerum leptin level in the COPD patients was significantly reduced compared with the control subjects (P<0.05). Serum leptin levels were reduced in the low BMI and the high BMI groups compare with the normal BMI group [(7.89±3.16)ng/L and (10.52±5.98)ng/L vs. (13.04±5.73) ng/L,P<0.01 or P<0.05]. Leptin level in the low BMI group was lower than that in the high BMI group (P<0.05). Serum TNF-α levels were significantly increased in the low BMI group compared with the normal BMI and high BMI groups [(229.39±89.57)μg/L vs. (180.06±74.24) μg/L and (189.46±82.41) μg/L,P<0.01]. Serum TNF-α level in the COPD patients was significantly increased compared with the control subjects [(192.37±83.65) μg/L vs. (178.59±60.38) μg/L,P<0.05]. The IL-8 levels were not significant different among three BMI groups with COPD. The hs-CRP level in the high BMI group was higher than that in the low BMI and normal BMI groups (P<0.05). ConclusionLeptin and TNF-α may be involved in weight-loss of COPD malnutritional patients.
ObjectiveTo systematically review the influence of dexmedetomidine on early postoperative cognitive dysfunction (POCD) and serum inflammatory factors in elderly patients.MethodsWe searched PubMed, EMbase, The Cochrane Library, CBM, CNKI, WanFang Data and VIP databases from inception to April 2017, to collect randomized controlled trials (RCTs) about dexmedetomidine for early POCD in elderly patients. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed by RevMan 5.3 software.ResultsA total of 23 RCTs, including 2 026 patients were enrolled. The results of meta-analysis showed that, the incidence of POCD in the dexmedetomidine group was lower than that in the control group (the first day: RR=0.40, 95%CI 0.30 to 0.53, P<0.000 01; the third day: RR=0.33, 95%CI 0.23 to 0.48,P<0.000 01; the seventh day: RR=0.42, 95%CI 0.22 to 0.78,P=0.006). Meanwhile, compared with the control group, the dexmedetomidine group significantly decreased the serum levels of TNF-α (immediately after operation: MD=–5.43, 95%CI –7.44 to –3.42, P<0.000 01; 1 h after operation: MD=–4.64, 95%CI –6.92 to –2.36,P<0.000 1; 24 h after operation: MD=–3.27, 95%CI –4.92 to –1.63,P<0.000 1) and IL-6 (immediately after operation: MD=–30.69, 95%CI –41.39 to –20.00,P<0.000 01; 1h after operation: MD=–20.84, 95%CI –28.87 to –12.80,P<0.000 01; 24 h after operation: MD=–13.42, 95%CI –19.90 to –6.94,P<0.000 1).ConclusionCurrent evidence indicates that dexmedetomidine could relief early POCD in elderly patients, in which the reduction of serum inflammatory factors alleviate inflammation response may play a vital role. Due to the limited quality and quantity of included studies, more high quality RCTs are required to verify the above conclusion.
ObjectiveTo systematically review the data of peripheral inflammatory markers in patients with Alzheimer’s disease (AD) and vascular dementia (VaD) to further indicate pathogenesis and antidiastole.MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect studies on peripheral inflammatory markers in patients with AD and VaD from inception to July 2020. Two reviewers independently screened literature, extracted data, and assessed risk of bias of included studies, and meta-analysis was performed by using Stata 15.1SE software.ResultsA total of 30 studies involving 2 377 patients were included. The results of meta-analysis showed that the IL-6 level was higher in VaD group than that in AD group (SMD=−0.477, 95%CI −0.944 to −0.009, P=0.046). However, there were no statistical difference in peripheral IL-1β (SMD=−0.034, 95%CI −0.325 to 0.257, P=0.818), TNF-α (SMD=0.409, 95%CI −0.152 to 0.970, P=0.153) or CRP (SMD=0.277, 95%CI −0.228 to 0.782, P=0.282) levels.ConclusionsThese findings suggest that IL-6 may be sensitive markers to distinguish AD from VaD. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the conclusions.
ObjectiveTo summarize the clinical usage of modified ultrafiltration in pediatric cardiopulmonary bypass. MethodsWe selected 40 infants with congenital heart defects as our study subjects between January 2010 and February 2012. They were randomly divided into two groups. One group used modified ultrafiltration, while the other did not, during the operation with cardiopulmonary bypass. The different perioperative changes of pulmonary pressure and the tumor necrosis factor (TNF) and interleukin-8 (IL-8) concentration in plasma were observed in both the two groups. ResultsNo complication relative to modified ultrafiltration was found. After the operations began, TNF and IL-8 concentration in the two groups rose fast; at the end of operations and 2 hours after operation, the pulmonary pressure and TNF and IL-8 concentration in the two groups decreased, and the decrease in the modified ultrafiltration group was faster. ConclusionThe use of modified ultrafiltration during operations with cardiopulmonary bypass can reduce residual water within the body in a short period and decrease the concentration of inflammatory factors, which is helpful for postoperative recovery of the cardiac and lung functions.
ObjectiveTo investigate the changes of interleukin-8 (IL-8), tumor necrosis factor-α(TNF-α) and phospholipase A2 (PLA2) in serum, bronchoalveolar lavage fluid (BALF) and lung tissue of COPD rats and the effects of tiotropium.To identify the anti-inflammatory function of tiotropium. MethodsRat COPD model was established by passive smoking as well as intratracheal instillation of lipopolysaccharide(LPS).Thirty male SD rats were randomly divided into a control group, a COPD group and a tiotropium bromide treatment group (n=10 in each group).The pathologic changes of the lung tissue and airway were observed by HE staining.The total and differential cell counts in BALF were observed.The levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue were measured by enzyme-linked immunosorbent assay. ResultsHE staining revealed that the rat COPD model was successfully established.The COPD group appeared obvious emphysema, while the treatment group appeared mild emphysema.The total inflammatory cells, the proportion of neutrophils and lymphocyte, and the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue in the COPD group were obviously higher than those in the control group (P < 0.01).The total inflammatory cells, the proportion of neutrophils and lymphocyte, and the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue in the treatment group were significantly lower than those in the COPD group but higher than those in the control group (P < 0.01). ConclusionsTiotropium bromide can reduce the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue of COPD rats by reducing the leakage of inflammatory cells, and alleviate the airway inflammation and the degree of emphysema.
ObjectiveTo bioinformatically analyze the gene chip data of chondrocytes from osteoarthritis patients from the Gene Expression Omnibus (GEO) database, and explore the molecular mechanisms of osteoarthritis.MethodsWe searched the GEO database (up to April 23rd, 2021) for data of chondrocytes and gene expression profiling in human knee osteoarthritis via the key words of “osteoarthritis OR cartilage OR chondrocyte*”. Then, we selected the samples by our inclusion criteria. The data were normalized before analysis. After differentially expressed genes were identified, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Search Tool for the Retrival of Interacting Genes/Proteinsm, R language, Perl language, Cytoscape software, and DAVID database were used to perform differentially expressed gene analysis, functional annotation, and enrichment analysis.ResultsThe differentially expressed genes were mostly enriched in cell components and some extracellular regions, which participated in cell division, mitosis, cell proliferation and inflammatory response mainly via the regulation of protein kinase activity. The differentially expressed genes were mainly involved in the cell proliferation signaling pathway, mitogen-activated protein kinase signaling pathway, oocyte meiosis, cell cycle and so on.ConclusionsMultiple signaling pathways are involved in the changes of chondrocytes in human knee osteoarthritis, mainly about cell cycle and protein metabolism genes/pathways. Inflammatory factors and cytokines may be the most important links in the pathogenesis of osteoarthritis.