1.
The protective effects of L-carnitine on myocardial ischaemia-reperfusion injury in patients with rheumatic valvular heart disease undergoing CPB surgery are associated with the suppression of NF-κB pathway and the activation of Nrf2 pathway.
Li, M, Xu, S, Geng, Y, Sun, L, Wang, R, Yan, Y, Wang, H, Li, Y, Yi, Q, Zhang, Y, et al
Clinical and experimental pharmacology & physiology. 2019;(11):1001-1012
Abstract
Myocardial ischaemia-reperfusion injury (MIRI) is a main pathophysiologic change following CPB surgery. L-carnitine, a natural amino acid, is able to transport fatty acids for generating energy and has a protective effect on MIRI. We aim to investigate the protective effect of L-carnitine on MIRI in patients with rheumatic valvular heart disease (RVHD) performed CPB surgical operation and the underlying mechanism. In this study, patients were randomized to three groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (6 g/L) and experimental group 2 (12 g/L), whereas no L-carnitine was used in the control group. Our results showed that L-carnitine significantly attenuated myocardial injury after surgery in these patients. L-carnitine decreased serum markers of myocardial injury including CK-MB, cTnI, hs-cTnT and IMA. L-carnitine increased left ventricular ejection fraction (LVEF) but reduced wall motion score index (WMSI) after operation. L-carnitine also inhibited myeloperoxidase (MPO) activity and inflammatory cytokines in the myocardium of patients after unclamping the aorta. Additionally, L-carnitine increased levels of superoxide dismutase (SOD) and catalase (CAT) while decreased levels of malondialdehyde (MDA) and protein carbonyl content in the myocardium of patients after unclamping the aorta. Moreover, L-carnitine suppressed the activation of nuclear factor kappa B (NF-κB) and activated nuclear factor erythroid 2-related factor 2 (Nrf2). There was also no significant difference in these indices between two experimental groups after unclamping the aorta. Taken together, L-carnitine had a protective effect against CPB-induced MIRI in patients with RVHD, which might be related to its modulation of NF-κB and Nrf2 activities.
2.
NF-κB activation and cell death after intracerebral hemorrhage in patients.
Zhang, Z, Liu, Y, Huang, Q, Su, Y, Zhang, Y, Wang, G, Li, F
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2014;(7):1097-102
Abstract
Nuclear factor-κB (NF-κB) plays an important role in secondary damage after intracerebral hemorrhage (ICH). We explored NF-κB activation and the relationship between NF-κB and cell death in the perihematomal brain tissue of patients after ICH. According to the interval between onset of hemorrhage and specimen collection, 53 cases of patients with basal ganglia hemorrhage were divided into six experimental groups: 0-6, 7-12, 13-24, 25-48, 49-96, and >96 h group. Brain tissues of the experimental groups and control group were collected. IL-1β, TNF-α, and NF-κB p65 expressions at the protein level were detected by immunohistochemistry. Cell death was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. All of the detection items of immunohistochemistry and TUNEL showed significant differences between the experimental groups and control group. At the protein level, nuclear NF-κB p65, IL-1β, and TNF-α achieved maximum values at 13-48, 0-24, and 13-48 h, respectively. Maximum cell death was reached at 13-48 h. NF-κB activation increased dramatically in perihematomal brain tissue after ICH. NF-κB activation was closely related with cell death and had an important function in secondary brain damage after ICH in patients.
3.
[The DNA binding activity of nuclear factor-ΚB in patients with severe pneumonia and the intervention effects of Xuebijing injection].
Gong, BL, Zhang, Y, Xu, QX, Chen, YQ
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue. 2010;(9):543-6
Abstract
OBJECTIVE To investigate the role of nuclear factor-ΚB (NF-ΚB) in severe pneumonia and observe the effects of Xuebijing injection in its treatment. METHODS Thirty hospitalized patients with severe pneumonia were divided into the routine therapy group (n=14) and Xuebijing therapy group (n=16) in whom with Xuebijing injection 100 ml was given once daily for 7 days besides routine therapies, according to the random numeral. The DNA binding activity of NF-ΚB in human monocytes was detected before and 3 days and 7 days after administration, the contents of tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were determined, and the changes in coagulatory and fibrinolytic parameters were assayed at the same time. Acute physiology and chronic health evaluationII (APACHEII) score was also recorded. Ten healthy volunteers served as the healthy control group. RESULTS The DNA binding activities of NF-ΚB, the contents of TNF-α, PCT, CRP, fibrinogen (Fib), D-dimer in hospitalized subjects with severe pneumonia were higher before treatment than those in healthy control group, while the prothrombin time (PT), thrombin time (TT) were significantly lower (P<0.05 or P<0.01). Compared with the routine therapy group, the DNA binding activity of NF-ΚB (grey level) at the 7 days (66.60±36.23 vs. 79.90±39.11) was notably decreased in Xuebijing therapy group; the levels of TNF-α (ng/L, 25.81±11.67 vs. 33.78±13.36), PCT (μg/L, 1.91±1.09 vs. 2.96±1.80), CRP (mg/L, 20.01±7.21 vs. 26.59±10.66), Fib (g/L, 4.02±1.26 vs. 5.09±1.43), D-dimer (mg/L, 0.24±0.06 vs. 0.31±0.11) were significantly lower in Xuebijing therapy group, and APACHEII score (15.81±3.47 vs. 17.93±3.05) was obviously lowered (all P<0.05). There was statistical difference of the TT (s) between two groups at 3 days (15.68±1.89 vs. 14.65±1.33,P<0.05). There was a significant positive correlation between NF-ΚB DNA binding activity and the levels of TNF-α (r(1)=0.373, r(2)=0.362, r(3)=0.419), PCT (r (1)=0.800, r(2)=0.716, r(3)=0.920) or CRP (r(1)=0.368, r(2)=0.441, r(3)=0.366, all P<0.05) before and 3 days and 7 days after the treatment. CONCLUSION NF-ΚB activation and coagulopathy were observed in patients with severe pneumonia, and NF-ΚB was involved in the process of inflammatory response. Inflammatory response was partly alleviated by Xuebijing injection. These effects of Xuebijing injection may be mediated by inhibition of the activation of NF-ΚB and its anticoagulation property.