RESUMEN
Objective:To observe whether endoplasmic reticulum stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation were involved in severe heat stroke induced intestinal mucosal injury and to investigate the potential protective effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA).Methods:Thirty male BALB/c mice were randomly (random number) assigned to 3 groups: the control group, heat stroke group (HS), and 4-PBA pretreatment group (4-PBA+HS, 4-PBA 120 mg/kg, intraperitoneal injection). Mice in the control group were placed at room temperature, while mice in the HS group and 4-PBA+HS group were placed in a prewarmed chamber [temperature (35.5±0.5) °C, humidity (60.0±5.0)%]. A rectal temperature (Tc) that reached 42 °C was considered to indicate severe heat stroke. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) in intestinal homogenate were analyzed by a colorimetric method, serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) were assessed by ELISA, intestinal histopathology was evaluated by hematoxylin and eosin (HE) staining, intestinal ultrastructure was observed by electron microscopy, and the protein expression of GRP78, CHOP, NLRP3 and cleaved caspase-1 were analyzed by Western blot. Data were statistically analyzed by ANOVA test and LSD- t multiple comparison test if homogeneous variance, or analyzed by Welch test and Dunnett's T3 multiple comparison test if heterogeneous variance. Results:The concentration of MDA in the HS group was increased ( t=14.243, P<0.01), while SOD was decreased compared with that in the control group ( t=7.781, P<0.01), and the concentrations of serum IL-1β and IL-18 were significantly elevated ( t=12.664, P<0.01; t=16.240, P<0.01). Under light microscopy, extensive destruction of small intestinal villi and inflammatory cell infiltration were observed in the intestines of mice with severe heat stroke. Transmission electron microscopy showed that endoplasmic reticulum structures were significantly expanded, and mitochondria were vacuolated in the intestines of mice with severe heat stroke. Compared with those in the control group, the protein expression levels of GRP78, CHOP, NLRP3 and cleaved caspase-1 in the small intestine were elevated in the HS group ( t=14.824, P <0.01; t=12.667, P<0.01; t=9.298, P<0.01; and t=6.588, P=0.001). Compared with those in the HS group, mice in the 4-PBA pretreatment group exhibited reduced concentrations of MDA ( t=9.167, P<0.01), increased SOD ( t=6.077, P<0.01) , and reduced serum IL-1β and IL-18 levels ( t=4.889, P= 0.001; t=5.693, P<0.01). In addition, 4-PBA pretreatment significantly alleviated the pathological disruption and ultrastructural damage to small intestine tissues. Moreover, 4-PBA pretreatment reduced GRP78, CHOP , NLRP3 and cleaved caspase-1 protein expression ( t=9.080, P<0.01; t=7.152, P<0.01; t=4.249, P=0.005; t=3.650, P=0.011). Conclusions:Endoplasmic reticulum stress and NLRP3 inflammasome are involved in intestinal mucosal injury induced by severe heat stroke. 4-PBA plays a protective role by alleviating endoplasmic reticulum stress and NLRP3 inflammasome activation.
RESUMEN
Objective:To investigate the effect of ethyl pyruvate on proliferation activity of vascular endothelial cells after heat stress.Methods:Human umbilical vein endothelial cells (HUVECs) were placed in incubators with different temperatures (39 ℃, 41 ℃, 43 ℃) for heat shock for 4 h, or placed into the incubator with the same temperature at 43 ℃ and received heat shock for different times (2 h, 3 h, 4 h), and the control group were always placed in 37 ℃ incubator. Then the morphological changes of the cells were observed under an inverted microscope, and the cell proliferation activity was detected by the cell counting - 8 (CCK-8) kit. According to the above experimental results, the optimal intervention temperature (43 ℃) and time point (4 h) of heat stress were selected. After that, ethyl pyruvate (EP) with a concentration of 10 μmol/L was used for intervention (HS+EP group), and the cell proliferation activity was detected by CCK-8.Results:With the increasing of the heat stress temperature or the extension of exposure time, the cell morphology gradually changed under the inverted microscope, and the cells in 43 ℃ incubator for 4 h was the most obvious; and the cell proliferation activity of HUVECs decreased gradually, and the most significant decrease occurred in the group that exposure for 4 h in 43 ℃ ( F=25.79, P < 0.001 vs. control group). In addition, the cell proliferation activity of HUVECs in the HS+EP group was significantly higher than that in the HS group ( P < 0.001). Conclusions:EP can reduce significantly the effect of heat stress on the proliferation activity of HUVECs, and help to alleviate the changes of vascular endothelial cell activity caused by heat stress.
RESUMEN
Diaphragm dysfunction is common in clinical work, which is a frequently important cause of ventilation weaning failure ignored by clinicians. Assessing diaphragmatic function while weaning helps early detection and prevention of weaning failure, so as to improve the clinical outcome of patients on mechanical ventilation (MV). Reviewing studies of diaphragmatic function evaluation in weaning, we can find that assessing diaphragmatic function during weaning can help guide weaning. Weaning predictors including pressure index, electrophysiological index and morphological index, among which bedside ultrasound as a morphological index is widely used in intensive care unit (ICU), which is simple, non-invasive, and easy to operate. It is also accurate in the assessment of diaphragmatic function and guidance on weaning, which is worthy of promotion and application.