Objective To investigate the effects of simvastatin on lung tissue in septic rats by observing the protein expression of nuclear factor kappa B ( NF-κB) and pathologic changes in lung tissue at different time points. Methods 90 healthy male Sprague-Dawley rats were randomly divided into three groups ( n =30 in each group) . All the rats received administration by caudal vein and capacity volume is 2 mL. The rats in the control group were treated with saline ( 2 mL) . The rats in the LPS group were treated with LPS ( 5 mg/kg ) . The rats in the simvastatin group were treated with LPS ( 5 mg/kg) and simvastatin ( 20 mg/kg) . Six rats in each group were killed randomly at 2, 4, 6, and 12 hours after the injection, and the right middle lobe of lung was taken out. Pathological changes of lung tissue wee investigated under light microscope. The expression of NF-κB in lung tissue was determined by immunohistochemistry ( IHC) method. Results Microscopic studies showed that there were not pathological changes in the lung tissue of rats in the control group. While in the LPS group, the alveolar spaces were narrowed and the alveolar wall were thickened. Furthermore, severe interstitial edema of lung and proliferation of epithelial cells were observed. In the simvastatin group, the degree of the infiltration of leukocytes and the lung interstitial edema were less severe than those in the simvastatin group. In the control group, the expression of NF-κB protein in most of lung tissue was negative. In the LPS group, the expression of NF-κB protein was detected at 2h, andreached the peak at 6h, then decreased at 12h. In the Simvastatin group, the NF-κB expression was significantly lower than that in the LPS group at all time points ( P lt; 0. 01) . Conclusion Simvastatin can ameliorate pathological lesions and decrease expression of NF-κB in lung tissue of septic rats.
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.
Objective To investigate the efficacy of continuous blood purification ( CBP) in the treatment of severe sepsis, and explore the related immune regulatory mechanisms. Methods Forty-eight patients with severe sepsis were randomly divided into a control group ( n =23) and a CBP group ( n =25) .CD4 + CD25 + regulatory T cells ( Treg% ) in peripheral blood and APACHEⅡ score were measured dynamically before treatment and 12, 24, 36, 48, 60, 72 hours after treatment. Meanwhile the length of ICUstay, duration of mechanical ventilation, and 28 day mortality were determined. Results Compared with the control group, the length of ICU stay, ventilator time, incidence of multiple organ failure, and mortality decreased significantly in the CBP group ( P lt; 0. 05) . And CBP also decreased Treg% and APACHEⅡ score significantly. There was a positive correlation between Treg% and APACHEⅡ score ( r =0. 804, P lt;0. 01) .Conclusion Early CBP treatment can reduce Treg%, improve cellular immunity and improve the prognosis of sepsis.
ObjectiveTo investigate the protective effects of diisopropylamini dichlorocacetas on impairment of hepatic function in patients with sepsis. MethodsThe 60 inpatients with liver dysfunction and sepsis treated in our hospital between June 2010 and December 2012 were randomly divided into two groups: treatment group (n=30) and control group (n=30). In the treatment group, patients were treated with intravenous diisopropylamini dichlorocacetas for 7 days, while patients in the control group were treated with Vitamin C for the same period. The venous blood sample of each patient of the two groups was collected and examined for the content of alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, alkaline phosphatase, total bilirubin, and direct bilirubin before and after treatment, and the effective rates of the two groups were determined. ResultsLiver function indicators after treatment of both the two groups were reduced. Compared with the control group, the liver function indicators were significantly decreased and the total effective rate was significantly higher in the treatment group (P<0.05). ConclusionDiisopropylamini dichlorocacetas is effective in the treatment of impairment of hepatic function in patients with sepsis.
Objective To investigate the value of extravascular lung water index ( EVLWI) and intrathoracic blood volume index ( ITBVI) monitoring in fluid management of severe pneumonia patients with sepsis shock.Methods A prospective controlled study was conducted in106 patients who were diagnosed as severe pneumonia with sepsis shock in intensive care unit fromJanuary 2010 to February 2013. 54 patients who received pulse indicator continuous output ( PiCCO) monitoring were enrolled into the EVLWI + ITBVI group, and EVLWI and ITBVI were used as indicator of fluid management. 52 patients who received central venous pressure ( CVP) as indicator of traditional fluid managementwere enrolled into the control group. The time and the rate to achieve early goal-directed therapy ( EGDT) target were compared between two groups. Acute physiology and chronic health evaluation Ⅱ ( APACHE Ⅱ ) , sepsis related organ failure assessment ( SOFA) , noradrenaline dosage, serumlactic acid, serum creatinine were compared between 1 day and 3 days after treatment. The characteristics of fluid management were recorded and compared within 72 hours. Mechanical ventilation ratio, duration of mechanical ventilation, ICU stay and 28-day mortality were compared between two groups. Results The ratio of achieving EGDT target in 6 hours was significantly higher in the EVLWI + ITBVI group than that in the control group ( 75.9% vs. 55.7% , Plt;0.05) , whereas the time and the ratio to achieve EGDT target in 24 hours were not statistically different. APACHE Ⅱ, SOFA, norepinephrine dosage, serum lactate were significantly decreased 3 days after treatment in the EVLWI + ITBVI group, but did not change significantly in the control group. On3 days after treatment, serumcreatinine was increased in the control group, and did not change significantly in the EVLWI + ITBVI group. The fluid intake and fluid balance volume during 0-6 hours period were significantly higher in the EVLWI + ITBVI group than those in the control group ( Plt;0.05) , but showed no difference ( Pgt;0.05) in other periods. Mechanical ventilation ratio, duration of mechanical ventilation, ICU stay and 28-days mortality were significantly lower in the EVLWI + ITBVI group compared with the control group ( Plt;0.05) . Conclusion Compared with CVP, ITBVI and EVLWI can more accurately assess and guide fluid management in severe pneumonia patients with septic shock with less duration of mechanical ventilation, ICU stay and mortality.
Objective To investigate the relationship between blood CD4 + CD25 + regulatory T cells ( Treg cells) and cell immunity in patients with sepsis and its prognostic value.Methods 27 patients with sepsis admitted during August 2007 and August 2008 in ICU were enrolled, while 40 healthy volunteers served as control. According to the clinical outcome after 28 days’ treatment, the sepsis patients were assigned to a death group( n=8) and a survival group ( n =19) . Blood Treg% and CD4 /CD8 were detected by flow cytometry and total AgNOR area/nucleus area per cell ( IS%) was measured by silver nitrate staining and image processing. Results The Treg% in the patients with sepsis was significant higher than that in the normal control [ ( 5. 61 ±1. 60) % vs. ( 0. 78 ±0. 23) % , P lt; 0. 01 ] , while the level of CD4 /CD8 and IS% were significant lower[ CD4 /CD8: ( 1. 09 ±0. 30) vs. ( 1. 71 ±0. 36) , IS% : ( 5. 19 ±1. 07) % vs. ( 6. 76 ±0. 92) % , both P lt; 0. 01] . Significant correlations were found between Treg% and CD4 /CD8( r= - 0. 484, P lt;0. 01) , and between Treg% and IS% ( r = - 0. 588, P lt;0. 01) . Compared with the survival group, Treg% was significant higher [ ( 7. 09 ±1. 17) % vs. ( 5. 00 ±1. 33) % , P lt; 0. 01] , and CD4 /CD8 and IS% were significant lower[ CD4 /CD8: ( 0. 87 ±0. 22) vs. ( 1. 18 ±0. 29) , IS% : ( 3. 97 ±0. 42) % vs. ( 5. 71 ±0. 81) % , both P lt; 0. 01] in the death group. Conlusion Blood Treg% level can reflect the cell immune state of patients with sepsis and is of clinical value to assess the prognosis.
ObjectiveTo evaluate the clinical efficacy of fish oil containing lipid emulsion (FO) in sepsis. MethodsRandomized controlled trials about fish oil containing lipid emulsion in sepsis,which were published from 1980,were searched from the following electronic databases:PubMed,Embase,Foreign Medical Journal Service,Cochrane Library,CNKI,Wanfang Database,and VIP Database. The articles screening,quality assessment and data extraction were conducted by two reviewers independently. The methodological quality of trials was assessed by Jadad's scale. All data was analyzed by Review Manager 5.2 software. ResultsFifteen studies involving 794 participants met the inclusion criteria. The meta-analysis results were as follows:compared with the control group,①FO could shorten the length of ICU stay[WMD=-5.59,95%CI(-7.65,-3.53)] and the length of hospital stay[WMD=-10.48,95%CI(-14.67,-6.29)],and also decrease the 28-day mortality[RR=0.69,95%CI(0.52,0.93)]. ②FO could reduce the concentration of TNF-α[WMD=31.78,95%CI(5.63,57.92)] and improve oxygenation index[WMD=41.95,95%CI(30.80,53.11)] in septic patients. ③There was no statistical significance in the decrease of C-reactive protein (CRP) between two groups(P>0.05). ConclusionThe administration of FO in septic patients can significantly shorten the length of ICU stay and hospital stay,decrease the 28-day mortality,reduce the concentration of TNF-α and improve oxygenation index. However,it shows no significant difference in the decrease of CRP compared with the administration of traditional lipid emulsion. All of the above results show that the septic patients can benefit from the administration of fish oil containing lipid emulsion.
【Abstract】 Objective To study the effects of glutamine (Gln) combined with growth hormone （GH） on the levels of cytokine (TNF-α, IL-1, IL-6), coritsol and amino acid metabolism in septic rats. Methods Ten out of 79 SD rats were randomly collected as the control group. Thirty of 69 septic SD rats, which were made by cecal ligation and perforation (CLP) method and were given parenteral nutrition (PN) lived to day 6. They were also randomly divided into three groups as follows: septic group (n=10), parenteral supplemented glutamine group (Gln group, n=10), and Gln combined with GH (Gln+GH group, n=10). On the 6th day, blood drew from portal veins of the dead rats was used to detect the levels of TNF-α， IL-1， IL-6 and cortisol by ELISA. The plasma concentrations of free amino acids were determined by amino acid auto-analyzer. The muscle tissue of extensor digitorum longus was used to determine 3-methyl-histidine (3-MH) by high performance liquid chromatographic (HPLC). Results Except for the control group, most rats developed celiac abscess, hepatic abscess and pulmonary infection. The serum levels of TNF-α, IL-1, IL-6 and cortisol were significantly higher in the septic group than those of the other three groups, and they were significantly lower in the Gln+GH group than those of the Gln group, P＜0.05. Compared with the other three groups, the concentration of total amino acid in the septic group increased more, among which the glutamine and the branched chain amino acids were prominent. Most of concentrations of the amino acids decreased in the Gln group and the Gln+GH group, and the decreased amplitude of the Gln+GH group was larger, P＜0.05, albeit its level of Gln markedly increased. The concentration of 3-MH in muscle tissue was the highest in septic group, and it was significantly higher in the Gln group than that of the Gln+GH group, P＜0.01. ConclusionIt may be necessary to supplement GH combined with Gln as the content of PN to decrease cytokine levels and im-prove amino acid metabolism for septic case.
Objective To explore the effect of IL-10 on the inhibition of early proinflammatory cytokine release in intraabdominal infection and early sepsis. Methods Forty eight SD rats were randomized into 4 groups, 12 in each group, ①sham operation group, ②control group, ③prophylactic group, ④therapeutic group. Group 1 underwent laparotomy only, group 2 received laparotomy and cecal ligation plus punctures (CLP) with saline injected once every 3 hrs, group 3 underwent CLP and IL-10 injection intraperitoneally 1 hr before surgery and once every 3 hrs following operation, group 4 received CLP and IL-10 injection once every 3 hrs after operation. At 3 and 9 hr points, rats were sacrificed and blood samples were taken for measurement of inflammatory cytokines. Results Almost no inflammatory cytokines were detected in sham group, CLP produced a significant rise in serum TNF-α (tumor necrosis α), IL-1, IL-6 (interleukin 1,6) in control group, IL-10 reduced the rise of inflammatory cytokines significantly. Conclusion IL-10 could inhibit the early inflammatory cytokine release in rat model of sepsis. Suggesting it may attenuate the severity of inflammation.
Objective To explore independent risk factors for 30-day mortality in critical patients with pulmonary infection and sepsis, and build a prediction model. Methods Patients diagnosed with pulmonary infection and sepsis in the MIMIC-Ⅲ database were analyzed. The CareVue database was the training cohort (n=934), and the Metavision database was the external validation cohort (n=687). A COX proportional hazards regression model was established to screen independent risk factors and draw a nomogram. We conducted internal cross-validation and external validation of the model. Using the receiver operator characteristic (ROC) curve, Calibration chart, and decision curve analysis, we detected the discrimination, calibration, and benefit of the model respectively, comparing with the SOFA scoring model. Results Age, SOFA score, white blood cell count≤4×109/L, neutrophilic granulocyte percentage (NEU%)>85%, platelet count (PLT)≤100×109/L, PLT>300×109/L, red cell distribution width >15%, blood urea nitrogen, and lactate dehydrogenase were independent risk factors. The areas under the ROC curve of the model were 0.747 (training cohort) and 0.708 (external validation cohort), respectively, which was superior to the SOFA scoring model in terms of discrimination, calibration, and benefit. Conclusion The model established in this study can accurately and effectively predict the risk of the disease mortality, and provide a visual assessment method for early identification of high-risk patients.