Objective To investigate the effect of aerosolized perfluorocarbon (PFC) (FC77) on gas exchange，histopathological changes of lung in acute lung injury and pulmonary expression of tumor necrosis factor-α (TNF-α) mRNA.Methods After acute lung injury (ALI) was induced by oleic acid (OA)，16 rabbits were assigned randomly into 2 groups,ie.aerosolized perfluorocarbon group (PFC group) and conventional mechanical ventilation group (CMV group).Gas exchange parameters were measured before and after ALI，at 1，2，3，4 h after treatment.Histological sections taken from 6 different parts of lung were stained by hematoxylin and eosion.The express of TNF-α mRNA in the 2 different parts of lung were detected by in situ hybridization (ISH).Results Compared with CMV group，the PaO2 and static lung compliance (CLst) were significantly increased (Plt;0.05)，the histopathological lesions of lung were attenuated，and the TNF-α mRNA expression was decreased significantly in PFC group (all Plt;0.05).There was more expression of TNF-α mRNA in backside than that in foreside of lung in two groups (Plt;0.05).Conclusion Aerosolized perfluorocarbon (PFC) can decrease expression of tumor necrosis factor-α mRNA in the lung，and improve the CLst and oxygenation during acute lung injury.
Purpose To investigate the expression of the interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-alpha;) in epiretinal membranes(ERM) of eyes with proliferative vitreoretinopathy(PVR). Methods Nineteen epiretinal membranes were obtained form eyes undergoing vitrectomy for retinal detachment complicated with PVR and observed by immunohistochemical methods. Results Expression of IL-6 and TNF-alpha; were observed in 12 and 15 membranes respectively with positive staining mostly in extracellular matrix of epiretinal membranes.Only one membrane showed positive to IL-6 intracellularly,and expression for IL-6 and TNF-alpha; simultaneously in membranes. Conclusion The findings indicate that IL-6、and TNF-alpha;might be involved in the development of PVR. (Chin J Ocul Fundus Dis,1998,14:219-221)
Objective To investigate the mechanism of dexamethasone in the treatment of acute necrotizing pancreatitis (ANP). Methods The ANP of 48 SD rats were induced by retrograde infusion of sodium taurocholate through biliopancreatic duct.After 30 minutes,the therapy group was administrated with dexamethasone at a dose of 0.2 mg/100 g alone. The control group was administrated with the same amount of 0.9% saline solution.At fourth hour and twelfth hour,8 rats of each group were sacrificed to examine the levels of serum tumor necrosis factor-alpha(TNFα) and serum amylase,to score the degree of pancreatic necrosis and to evaluate acinar cell apoptosis by in situ hybridization by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL). The survial period of 8 rats in each group were observed. Results In therapy group, the level of TNFα was (17.8±2.7) pg/ml and (8.5±1.6) pg/ml,the apoptosis index was （36.94±4.12）% and （ 32.79±3.31）%,the survival period was (33.4±21.5) h.While the control group with the indexes mentioned above were as follows: (53.6±18.7) pg/ml and (37.2±11.1) pg/ml ( P＜0.01),（4.37±1.24）% and （5.12±2.11）% （P＜0.01）,(14.6±5.7) h (P＜0.01) ,the histologic scoring for ANP between therapy group and control group was a significantly distinct (P＜0.01). Conclusion Dexamethasone can induce pancreatic acinar cell apoptosis in this model. Proper leves of TNFα may play an important role in regulating the apoptosis.Apoptosis can protect pancreas from necrosis in ANP.
ObjectiveTo observe the expression of vascular endothelial growth inhibitor (VEGI, TL1A), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in diabetes rats' serum, vitreous and retina, and discuss the role of VEGI in the pathogenesis of diabetic retinopathy (DR). MethodsA total of p70 adult male Wistar rats were randomly divided into 4 groups, the control group (10 rats), the diabetes mellitus (DM) 1 month group (20 rats), the DM 3 month group (20 rats) and the DM 6 month group (20 rats). Cytokines of serum and vitreous were determined by enzyme-linked immunosorbent assay (ELISA), and the concentrations of the cytokines in the retina were determined by immunohistochemistry on paraffin retinal sections. Hematoxylin-eosin (HE) staining of retina was used to estimate the pathological change of DR. The results were analyzed by one-way analysis of variances, independent samples t-test and LSD test. ResultsThe serum TL1A levels of the control group, the DM 1 month group, the DM 3 month group and the DM 6 month group rats were (92.09±2.05), (118.36±8.30), (85.90±7.51) and (78.90±4.88) ng/L respectively, the level of TL1A in serum of the DM 1 month group, the DM 3 month group and the DM 6 month group were significantly lower than that of the control group (F=77.405, P < 0.05). The concentration of serum TNF-α and IL-1β increased after DM model was established (F=3.508, 15.416; P < 0.05); the VEGF level in serum showed no difference between the groups (F=1.242, P > 0.05). The vitreous TL1A levels of the control group, the DM 1 month group, the DM 3 month group and the DM 6 month group were (91.50±8.18), (67.03±6.74), (47.44±4.92) and (46.01±4.62) ng/L respectively, every DM groups showed significant difference with the control group (F=114.777, P < 0.05); VEGF level in vitreous increased from 1 month after DM model was established (F=8.816, P < 0.05); TNF-α and IL-1β level in vitreous also showed an upward tendency (F=4.392, 3.635; P < 0.05). Paraffin section immunohistochemistry showed that the absorbance (also called optical density) of TL1A of the DM 1 month group and the DM 3 month group were significantly lower than that of the control group (t=6.851, 6.066; P < 0.05), but the DM 6 month group showed no difference with the control group (t=1.401, P > 0.05); the level of VEGF and TNF-α in DM groups were higher than that of the control group (tVEGF=-4.709, -16.406, -9.228; tTNF-α=-4.703, -6.583, -17.762; P < 0.05); the level of IL-1β were significantly higher in the DM 1 month group and the DM 6 month group (t=-4.108, -3.495; P > 0.05); but the DM 3 month showed no difference with the control group (t=-0.997, P > 0.05). HE staining of retina showed that the retina of the control group and the DM 1 month group had normal retinal structures, the DM 3 month group had retinal edema and disorganization, the DM 6 month group had severe retinal edema, deep stain of ganglion cells, and more neovascularization in inner plexiform layer. ConclusionVEGI is involved in the pathogenesis of DR, and it might interacts with VEGF, TNF-α and IL-1β to affect the development of DR.
Objective To examine the levels of interferon-gamma; (INF-gamma;), tumor necrosis factor-alpha; (TNF-alpha;) and interleukin-6(IL-6) in serum of patients with acute uveitis before and after treatment, and to explore the possible roles of those cytokines in the initiation and progression of the uveitis. Methods A series of 75 patients with acute uveitis,and 30 healthy persons from our hospital were investigated. The levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase and convalescent phase were measured by the enzymelinked immunosorbent assay. Result The serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase were significantly higher than that of the convalescent phase and the healthy controls (F=65.805/50.418/155.381, P=0.000). A significant negative correlation was found between the serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase with their initial visual acuity(r=-0.656, -0.592 and -0.653, Plt;0.01). There was also a positive correlation among the serum levels of INF-gamma;, TNF-alpha; and IL-6(r=0.340, 0.467 and 0.338, Plt;0.05). Conclusions There are high serum levels of INF-gamma;, TNF-alpha; and IL-6 in patients with acute uveitis, and the cytokines levels were decreased after the treatment. The results suggested that the INF-gamma;, TNF-alpha; and IL-6 involved in initiation and progression of uveitis.
【Abstract】Objective To investigate the potential role of tumor necrosis factoralpha (TNFα) in apoptosis after combined liver and kidney transplantation in rats. MethodsEighty rats which had combined liver and kidney transplantation were randomly paired, were divided into study group (n=20) and control group (n=20). 40 ml of 4 ℃ sodium chloride and antiTNFα monoclonal antibody (30 ml was infused from portal veins to donated livers and 10 ml from renal arteries to donated kidneys) were infused to the study group (0.1 mg/kg weight),and the same quantity of 4 ℃ sodium chloride was infused the control group. Venous blood was drew at different phases after the transplantations to detect the function of kidney and liver. The level of TNFα and the cell apoptosis were detected in the transplanted tissues of liver and kidney by ELISA and terminal deoxynucleotidy transferase mediated dTUPbiotin nickend labeling (TUNEL). ResultsThe levels of AST, ACT, Cr and BUN in the study group were significantly lower than those of the control group at the same phases (P＜0.05). The level of TNFα in the transplanted tissues of kidney and liver was also significantly lower as compared with those of control group. The cell apoptosis index of the transplanted tissues of kidney and liver was significantly smaller in the study group （P＜0.05）. There was no dramatically pathological change in the tissues of transplanted kidney and liver, which were treated with antiTNFα monoclonal antibody, and the structures are almost normal. ConclusionAntiTNFα monoclonal antibody may reduce cell apoptosis and accelerate the restoration of function of liver and kidney after combined liver and kidney transplantation.
ObjectiveTo dynamically observe the effect of N-acetylserotonin (NAS) on the expression of tumor necrosis factor-α (TNF-α) protein in retina of retinal ischemia reperfusion injury (RIRI) rats, and to explore the mechanism.MethodsBy using random number table method, 90 healthy male Sprague-Dawley rats were divided into sham operation group (n=10), RIRI group (n=40), and NAS group (n=40). The right eye was as the experimental eye. In the RIRI group and NAS group, the anterior chamber high intraocular pressure method was used to establish the RIRI model. In the NAS group, 10 mg/kg NAS was injected intraperitoneally before modeling and 30 minutes after modeling. At 6, 12, 24, 72 h after modeling, hematoxylin-eosin staining was used to observe the pathological changes of the retina, and the retinal ganglion cells (RGC) were counted. Each group was detected by immunohistochemical staining and Western blot about the relative expression of TNF-α, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein in the rat retina. One-way analysis of variance was used for differences between groups. The general linear regression method was used to analyze the correlation between the relative expression changes of TNF-α protein and the changes of Nrf2 and HO-1 protein expression after NAS intervention.ResultsOptical microscope observation revealed that the retinal edema of rats in the RIRI group was observed at 6, 12, and 24 h after modeling; the thickness of the retina in the NAS group was significantly thinner than that in the RIRI group, and the difference was statistically significant (F=9.645, 477.150, 2.432; P＜0.01). At 6, 12, 24, and 72 h after modeling, the retinal RGC counts in the NAS group were significantly higher than those in the RIRI group, and the difference was statistically significant (F=12.225, 12.848, 117.655, 306.394; P＜0.05). The results of immunohistochemical staining and Western blot showed that 6 h after modeling, the relative expression of TNF-α protein in the retina of the RIRI group increased significantly compared with that in the sham operation group, reaching a higher level at 12 h, and decreased at 24 and 72 h. But all were significantly higher than the sham operation group, the difference was statistically significant (immunohistochemical staining: F=105.893, 1 356.076, 434.026, 337.351; P＜0.01; Western blot: F=92.906, 534.948, 327.600, 385.324; P＜0.01). At different time points after modeling, the relative expression of TNF-α protein in the retina of the NAS group was significantly lower than that of the RIRI group (immunohistochemical staining: F=15.408, 570.482, 21.070, 13.767; P＜0.05; Western blot: F=12.618, 115.735, 13.176, 111.108; P＜0.05), but still higher than the sham operation group (immunohistochemical staining: F=40.709, 151.032, 156.321, 216.035; P＜0.01; Western blot: F=33.943, 79.729, 74.057, 64.488; P＜0.01), the difference was statistically significant; 12 h after modeling, Nrf2 in the retina of the NAS group (immunohistochemical staining: F=51.122, P＜0.05; Western blot: F=33.972, P＜0.05), HO-1 (immunohistochemical staining: F=30.750, P＜0.05; Western blot: F=18.283, P＜0.05) protein relative expression was significantly higher than that of RIRI group, and the differences were statistically significant. The results of linear regression analysis showed that the difference in the number of TNF-α+ cells in the RIRI group and the NAS group was negatively correlated with the difference in the number of Nrf2+ and HO-1+ cells (r2=0.923, 0.936; P＜0.01).ConclusionsNAS can inhibit the expression of TNF-α protein in the retina of RIRI rats and reduce RIRI. The mechanism may be related to the Nrf2/HO-1 pathway.
The exact pathophysiological mechanisms of retinopathy of prematurity (ROP) remain elusive. The risk factors of ROP include excessive oxygen therapy, malnutrition, infection and inflammation. Among the factors above, the effect of inflammation on ROP has received more attention. TNF-α is a biological active protein which is involved in neovascularization and inflammation. It may play a role in the development of ROP. This review summarized the studies on the association between TNF-α and ROP in recent years, so as to provide a new way to further study the pathogenesis and treatment methods of ROP.
ObjectiveTo investigate the mechanism of lung tissue apoptosis in LPS-induced mice ARDS via TNF-α neutralization. MethodsThirty-six mice were randomly divided into a control group,a LPS group,and TNF-α neutralization group.LPS(5 mg/kg) was intratracheally nebulized to induce ARDS in the LPS group and the TNF-α neutralization group.Twenty-four hours before LPS treatment,etanercept (0.4 mg/kg) was abdominal injected to the mice in the TNF-α neutralization group.Mice were sacrificed 2 hours after LPS treatment.PCR were used to detected the expression of NF-κB p65,Bax and Bcl-2 in lung tissue.Western blot were used to detected protein level of NF-κB p65,Erk1/2 and their phosphorylation and Bax,Bcl-2.The lung dry-to-wet ratio was measured.The lung histological changes were evaluated by HE staining. ResultsActivation level of NF-κB p65 and Erk1/2 was elevated,the ratio of Bcl-2 and Bax was decreased in the LPS group(P<0.05).After TNF-α neutralization,the activation level of NF-κB p65 and Erk1/2 were reduced,the ratio of Bcl-2 and Bax was increased (P<0.05).Compared with the LPS group,the lung dry-to-wet ratio and lung injury semi-quantitative score were significantly decreased in the TNF-α neutralization group (P<0.05). ConclusionTNF-α neutralization can suppress lung injury in LPS-induced ARDS mice by inhibiting activation of NF-κB p65 and Erk1/2,increasing the ratio of Bcl-2 and Bax ratio,and eventually reducing apoptosis.
Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis, typically as chronic anterior uveitis with insidious onset. Delayed and inadequate treatment may result in loss of patients' vision and even blindness. For refractory or severe uveitis related to juvenile idiopathic arthritis, systemic immunosuppressive agents should be used as early as possible. With the advantage of controlling ocular inflammation, avoiding ocular complications and reducing the use of traditional immunosuppressant drugs and glucocorticoid, tumor necrosis factor-α inhibitors have been new therapeutic options for uveitis associated with juvenile idiopathic arthritis, although methotrexate is known as the first-line approach. However, there are no internationally unified guidelines for clinical issues regarding the timing of application, reduction and withdrawal of tumor necrosis factor-α inhibitors, and no agreement on the application of tumor necrosis factor-α inhibitors in the management of ocular complications either. An in-depth understanding of the application status and progress of tumor necrosis factor alpha inhibitors in the treatment of juvenile idiopathic arthritis-associated uveitis has important clinical significance.