Objective To study the effect and mechanism of Xuebijing injection on sepsis-induced acute lung injury (ALI) in mice by regulating autophagy. Methods A total of 80 BALB/c male mice were randomly divided into control group, model group, Xuebijing group and Xuebijing+3-methyladenosine (3-MA) group, with 20 mice in each group. The control group received sham operation, while sepsis-induced ALI model was established in the later three groups by cecal ligation and puncture, on that basis, the Xuebijing group was given 10 mL/kg Xuebijing by intraperitoneal injection and the Xuebijing+3-MA group was given 10 mL/kg Xuebijing and 10 mg/kg autophagy inhibitor 3-mA by intraperitoneal injection. The cumulative survival rates of the four groups were observed 72 h after modeling, and the pathological changes of lung tissues, lung wet weight /dry weight ratios, inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1 β, and IL-18] contents, numbers of autophagosome, and the protein expression levels of autophagy genes [microtubule-associated protein light chain3 (LC3)-Ⅱ/LC3-Ⅰand Beclin-1] were detected. Results In the control group, the 72-hour cumulative survival rate was 100%, the lung wet weight /dry weight ratio was 3.89±0.85, the TNF-α, IL-1β, and IL-18 contents were (0.83±0.14) ng/mg, (0.74±0.15) ng/mg, and (84.51±13.25) pg/mg, respectively, the number of autophagosome was (0.41±0.09)/field, and the expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 were 0.20±0.04 and 0.17±0.03, respectively. In the model group, the lung tissue showed typical ALI pathological changes, the 72-hour cumulative survival rate (50%) was lower than that in the control group, and the lung wet weight /dry weight ratio (6.77±0.94), contents of TNF-α, IL-1β, and IL-18 [(3.15±0.76) ng/mg, (2.88±0.62) ng/mg, (274.62±45.58) pg/mg], autophagosome number [(3.14±0.55)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.69±0.09, 0.35±0.06) were higher than those in the control group (P<0.05). In the Xuebijing group, the ALI pathological changes alleviated, the 72-hour cumulative survival rate (75%), autophagosome number [(5.77±0.75)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.98±0.13, 0.62±0.08) were higher than those in the model group (P<0.05), and the lung wet weight /dry weight ratio (4.23±0.76) and contents of TNF-α, IL-1β, and IL-18 [(1.52±0.32) ng/mg, (1.29±0.30) ng/mg, (121.36±26.51) pg/mg] were lower than those in the model group (P<0.05). In the Xuebijing+3MA group, the ALI pathological changes aggravated, the 72-hour cumulative survival rate (55%), autophagosome number [(0.78±0.16)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.37±0.05, 0.32±0.05) were lower than those in the Xuebijing group (P<0.05), and the lung wet weight /dry weight ratio (6.31±0.91) and contents of TNF-α, IL-1β, and IL-18 [(2.88±0.56) ng/mg, (2.41±0.58) ng/mg, (252.35±37.65) pg/mg] were higher than those in the Xuebijing group (P<0.05). Conclusion Xuebijing injection can reduce ALI induced by sepsis in mice, and activation of autophagy is the molecular mechanism.
ObjectiveTo investigate the potential role and mechanism of hydrogen sulfide (H2S) in regulating arterial baroreflex (ABR) in septic rats. MethodsThe rat model of cecal ligation and puncture (CLP) induced sepsis was established. Fortyseven male SpargueDawley rats were randomly divided into 9 groups: ① Sham operation (SO)+0.9% NaCl (NS) intravenous injection (i.v.) group; ② SO+NaHS i.v. group; ③ CLP+NaHS i.v. group; ④ SO+artificial cerebrospinal fluid (aCSF) bilater nucleus tractus solitarii (NTS) microinjection group; ⑤ SO+NaHS bilater NTS microinjection group; ⑥ SO+vehicle (DMSO)+NaHS group; ⑦ SO+Gli+NaHS group; ⑧ CLP+vehicle (DMSO) group; ⑨ CLP+Gli group. The ABR function was measured before administration and 5 min and 30 min after administration. Results① The ABR value of rats at different time in the same group: Compared with the ABR value before administration in the SO+NaHS i.v. group, CLP+NaHS i.v. group, SO+NaHS bilater NTS microinjection group, and SO+vehicle+NaHS group, the ABR values of rats significantly decreased at 5 min and 30 min after administration (Plt;0.05, Plt;0.01), which significantly increased in the CLP+Gli group at 5 min and 30 min after administration (Plt;0.05). ② The ABR value of rats at the same time in the different groups: Before administration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v.group (Plt;0.05). At 5 min and 30 min after adminis tration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v. group (Plt;0.05), which in the SO+NaHS i.v. group or SO+NaHS bilater NTS microinjection group was significantly lower than that in the SO+NS i.v. group or SO+aCSF bilater NTS microinjection group, respectively (Plt;0.05, Plt;0.01), in the SO+Gli+NaHS group or CLP+Gli group was significantly higher than that in the SO+vehicle+NaHS group or CLP+vehicle group, respectively (Plt;0.05). ConclusionsH2S plays an adverse role in septic ABR function, and opening KATP channel located at the pathway of ABR, may be the mechanism involved in the downregulation of ABR function in septic rat. Notably, the NTS may be also responsible for reduction of ABR value.
ObjectiveTo explore the relationship between mitochondrial function and the severity of sepsis by detecting the platelet mitochondrial permeability transition pore, transmembrane potential and adenosine triphosphate (ATP) levels in peripheral blood. MethodsAccording to random number table, 40 male SD rats were randomly divided into three sepsis model groups (group A, B and C) and a sham group (group D). The rats in the model groups received cecal ligation and puncture (CLP) treatment with different percent of ligated length in total length of the cecum (10% in group A, 30% in group B and 50% in group C, respectively). Twenty-four hours later, peripheral blood was collected for TNF-α, IL-1βand IL-6 levels determination, also the mitochondrial permeability transition pore, transmembrane potential and ATP content were tested in the isolated platelet. One-way ANOVA test was used to determine the relevance between above indices and the severity of sepsis. Meanwhile, 29 patients with sepsis were enrolled for clinical study. After APACHEⅡscoring, platelet samples of peripheral blood in the patients were collected for mitochondrial function determination. The relationship between mitonchondrial function and APACHEⅡscore was analyzed by Spearman method. ResultsCalcein fluorescence, membrane potential and ATP synthesis in platelet mitochondria of the rat sepsis model were gradually decreased with the increased severity of CLP, and the difference among these groups were all statistically significant (all P < 0.05). In clinical specimens, APACHEⅡscore was negatively correlated with ATP level of platelet mitochondria(r=-0.895, P < 0.05). ConclusionMitochondrial function of platelet in peripheral blood can be used as an effective indicator for the severity of sepsis.
Objective To observe the effects of δ-opioid receptor agonists D-Ala2-D-Leu5-enkephali （DADLE） on hepatocyte apoptosis and expressions of bcl-2 and caspase-3 in septic rat, and to investigate the possible mechanism by which DADLE protects the liver in sepsis. Methods Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-four SD rats (either male or female) were randomly divided into CLP group (n=18), DADLE group (n=18) and sham operation (SO) group (n=18). The rats were respectively killed at different time (2 h, 4 h and 6 h after operation). Hepatocyte apoptosis was detected by TdT-mediated dUTP Nick End Labeling (TUNEL). The expressions of bcl-2 and caspase-3 protein were detected by immunohistochemistry. And the changes of pathology in hepatic tissue were detected by light microscope. Results The hepatic pathological lesion of rats in CLP group was obviously serious compared with SO group, while it was obviously improved in DADLE group. The apoptosis index of rat hepatocytes in CLP group significantly increased compared with SO group, and further it was prominent at 4 h （P＜0.01). The apoptosis index of rat hepatocytes at each time of DADLE group was significantly decreased compared with CLP group （P＜0.01）. Expression of caspase-3 protein in liver tissues of CLP group significantly increased compared with SO group （P＜0.01）, while the expression of bcl-2 protein significantly decreased （P＜0.05）. Expression of caspase-3 protein in liver tissues of DADLE group significantly decreased compared with the CLP group （P＜0.01）, while the expression of bcl-2 protein significantly increased （P＜0.05）. There was positive correlation between expression of caspase-3 in liver tissues and apoptosis index of hepatocyte (r=0.83, P＜0.01) and negative correlation between expression of bcl-2 in liver tissues and apoptosis index of hepatocyte (r=-0.65, P＜0.01). Conclusions The findings indicate that δ-opioid receptor agonists DADLE can obviously improve hepatic pathological changes of septic rats. And its protective mechanism contains down regulation of caspase-3 expression, upregulation of bcl-2 expression and thus the apoptosis of hepatocyte is repressed.
Sepsis is a worldwide problem. Although there are many related researchs and animal experiments about sepsis, the mortality of sepsis is still high. In the early stage of sepsis, after the pathogenic bacteria invade the body, the immune response produced by the body promotes the synthesis and secretion of a series of cytokines. Among them, there are proinflammatory cytokines that promote inflammatory response and anti-inflammatory cytokines that inhibit inflammatory response. These cytokines interact with each other and maintain a dynamic balance in complex cell grid. This is to restore the steady state of the body after resisting and eliminating the invaders.Anti-inflammatory cytokines play an important role in it. They act on specific immune cells or immune regulatory receptors. Anti-inflammatory cytokines limit persistent or excessive inflammatory responses after killing invaders, and reduce or block pro-inflammatory cytokine activities. These anti-inflammatory cytokines also can heal body to restore the normal immune physiological level of the organism. This article will review the related research of anti-inflammatory cytokines in sepsis.
Objective To study the effects of total saponins of panax notoginseseng injection on the coagulation function in sepsis. Methods 50 sepsis patients with normal coagulation function were randomly divided into two groups. 25 patients in the control group received the routine treatment and the other 25 patients in the treatment group received total saponins of panax notoginseseng injection additionally. The levels of Plt, PT, TT, APTT, FIB and D-D were measured before the therapy and on 1st, 3rd and 7th day after the therapy. Results The levels of Plt, PT, TT, APTT, FIB and D-D before the therapy had no significant differences between the two groups ( P gt; 0. 05) . The levels of Plt and FIB had significant differences between the two groups on 7th day after therapy ( P lt;0. 01, P lt; 0. 05) . PT, TT, and APTT were prolonged in the controlled group gradually, butwere not prolonged or even shortened in the treatment group,which were significantly shorter in the treatment group on 7th day after therapy ( P lt; 0. 05) . D-D slightly elevated in the control group, but slightly elevated at first and dropped gradually in the treatment group, which was significantly lower in the treatment group on7th day after therapy. Conclusion Total saponins of panax notoginseseng injection has a protective effect on coagulation function in sepsis.
Sepsis is a common complication after severe trauma, infection, shock and major surgery. It has the characteristics of high morbidity, high mortality, and high hospitalization costs. Septic cardiomyopathy is one of the main causes of death in patients with sepsis. This article reviews the pathogenesis and treatment of septic cardiomyopathy. The pathogenesis includes hemodynamics and myocardial changes, mitochondrial fission, cardiomyocyte apoptosis and autophagy, calcium ion imbalance, inflammation mechanism and immune regulation mechanism. The treatment includes conventional treatment, β1 receptor blocker treatment, melatonin, serotonin 3 receptor antagonist, dexmedetomidine and traditional Chinese medicine treatment, etc., aiming to provide a reference for the diagnosis and treatment of septic cardiomyopathy.
Objective To explore the predictive value of simplified acute physiological score Ⅱ (SAPS-Ⅱ) combined with lactate clearance rates (LCR) at different moments for mortality in sepsis patients. Methods A total of 188 patients with sepsis admitted in the hospital from April 2020 to February 2023 were selected, who were evaluated using the SAPS-Ⅱ scale. Spectrophotometry was used to detect blood lactate at baseline, after 6h, 12h, 24h, and 48h, then the LCR after 6h, 12h, 24h, and 48h were calculated. The patients were divided into a survival group (n=139) and a death group (n=37) based on 28 day outcome. Logistic regression analysis was used to explore the risk factors of sepsis death, and the efficacy of SAPS-Ⅱ scores combined with LCR at different moments in predicting patient death was analyzed using receiver operating characteristic (ROC) curve. Results Twelve patients fell off, and 37 died in the remaining 176 patients, the mortality rate was 21.02%. The age, temperature, random blood glucose, blood urea nitrogen, serum creatinine, and SAPS- Ⅱ scores in the death group were significantly higher than those in the survival group (P<0.05), while platelet count and LCR at all moments were significantly lower than those in the survival group (P<0.05). The LCR of the death group continued to decrease with time. The trend of changes in the survival group were opposite, and the differences in the two groups between each two moments were statistically significant (P<0.05). The SAPS-Ⅱ scores and LCR at all moments were risk factors for patient death (P<0.05). The SAPS-Ⅱ score and LCR at all moments had predictive value for patient death, and the area under ROC curve of the combined prediction was 0.921 (95%CI 0.825 - 1.000), which was higher than the individual prediction and LCR at each moment combined with SAPS II score prediction (P<0.05). Conclusion The SAPS-Ⅱ scores and LCR at different moments are all related to death of sepsis patients, and the combined prediction of death by the above indicators is highly effective.