ObjectiveTo investigate the expression of tumor necrosis factor α(TNF-α ) in isolated rat heart at different time points after myocardial hypoxia/reoxygenation. MethodsThe isolated langendorff perfused rat heart model was established. Forty-eight SD rats were randomly divided into four groups: a sham group, hypoxia/reoxygenation groups including a H/R 0.5 h group, a 1 h group and a 2 h group. The heart rate(HR), the 1eft ventricular development pressure(LVDP), maximal rates of increase/decrease of the left ventricular pressure(±dp/dtmax) were continuously recorded. The concentrations of TNF-α and creatine kinase-MB(CK-MB) in myocardium, mRNA expression of TNF-α in myocardium were tested. Ultra structure of myocardium was observed under electron microscope. ResultsThe levels of LVDP, ±dp/dtmax, and HR of hypoxia/reoxygenation group were significantly lower than those in the sham group(P<0.05).The levels of TNF-α and CK-MB and the expressions of TNF-α at mRNA level in the hypoxia/reoxygenation group were higher than those in the sham group(P<0.05).There were significant differences in the above parameters among the H/R 0.5 h group, the 1 h group, the 2 h group(P<0.05).The concentrations of TNF-α and CK-MB, the mRNA expression of TNF-α were higher in the I/R 2 h group than those in the other two groups. ConclusionThe high expression of TNF-α in myocardium after myocardial hypoxia/reoxygenation in rats is related to the degree of myocardium damage and may lead to myocardial injury.
ObjectiveTo investigate the association between TNF-α gene -308G/A polymorphism and the risk of coronary atherosclerotic heart disease (CHD) in Chinese population.MethodsWe searched PubMed, Web of Science, CNKI, WanFang Data and VIP Databases from inception to February 2017, to collect case-control studies about the association between TNF-α gene -308G/A polymorphism and risk of CHD in Chinese population. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was performed by Stata 12.0 software.ResultsA total of 10 case-control studies were included. The results of meta-analysis showed a significant association between the TNF-α gene -308G/A polymorphism and CHD risk in Chinese population (A vs. G: OR=1.13, 95%CI 1.02 to 1.26, P=0.020; AA vs. GA/GG: OR=1.47, 95%CI 1.02 to 2.12, P=0.038; AA vs. GG: OR=1.50, 95%CI 1.04 to 2.16, P=0.029).ConclusionThe current evidence shows that the TNF-α gene -308G/A polymorphism may be associated with CHD risk in Chinese population and A allele may be a risk factor. Due to the limited quantity and quality of included studies, more high quality studies are needed to verify the above conclusion.
Objective To summarize results of the correlation of tumor necrosis factor-α (TNF-α) promoter –308A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility in Chinese populations. Methods We collected all the publications about the correlation between TNF-α promoter –308A/G polymorphism and SLE in Chinese populations by searching PubMed, EBSCO, CBM, CNKI and Wanfang Data before the date of March 20, 2010. Meta-analysis was performed for checking the difference between two groups about genotypes such as AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele. Results A total of 8 studies involving 731 SLE patients and 901 healthy people were included. The meta-analysis of total populations showed that, there was no significant correlation between A allele and increased SLE risk (OR=1.42, 95%CI 0.97 to 2.09, P=0.07); the meta-analyses of populations in different regions showed there was no significant correlation of A allele and increased SLE risk in Chinese Taiwan populations (OR=1.04, 95%CI 0.77 to 1.40, P=0.82). Moreover, there was no significant difference between SLE group and control group in the genotypes of AA versus GG, GA versus GG, AA versus GG+GA, and GA+AA versus GG.Conclusion This meta-analysis dosen’t demonstrate the correlation between TNF-α promoter–308A/G polymorphism and SLE in Chinese populations.
Objective To observe the human mononuclear cell releasing TNF-α and the activation of Caspase-3 during apoptosis after stimulated by Co2+ and Cr3+, to discuss the mechanism of artificial joint wear production metal ion on aseptic loosening. Methods CoCl2 powder and CrCl3 powder were dissolved by asepsis inject water, preparing solution for10 mg/L and 500 mg/L, respectively. Mononuclear cells were acquired from peripheral blood, 4 × 106/culture dish. According to the difference of culture solution, the cells were divided into 3 groups. Group A: mononuclear cell was culture with normal sal ine as control; group B: mononuclear cell was cultured with CoCl2 solution; group C: mononuclear cell was cultured with CrCl3 solution. The production of TNF-α was assessed by ELISA, the activation of Caspase-3 was measured by colorimetric assay and the apoptotic cell was detected by TUNEL assays at 12, 24 and 48 hours after co-cultured respectively. Results The concentration of TNF-α and the expression of Caspase-3 in groups B and C were higher than those in group A (P lt; 0.05), and reached the peak level at 24, 48 hours, respetively. The TUNEL positive cells were detected in the all groups, nucleus was pyknotic and darker-staining, cell body was crinkle and cell membrane was integrity. There were significant differences in the apoptosis rate between groups B, C and group A (P lt; 0.05). And the activation of Caspase-3 increased and had the positive correlation with the apoptosis rate (r=0.765). Conclusion Co2+ and Cr3+ ions can stimulate human mononuclear cell to release TNF-α and induce human mononuclear cell apoptosis, which result in periprosethetic osteolysis and related to activation of Caspase-3.
Objective To investigate the effect of heme oxygenase 1 (HO-1) on the apoptosis of human degenerated nucleus pulposus (NP) cells induced by tumor necrosis factor α (TNF-α), and explore its possible molecular mechanism. Methods The intervertebral disc tissues were derived from patients with lumbar intervertebral disc herniation. Then, the NP cells were cultured in vitro and the third generation of NP cells were used for subsequent experiments. Cell counting kit 8 (CCK-8) method was used to observe the proliferative effect of TNF-α on the NP cells in vitro at the concentration of 10, 20, 50, 100, and 200 ng/mL. The most apropriate concentration was selected according to the result of CCK-8. The NP cells were cultured with basal medium (control group), TNF-α (TNF-α group), TNF-α and CoPP 10 μmol/L (CoPP group), and TNF-α and ZnPP 15 μmol/L (ZnPP group), respectively. After cultured, the cell poptosis was detected by Hoechst staining and flow cytometry; the expression of cleaved Caspase-3, epithelial membrane protein 1 (EMP-1), HO-1, and p-P65 proteins were detected by Western blot. In order to further explore the potential molecular mechanisms of HO-1 for cell apoptosis, the NP cells were cultured with TNF-α (TNF-α stimulated group), TNF-α and pyrrolidine dithiocarbamate (PDTC) 5 μmol/L (TNF-α+PDTC stimulated group), respectively. Then the cell apoptosis rate was measured by flow cytometry at 24 hours after cultured. Results The optimal concentration of TNF-α was 100 ng/mL. Hoechst staining showed that a few apoptotic cells could be observed in control group and CoPP group; the apoptosis-like nucleis were observed in TNF-α group and ZnPP group, which was the most significant in ZnPP group. Flow cytometry showed that the cell apoptosis rates of TNF-α group, CoPP group, and ZnPP group were significantly increased when compared with the control group (P<0.05). Compared with TNF-α group, the cell apoptosis rate in CoPP group decreased (P<0.05), while in ZnPP group it increased (P<0.05). Western blot showed that the expression of HO-1 protein in TNF-α group was decreased, and the expressions of cleaved Caspase-3, EMP-1, and p-P65 proteins were increased when compared with the control group (P<0.05). Compared with TNF-α group, the expression of HO-1 protein in CoPP group increased, and the expressions of cleaved Caspase-3, EMP-1, and p-P65 proteins were reduced (P<0.05); the expression of HO-1 protein in ZnPP group decreased (P<0.05), the expressions of cleaved Caspase-3 and EMP-1 proteins increased (P<0.05), and the expression of p-P65 protein was not significantly changed (P>0.05). Compared with TNF-α stimulated group, the cell apoptosis rate in TNF-α+PDTC stimulated group was significantly reduced (t=3.076, P=0.031). Conclusion HO-1 can inhibit the apoptosis of degerated NP cells induced by TNF-α, and its mechanism effect is by inhibiting the nuclear factor кB signaling pathway.
急性肺損傷(acute lung injury,ALI)是臨床常見的呼吸系統急危重癥,其發病機制復雜,病死率高。腫瘤壞死因子α(tumor necrosis factor-α,TNF-α)是ALI發生、發展過程中非常重要的細胞因子。本文就TNF-α在ALI中的作用和以抗TNF-α為靶點治療ALI的相關研究進行綜述。
ObjectiveTo investigate the effect of the femoral tunnel angle on the femoral tunnel after anterior cruciate ligament (ACL) reconstruction in rabbits. MethodsFifty-four healthy 4-5 months old rabbits (weighing, 1.8-2.3 kg, male or female) were randomly divided into 3 groups (n=18). The ACL reconstruction models of the right knee were established in 3 experimental groups using its Achilles tendons, and the left knee served as the control group. On the coronal position, the angle between the femoral tunnel and the femoral shaft axis was 30°, 45°, and 60°. The level of tumor necrosis factor α (TNF-α) in the synovial fluid at 1, 2, and 4 weeks, the maximum load of the ligament and the rate of bone tunnel enlargement at 4, 8, and 12 weeks were detected. ResultsThe level of TNF-α significantly increased, and the maximum load of the ligament significantly decreased in the 3 experimental groups when compared with ones in the control group (P<0.05), but no significant difference was found among 3 experimental groups (P>0.05). The bone tunnel enlargement was observed in 3 experimental groups at each time point and reached the peak at 4 weeks, but no significant difference was shown among 3 groups (P>0.05). ConclusionThe 30-60° angle between the femoral tunnel and the femoral shaft axis in the coronal position has no significant effect on the femoral tunnel enlargement after ACL reconstruction in rabbits.
Objective To comprehensively evaluate the association between TNF-α gene ?308 G/A polymorphism and the risk of prostate cancer. Methods A meta-analysis was performed to analyze the association between ?308 G/A polymorphism and the risk of prostate cancer risk. Results A total of 11 case-control studies (4 919 cases and 5 210 controls) were included in this meta-analysis. The result showed no statistically significant differences in all genotype distribution between prostate cancer cases and controls: dominant model (OR=1.11, 95%CI 0.90 to 1.36, P=0.33), recessive model (OR=0.91, 95%CI 0.70 to 1.18, P=0.47), GA versus GG (OR=1.11, 95%CI 0.90 to 1.37, P=0.33), AA versus GG (OR=0.92, 95%CI 0.71 to 1.20, P=0.55), A versus G (OR=1.07, 95%CI 0.91 to 1.26, P=0.39). In the subgroup analysis by ethnicity, no statistically differences were found between prostate cancer cases and controls. Conclusion This results of meta-analysis suggests that TNF-α gene –308G/A polymorphism may not be a risk factor of prostate cancer. Due to the limited quantity of the includied studies, further studies are needed to validate the above conclusion.
ObjectiveTo investigate the role of Wnt5a in the mechanism of radiculopathy and the relation between Wnt5a and tumor necrosis factorα(TNF-α) by observing the change of the expression of Wnt5a in the rat model of chronic compression of dorsal root ganglia (CCD). MethodsA total of 192 adult male Sprague Dawley rats were allocated into 4 groups: shame group (group A, n=48), CCD group (group B, n=48), CCD+sal ine group (group C, n=48), and CCD+etanercept group (group D, n=48). An L-shaped needle (about 3.5 mm in length, 0.6 mm in diameter) was inserted into the L5 intervertebral foramen, and the dorsal root ganglia (DRG) was compressed by the needle to prepare the CCD model in groups B, C, and D, and then normal sal ine (5.5 mg/kg) or etanercept was injected intraperitoneally in groups C and D. The intervertebral foramen was exposed in group A. The mechanical pain threshold of the posterior paw was tested by the von Frey filaments at 1, 3, 5, and 7 days after operation; the expressions of Wnt5a protein and mRNA were detected at 3 and 7 days after operation by immunohistochemical staining and RT-PCR, respectively. ResultsThe mechanical pain threshold of groups B and C was significantly lower than that of groups A and D, and in group D than in group A (P < 0.05), but no significant difference was found between groups B and C (P > 0.05). The Wnt5a positive cells and the mRNA expression of Wnt5a at 7 days were significantly more than those at 3 days in groups B, C, and D (P < 0.05). The Wnt5a positive cells and the mRNA expression of Wnt5a in groups B and C were significantly more than in groups A and D, and in group D than in group A (P < 0.05), but no significant difference was shown between groups B and C (P > 0.05). ConclusionThe expression of Wnt5a in the DRG is increased after CCD. The expression of Wnt5a in the DRG is decreased after the administration of the inhibitor of TNF-α.
Objective To discuss the relationship between the changes of hepatic blood flow detected by usingspectral Doppler ultrasound and serum TNF- α and IL-1 β levels after liver ischemia/reperfusion （I/R） of rat. Methods The hepatic ischemia 15 min and reperfusion models were established by using pringle method. The hepatic blood flow of hepatic artery and portal vein at 1， 6， and 24 hours after liver I/R were detected by using spectral Doppler ultrasound， the total blood flow volume （FV） was calculated， and the serum TNF- α and IL-1 β levels at each time point were detected. The correlation between the TNF-α， IL-1 β， and FV were analyzed. Results The FV at 1 hour and 6 hours after reperfusion in I/R group were less than those in sham operation （SO） group 〔（52.08±11.88） mL/min vs. （85.32±29.85） mL/min and （44.69±8.75）mL/min vs. （81.41±28.67） mL/min， P＜0.05〕. The FV at 24 hours after operation or reperfusion of 2 groups was no significant differences （P＞0.05）. The serum content of TNF-α at 1 hour after reperfusion in I/R group was higher than that in SO group 〔（310.52±39.83）pg/mL vs. （240.74±31.65）pg/mL， P＜0.05〕. The serum contents of TNF-α at 6 and 24 hours after operation or reperfusion of 2 groups were no significant differences （P＞0.05）. The serum contents of IL-1β at 1 hour and 6 hours in I/R group were higher than those in SO group 〔（38.08±3.73） pg/mLvs. （22.03±0.79） pg/mL and （27.44±6.11） pg/mL vs. （21.78±0.71） pg/mL， P＜0.05〕. The serum content of IL-1β at 24 hours after operation or reperfusion of 2 groups was no significant differences （P＞0.05）. There was a negative correlation between the FV and TNF-α or IL-1β （r=-0.43， P＜0.05；r=-0.46， P＜0.05）. Conclusions Spectral Doppler ultrasound can observe the changes of hepatic blood flow and evaluate the hepatic microcirculation indirectly. The hepatic blood flow after liver I/R decreases and it may be related to over expression of TNF-α and IL-1β.