ABSTRACT
Objective:To explore the effect of 1-methyltryptophan (1-MT) on lipopolysaccharide (LPS)-induced permeability and apoptosis of human umbilical vein endothelial cells (HUVECs).Methods:HUVECs were treated with phosphate buffer saline (PBS, control group), 1 μg/mL LPS (LPS group), and LPS combined with 1 mmol/L 1-MT (1-MT group). The expression levels of the p120 concatemer (p120ctn), vascular endothelial (VE) cadherin, caspase-3, and DNA repair enzyme polyadenylate ribose polymerase-1 (PARP) after incubation at 8 h were detected using Western blot. The concentrations of kynurenine (Kyn) after incubation at 2, 4, 6, and 8 h were measured by high-performance liquid chromatography, and indoleamine2, 3-dioxygenase (IDO) activity was calculated. Comparisons among groups were performed using the LSD- t test. Results:Compared with the control group, the expression of caspase-3 [(74.01±7.91)% vs (157.14±7.63)%, P<0.01] and the concentration of Kyn were significantly up-regulated, while the expression of p120ctn [(49.12±2.15)% vs (37.61±1.80)%, P<0.01], VE-cadherin [(107.70±7.01)% vs (90.66±2.58)%, P=0.027], and PARP-1 [(67.95± 3.08)% vs (57.93±5.26)%, P=0.038] were significantly down-regulated, and IDO activity was significantly increased in the LPS group ( P<0.05). Compared with the LPS group, the expression of caspase-3 [(157.14±7.63)% vs (110.74±7.89)%, P<0.01] was significantly down-regulated, while the expression of p120ctn [(37.61±1.80)% vs (47.19±0.82)%, P<0.01], VE-cadherin [(90.66±2.58)% vs (107.27±9.89)%, P=0.029], and PARP-1 [(57.93±5.26)% vs (74.12±4.90)%, P=0.005] were significantly up-regulated, and the activity of IDO was significantly decreased over time in the 1-MT group ( P<0.05). No significant differences were observed between the PBS and 1-MT groups in the protein levels of p120ctn, VE-cadherin, and PARP-1 protein as well as Kyn concentration and IDO activity ( P>0.05), while the expression of caspase-3 was increased in 1-MT group ( P=0.001). Conclusions:LPS aggravates the permeability of HUVECs, which can be reversed by 1-MT via inhibiting IDO activity and reducing Kyn concentrations. Moreover, 1-MT can also reduce apoptosis, which may be via increasing the expression of PARP-1 and reducing the expression of caspase-3, thus protecting endothelial cells.
ABSTRACT
Objective To investigate the application of the cross-sectional area ratio of internal jugular vein and common carotid artery (IJV/CCA) in the evaluating the volume responsiveness of critically ill patients. Methods The capacity of critically ill patients were prospectively assessed. The diameter and sectional area of the IJV and CCA were measured by bedside ultrasonography. The cross-sectional area ratio of IJV/CCA was calculated and compared with the variety of cardiac output (ΔCO) after passive leg raising (PLR). Then the correlation index between the cross-sectional area ratio of IJV/CCA and ΔCO was evaluated, and the sensitivity and specificity parameters of capacity status were assessed by the cross-sectional area ratio of IJV/CCA. Results Of 55 critically ill patients in this study, 34 cases had positive volume responsiveness, and 21 case negative volume responsiveness.The general clinical data of the two groups had no statistically significant difference. The cross-sectional area ratio of IJV/CCA in the positive group was significantly less than that of the negative group (1.38±0.55 vs. 2.16±0.68, P<0.01). There was a significant correlation between the IJV/CCA cross-sectional area ratio and the ΔCO value of PLR (r=-0.67, P<0.01). When the ratio of the cross-sectional area of IJV/CCA was 1.65, the sensitivity of the assessment capacity was 86.4％ and the specificity was 78.8％. Conclusions The use of portable bedside ultrasonography is a noninvasive, convenient and reliable method to evaluate the capacity state of the critically ill patients.