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.
ObjectiveTo investigate the distribution and content of endogenous salusin-βin septic rats. MethodsThirty-six SPF male SD rats were randomly divided into sham operation group (n=9) and septic model group (n=27).Only the cecum was turn in the sham operation group and the septic model was made by the cecal ligation and puncture (CLP) in the septic model group.The rats were sacrificed at 6 h, 12 h, and 24 h after modeling in the septic model group.The contents of salusin-βin the tissues of spleen, stomach, small intestine, hypothalamus, and serum specimens were detected by enzyme-linked immunosorbent assay. Results①The salusin-βendogenously generated in the rat tissues including the spleen, stomach, small intestine, hypothalamus, and serum.The content of salusin-βin the spleen tissue was higher than that in the other tissues (P < 0.05).②The contents of salusin-βin the spleen, stomach, small intestine tissues together with the serum increased significantly at 6 h after CLP as compared with the sham operation group (P < 0.05).The contents of salusin-βin the spleen tissue and serum were peaked at 12 h, in the small intestine tissue reached the summit at 24 h.While, the content of salusin-βhad no significant fluctuation in the stomach tissue.The content of salusin-βbegan to increase at 6 h in the hypothalamus tissue, and significantly increased at 12 h after CLP (P < 0.05). ConclusionThe time-dependent change of salusin-βin sepsis rats suggests that salusin-βmight be involved with the pathogenesis of sepsis.
Objective To compare the vasoactive effects of norepinephrine( NE) and dopamine of different doses on isolated rabbit pulmonary and systemic arteries in septic shock. Methods Six paired pulmonary and systemic arterial rings were prepared fromsix rabbits, and matched randomly assigned into a normal group and a LPS group. The assigned groups were intervened by different doses of NE. Another six paired pulmonary and systemic arterial rings were prepared from another six rabbits. They were assigned to different groups as above and intervened by different doses of dopamine. The LPS groups were pre-incubated in RPMI mediumsupplemented with4 μg/mL LPS to simulate septic shock. The tension of arterial rings was measured and its response to NE and dopamine were studied. Results ( 1) In the normal groups, the contraction of the systemic arteries was ber than the pulmonary arteries in response to low,middle dose of NE, and high dose of dopamine ( all P lt; 0. 05) , and which was weaker in response to middle dose of dopamine and similar in response to high dose of NE( P gt;0. 05) . Both the pulmonary and systemic arteriesrelaxed in response to low dose of dopamine. ( 2) After LPS pre-incubation, the contraction of the systemic arteries was weaker than the pulmonary arteries in response to low dose of dopamine ( P lt;0. 05) , and which was similar in response to low,middle and high dose of NE, and middle, high dose of dopamine. ( 3) Comparing the LPS groups with the normal groups, the contraction in response to middle dose of dopamine increased in the systemic arteries and dreased in the pulmonary arteries ( P lt;0. 05) . Conclusions In septic shock, the vasoactive effect of different doses of NE is not different between pulmonary and systemic arteries. But middle dose of dopamine can increase the contraction of systemic arteries and decrease the contraction of pulmonary arteries.
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 explore the clinical significance of the platelet glycoproteins CD62p and CD63 in septic patients.Methods The expressions of CD62p and CD63 in peripheral platelet were measured in 40 septic patients within 24 hours after onset by flow cytometry.The expression levels of CD62p and CD63 in mild and severe sepsis and normal subjects were compared.Meanwhile the correlation of CD62p and CD63 with APACHE Ⅱ score was analyzed.Results Significant differences in the CD62p and CD63 levels were found in the septic patients when compared with the normal subjects [CD62p：（2.56±1.51）% vs （1.48±0.40）%；CD63：（2.15±0.50）% vs （1.29±0.35）%；all Plt;0.01].The expressions of CD62p and CD63 in the severe septic patients were significantly higher than those in the mild septic patients [CD62p：（3.31±1.94）% vs （2.05±0.87）%；CD63：（2.37±0.36）% vs （2.00±0.53）%；all Plt;0.05].The positive correlations of CD62p and CD63 with APACHE Ⅱ score were also found（CD62p：r=0.377，P=0.016；CD63：r=0.452，P=0.003）.Conclusion Platelets were significantly activated in septic patients at early stage which was correlated with 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.
ObjectiveTo investigate the clinical value of soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) for diagnosis and prognosis of sepsis. MethodsPatients with SIRS (n=58) were divided into a sepsis group (n=40) and a non-sepsis group (n=18),and 12 healthy adults were admitted as control. Serum concentrations of sTREM-1,interleukin-6 (IL-6) and IL-10 were measured on days 1,3,7 and 14 by ELISA. According to the survival on 28th day after admission,the sepsis group was divided into survivors (n=27) and non-survivors (n=13). APACHEⅡ score and SOFA score were used to evaluate the severity of sepsis. The correlations between sTREM-1 and IL-6,IL-10,disease progression or prognosis were analyzed respectively. ResultsOn the first day of enrollment,sTREM-1,IL-6 and IL-10 [217.28(136.02-377.01) pg/mL,218.76(123.32-548.58) pg/mL and 93.86(54.23-143.1) pg/mL,respectively] in the sepsis group were significantly higher than those in the non-sepsis group [55.51(39.50-77.33) pg/mL,75.98(34.89-141.03) pg/mL and 52.49(45.66-56.72) pg/mL,respectively] and the control group [43.99(36.28-53.81) pg/mL,46.07(40.23-53.72) pg/mL and 49.79(43.31-53.14) pg/mL, respectively] (All P<0.01). For diagnosis of sepsis,the area under the curve (AUC) for sTREM-1 was 0.82 (95%CI 0.70-0.94). Levels of sTREM-1 and IL-10 in survivors of sepsis were gradually increased on 1st,3rd,7th day of enrollment,while level of sTREM-1 in non-survivors showed an obvious decrease during the observation. On the 14th of admission,sTREM-1,IL-6,IL-10 and IL-6/IL-10 ratio of non-survivors were significantly higher than those of survivors (P<0.05). There were significantly positive correlations between sTREM-1 and APACHEⅡ score,SOFA score,IL-6,IL-10 or IL-6/IL-10 ratio (r=0.624,0.454,0.407 and 0.324,respectively,all P<0.05). Logistic regression analysis indicated that serum level of sTREM-1 may be used as a prognostic factor of sepsis,but not an independent risk factor. ConclusionSerum sTREM-1 could be used as a marker to detect sepsis early,and sTREM-1 is also involved in systemic inflammatory reaction of sepsis patient and appears to be a prognostic value of sepsis.