ObjectiveTo investigate the effects of epinephrine in intestinal injury caused by lipopolysaccharide (LPS) in rats.MethodsFifty SD rats were randomly divided into five groups ( n =10 pet group ):saline control group received intravenous infusion of 0.9％ saline 2.4 ml/( kg· h) ;LPS group received intravenous injection of LPS 6 mg/kg;small-dose,medium-dose,and large-dose epinephrine treatment group received an intravenous infusion of epinephrine 0.12 μg/(kg· min),0.3 μg/( kg· min),and 0.6 μg/( kg· min)after LPS 6 mg/kg intravenous injection,respectively.Intestinal injury was evaluated by intestinal pathological examination.Blood samples were taken at 0,2 and 6 h after LPS infection,and the levels of serum TNF-α,IL-1β and IL-10 were detected by enzyme-linked immunoadsorbent assay.The pathological changes of intestine were observed at 24 h.ResultsPathological examination showed that LPS caused severe congestion,edema,neutrophil infiltration,hemorrhage and cell necrosis in intestine.Compared with LPS group,large-dose epinephrine ameliorated the damage of intestine.In LPS group,serum levels of TNF-α[ ( 1164 ± 145) ng/L],IL-1β[ (521 ±68) ng/L],IL-10 [ (303 ±20) ng/L] all increased compared with control group (P＜0.05)at 2 h.Compared with LPS group,serum levels of TNF-α[ (576 ± 105) ng/L] were significantly depressed (P＜0.05),whereas IL-10 was elevated at 2 h[ (424 ±29) ng/L] and6 h[ (245 ± 14) ng/L] (P＜0.05)in large-dose epinephrine treatment group.Serum IL- 1β levels were unaffected by large-dose epinephrine treatment.Small-dose and medium-dose epinephrine could not reduce the pathological injury of intestine induced by lipopolysaccharide.Compared with LPS group,levels of serum TNF-α,IL-1β and IL-10 were also unaffected by small-dose and medium-dose epinephrine treatment ( all P＞0.05 ) at any time points.ConclusionEpinephrine reduced the intestine injury caused by LPS by down-regulating pro-inflammatory cytokines production and up-regulate anti-inflammatory cytokines production.

Uncoupling protein 2(UCP2)is a proton transporter which presents in the mitochondrial inner membrane. Recent studies have found that UCP2 plays important roles in protecting mitochondria functions,re-ducing mitochondrial ROS generation by inducing proton leak across the inner mitochondrial membrane and pro-moting mild uncoupling which leading to a decrease in the mitochondrial inner membrane′s potential. Because of its antioxidant function,UCP2 has been studied in several domains. This review provides novel insights into the molecular mechanisms,by which the activity of UCP2 is regulated and describe novel findings concerning basical experiments of UCP2.

Objective To investigate the protective effect and possible mechanisms of continuous infusion of norepinephrine in kidney of septic rats in the early stage.Methods Thirty healthy male SD rats of SPF level were randomly divided into five groups.Rats in control group were given intraperitoneal injection of saline and began a continuous infusion of saline (1 ml/h).Rats in LPS group and the intervention group (low-dose,medium-dose and high-dose norepinephrine group) were given intraperitoneal injection of LPS 10 mg/kg.LPS group began a continuous infusion of saline (1 ml/h) while low,medium and high dose groups began continuous infusion of different norepinephrine solution [(0.06,0.3,0.6 μg/(kg·min)].Rats were sacrificed after 24 hours infusion.We detected serum inflammatory cytokines [tumor necrosis factor (TNF)-α,interleukin(IL)-1β,IL-6 and IL-10] in 2 h and 6 h by ELISA.Rat serum CRP,Cr and BUN,swelling and membrane potential of kidney mitochondria and oxidative stress-related indicators were tested in 24 h.We also observed renal pathologic changes by electronic microscopy and biopsy.Results Compared with the control group,serum levels of TNF-α [(2 203.3 ± 1 028.7) pg/ml],IL-1β [(2 214.5 ±457.0) pg/ml],IL-6 [(7784.7 ±248.2) pg/ml] and IL-10 [(1 076.1 ±368.4) pg/ml] were statistically higher in LPS group in 2 h (P ＜ 0.05) ; CRP [(0.35 ± 0.24) mg/L],Cr [(30.8 ± 11.5) μ mol/L],BUN [(7.7 ± 1.8) mmol/L],NO [(1 057.4 ± 172.9) μmol/gprot] were statistically higher (P ＜ 0.01),membrane potential of kidney mitochondria (0.0464 ±0.018 5) decreased statistically (P ＜0.01).Compared with LPS group,serum levels of TNF-αt [(506.8 ±301.7) pg/ml],IL-lβ [(415.6 ± 178.0) pg/ml],and IL-10 [(381.7 ± 171.0) pg/ml] significantly decreased in low-dose group in 2 h (P ＜0.05),BUN [(5.2 ± 1.4)mmol/L] decreased (P ＜ 0.05),mitochondrial membrane potential (0.347 4 ± 0.152 6) increased in 24 h (P ＜ 0.05) ; serum levels of TNF-α [(323.9 ± 227.9) pg/ml],IL-1 β [(700.0 ± 246.2) pg/ml],and IL-10[(282.6 ± 134.4) pg/ml] significantly decreased statistically in medium-dose group in 2 h (P ＜0.05),CRP [(0.17 ± 0.08) mg/L] decreased statistically (P ＜ 0.01),mitochondrial membrane potential (0.377 5 ±0.143 7) increased in 24 h (P ＜0.05) ;serum levels of TNF-α [(378.7 ±89.8) pg/ml],IL-1β [(945.7 ±264.4) pg/ml] significantly decreased in high-dose group in 2 h (P ＜0.05),CRP [(0.19 ±0.12) mg/L] and Cr [(23.2 ±3.4) μmol/L] decreased in 24 h (P ＜0.05).Mitochondrial matrix coated fuzzy,vacuoles and coagulation were found in LPS group by electronic microscopy examination.Interstitial edema,monocyte-macrophage infiltration,glomerular shrinkage,tubular epithelial cell swelling,empty bubble degeneration were found in LPS group by microscopy examination.Pathological damage was alleviated in mediumdose group.Conclusion Continuous infusion of norepinephrine plays a protective role on renal function in rats with sepsis in the early stage.The intervention protect rat kidney by reducing levels of inflammatory cytokines,oxidative stress and mitochondrial damage.

Objective To observe the effect of Xingnaojing injection in myocardial mitochondrial oxidative stress injury in sepsis mice. Methods The septic model were set up by receiving endotoxin through interaperitoneal injection. After Xingnaojing injection by gastric tube , seventy mice were randomly divided into 7 groups in ten of each group including group LPS-6 h , group LPS-24 h , group LPS-48 h; group XNJ-6 h , group XNJ-24 h, group XNJ-48 h and control group. The myocardial mitochondrial changes , the semi-quantitative scores and the level of SOD、MDA、NO、iNOS in sepsis mice were observed. Results Xingnaojing injection could improve the myocardial mitochondrial changes , reduce the semi-quantitative scores , significantly reduce the level of MDA、NO、iNOS and elevate the level of SOD. Conclusion Xingnaojing injection could significantly reduce the myocardial mitochondrial oxidative stress level and improve the ability of clearing oxygen radicals , thereby protect the myocardial mitochondrion in sepsis mice.

Objective To investigate the protective effects of continuous norepinephrine infusion and its mechanism in early stage of lipopolysaccharide induced septic rats.Methods Forty SD rats were randomly divided into 5 groups (an external jugular vein catheterization was performed in every rat a day before intraperitoneal injection):saline control group (n =8),endotoxin group (n =8),low dose norepinephrine therepy group(n =8),middle dose norepinephrine therepy group (n =8),and high dose norepinephrine therepy group (n =8).Saline control group received intraperitoneal injection of 0.9％ saline 10 ml/kg,and then received an infusion of 0.9％ saline 1 ml/h.Endotoxin group animals were intraperitoneal injected with lipopolysaccharide 10 mg/kg,and then received an infusion of 0.9％ saline 1 ml/h.Therapy group animals received an infusion of norepinephrine solution 1 ml/h after being intraperitoneal injected LPS 10 mg/kg.The doses of norepinephrine were 0.06,0.3,0.6 μg/(kg· min) respectively.Blood samples were taken 2 h and 6 h later and the levels of serum TNF-α、IL-1β and IL-10 were detected by enzyme-linked immunoadsorbent assay.The membrane potential and three tricarboxylic acid cycle key enzyme activity [isocitrate dehydrogenase(IDH) and pyruvate dehydrogenase (PDH) activity] of isolated liver mitochondrion were detected 24 h later,and the morphologic changes of mitochondria in liver were observed by electronic microscopy.Results In endotoxin group,the levels of serum TNF-α JL-1 β and IL-10 all increased significantly(P ＜ 0.05) and liver mitochondrial membrane potential,PDH and IDH activity decreased significantly compared with control group(P ＜0.05,P ＜0.01).In the middle dose of norepinephrine therepy group,the levels of serum TNF-α and IL-1β all increased significantly (P ＜ 0.05,P ＜ 0.01),the level of serum IL-10 decreased significantly compared with endotoxin group (P ＜ 0.05) ; In the high dose norepinephrine therepy group,the liver mitochondrial membrane potential,PDH and IDH activity increased significantly compared with endotoxin group (P ＜ 0.05).The mitochondrial ultrastructural changes in every group were not obviously.Conclusion In the early stage of septic rats,reversible liver mitochondrion injury can be observed.Norepinephrine infusion can protect early septic rats through attenuating inflammatory reaction and enhancing tricarboxylic acid cycle key enzyme activity and mitochondrial membrane potential level.

Sepsis associated encephalopathy (SAE)is the most common form of encephalopathy in the pediatric intensive care units and might appear before other systemic features of sepsis.The pathogenesis of SAE is complex and not clear.SAE causes increased morbidity and mortality but has limited therapeutic options.SAE has become a hot issue in critical care medicine.

Multiple organ dysfunction syndrome(MODS),a hot topic worldwide,has made rapid progress with nigh mortality.MODS in pediatrics versus MODS in adults are similar but different.Due to special age-related physiological characteristics.It is difficult to carry out randomized controlled clinical study compared with adults.Diagnosis and treatment of pediatric MODS can only be obtained with reference to adult MODS.This study reviews on the epidemiology,clinical scoring system,pathogenesis,clinical features and treatment of MODS in pediatrics.

Sepsis is a life-threatening organ dysfunction caused by dysregulation of the host response due to infection, and it can further develop into septic shock.Currently, sepsis is still a leading cause of death in children all over the world.Therefore, early assessment of the severity and prognosis of sepsis is of great significance.However, there are no indexes with high sensitivity and specificity for evaluating the severity and prognosis of sepsis at present.In recent years, a large number of studies have revealed the essential role of platelets in sepsis.It has been reported that the platelet count is an independent factor affecting the severity and prognosis of sepsis patients.Up to now, the specific mechanism of sepsis-induced thrombocytopenia has not been fully clarified.In this review, the value of thrombocytopenia in predicting the severity and prognosis of sepsis patients was elaborated.

Objective To investigate the effects of epinephrine in sepsis-associated lung injury in rats. Methods Thirty SD rats were randomly divided into three groups(n =10 per group):control group received intravenous 0. 9% saline 2. 4 ml/( kg·h ); LPS group received intravenous LPS ( 6 mg/kg ); epi-nephrine treatment group received an infusion of epinephrine 0. 6μg/( kg·min) after LPS intravenous injec-tion . Blood samples were taken at 2 h and 6 h after LPS injection and the levels of serum tumor necrosis factor ( TNF)-α,interleukin( IL)-6 and IL-10 were detected. The rats were sacrificed at 6 h. The lung tissues and bronchoalveolar lavage fluid( BALF) were collected. Pathological changes of the lung tissues were observed under light microscope. Water content of lung,expression of TNF-α,IL-6 and IL-10 in BALF and in serum were detected. Results (1) The water content of lung in LPS group significantly increased compared with that in control group(85. 24% ± 5. 87% vs. 70. 19% ± 5. 87%) and epinephrine group(78. 00% ± 6. 41%) (P<0. 05). (2)Pathological examination showed that LPS could cause pulmonary capillary hyperemia,ede-ma,inflammatory cells infiltration. Atelectasis and alveolar edema were found in small number of lung tissue. Compared with LPS group, epinephrine ameliorated the lung pathological injury. ( 3 ) Compared with LPS group,serum levels of TNF-α and IL-6 significantly decreased ( P <0. 05 ) , whereas IL-10 increased ( P <0. 05) in epinephrine group. (4)Compared with LPS group,BALF levels of TNF-α[(78 ± 9)ng/L vs. (102 ±16)ng/L]andIL-6[(268±42)ng/Lvs.(347±50)ng/L]significantlydepressed(P<0.05),whereas BALFlevelsofIL-10[(210±23)ng/Lvs.(146±34) ng/L]elevated(P <0.05) inepinephrinegroup. Conclusion Epinephrine could reduce the acute lung injury caused by LPS. Its protective effect may be re-lated to decreasing the levels of TNF-α and IL-6,elevating IL-10 level.

ObjectiveTo investigate the effects of autophagy on exocrine function of pancreas in rats with acute sepsis, and to determine whether the mitochondrial coenzyme Q (Mito Q) can prevent exocrine dysfunction of pancreas mediated by autophagy.Methods ExperimentⅠ: 30 Sprague-Dawley (SD) rats were randomly divided into three groups, with 10 rats in each group. All the rats were given lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally, and Wortmannin (2 mg/kg), the specific inhibitor of autophagy (LPS+ Wortmannin group), Mito Q (6.5μmol/kg, LPS+Mito Q group), or the same volume of normal saline (LPS group) was respectively injected via the tail vein 1 hour later. Survival rate was assessed within 12 hours after LPS injection. ExperimentⅡ: another 100 male SD rats were randomly divided into ten groups with 10 rats in each group: namely control 4, 6 and 12 hours groups, LPS 4, 6 and 12 hours groups, and LPS+ Wortmannin 4 hours group, Wortmannin 4 hours group, LPS+ Mito Q 6 hours group, and Mito Q 6 hours group. The protocols of model reproduction and drug administration were the same as in the experimentⅠ. Blood samples were collected at each time point, and the amylase content was determined with the velocity method. The levels of reactive oxygen species (ROS) in the pancreases were measured with enzyme-linked immunosorbent assay (ELISA). The expression of the autophagy-related protein LC3 was determined with Western Blot. The pathological changes in the pancreas were observed with microscopy.Results① The survival time in the LPS+ Wortmannin group was significantly shorter than that in the LPS group (hours: 7.50±0.64 vs. 11.90±0.13,χ2= 19.847,P= 0.001). There was no significant difference in the survival time between LPS+ Mito Q and LPS groups (hours: 11.60±0.24 vs. 11.90±0.13,χ2= 1.055,P= 0.137).② The serum amylase in the LPS 6 hours, LPS+ Wortmannin 4 hours, and LPS+ Mito Q 6 hours groups were significantly higher than those in the control group at the same time points (U/L:2 881.00±550.12 vs. 2 099.20±249.57, 3 672.00±779.24 vs. 2 081.36±245.18, 2 975.20±687.03 vs. 2 099.20± 249.57, allP< 0.05), and were significantly lowered in LPS 12 hours group (U/L: 794.00±218.71 vs. 2 086.80±261.75, P< 0.01). The pancreatic ROS in the LPS 6 hours and 12 hours groups, LPS+ Wortmannin 4 hours group, and LPS+Mito Q 6 hours group were significantly higher than those of the control group at the same time points (kU/L: 3.18±1.06 vs. 1.78±0.37, 3.63±1.08 vs. 1.85±0.41, 3.14±0.98 vs. 1.65±0.34, 3.17±1.03 vs. 1.78±0.37, allP< 0.05). The serum amylase and pancreatic ROS in LPS+ Wortmannin 4 hours group were significantly higher than those of the LPS group at the same time points (U/L: 3 672.00±779.24 vs. 2 432.20±442.85, kU/L: 3.14±0.98 vs. 1.87±0.42, both P< 0.05), but there were no differences in above two parameters between LPS+ Mito Q 6 hours group and LPS group (U/L: 2 975.20±687.03 vs. 2 881.00±550.12, kU/L: 3.17±1.03 vs. 3.18±1.06, bothP> 0.05). Light microscopy showed that obvious pathological changes were found in the pancreas in the LPS 6 hours and 12 hours groups, LPS+Wortmannin 4 hours group, and LPS+ Mito Q 6 hours group. Electron microscopy showed that the number of autophagic vacuoles increased 6 hours after LPS administration. There was no difference at any time point in the number of autophagic vacuoles between LPS+ Mito Q 6 hours group and LPS 6 hours group, and the autophagic vacuoles were not found after Wortmannin intervention. It was demonstrated by Western Blot that the levels of LC3 protein in the LPS 6 hours and 12 hours groups, and LPS+ Mito Q 6 hours group were significantly higher than those of the control group at the same time points (A value: 0.34±0.02 vs. 0.17±0.02, 0.37±0.03 vs. 0.18±0.04, 0.36±0.02 vs. 0.17±0.02, allP< 0.05), but there were no differences between LPS 12 hours group or LPS+ Mito Q 6 hours group and LPS 6 hours group (bothP> 0.05).Conclusions Autophagy prevents exocrine dysfunction of pancreas in septic rats, and the autophagic capacity or autophagosome-formation rate may determine the development of exocrine pancreatic dysfunction. The mitochondria-targeted antioxidant Mito Q does not prevent exocrine dysfunction of pancreas.