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.

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.

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 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 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.

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.

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.

Objective To research the protective effect of insulin(IN)on lipopolysaccharide(LPS)- induced impairments of rat cardiomyocytes H9c2,and the role of uncoupling protein 2(UCP2)in this process. Methods Using randomized controlled grouping,after cultured for 24 h,H9c2 cells were randomly divided into 5 groups as follows:con-trol group,LPS stimulation group(LPS group),LPS + 70 IU/ L IN group(IN 70 IU/ L group),LPS + 350 IU/ L IN group(IN 350 IU/ L group),and LPS + 700 IU/ L IN group(IN 700 IU/ L group). H9c2 cells in IN group were treated with 70 IU/ L,350 IU/ L or 700 IU/ L IN 15 min before LPS stimulation,and H9c2 cells in control group were treated with an equal volume of saline. After that,cells in group LPS and IN were treated with LPS for 24 h. Lactate dehydro-genase(LDH)in the culture was determined with LDH detecting assay kit. The activity of reactive oxygen species (ROS)and superoxide dismutase(SOD),and content of malonaldehyde(MDA)were determined by colorimetric detec-tion. Cell viability was evaluated by cell count kit - 8. The expressions of UCP2 in transcription and translation levels were detected through transcription polymerase chain reaction and Western blot respectively. Results The levels of LDH,MDA,and intracellular ROS in LPS group significantly increased compared with control group[LDH:(829. 3 ± 75. 3)U/ L vs(223. 5 ± 23. 6)U/ L,MDA:(60. 90 ± 5. 73)nmol/ mgprot vs(19. 70 ± 1. 99)nmol/ mgprot,ROS:(410. 2 ± 81. 6)U/ well vs(94. 3 ± 18. 5)U/ well,all P ﹤ 0. 05)],while the cell viability and SOD activity significantly decreased[cell viability:0. 822 ± 0. 058 vs 1. 012 ± 0. 023,SOD:(49. 20 ± 5. 81)U/ mgprot vs(89. 80 ± 2. 57)U/ mg-prot,all P ﹤ 0. 05]. And the mRNA and protein expressions of UCP2 in LPS stimulation group were up - regulated (1. 867 ± 0. 130 vs 1. 028 ± 0. 097,0. 288 ± 0. 018 vs 0. 180 ± 0. 008,all P ﹤ 0. 05). 350 IU/ L and 700 IU/ L IN inter-vention significantly decreased the levels of LDH,MDA and intracellular ROS[LDH:(568. 2 ± 35. 7)U/ L,(622. 8 ± 27. 6)U/ L vs(829. 3 ± 75. 3)U/ L,MDA:(29. 20 ± 4. 20)nmol/ mgprot,(42. 10 ± 2. 32)nmol/ mgprot vs(60. 90 ± 5. 73)nmol/ mgprot,ROS:(270. 3 ± 46. 8)U/ well,(301. 5 ± 16. 9)U/ well vs(410. 2 ± 81. 6)U/ well,all P ﹤ 0. 05], increased the cell survival and the levels of SOD activity[cell viability:0. 960 ± 0. 029,0. 906 ± 0. 039 vs 0. 822 ± 0. 058,SOD:(75. 20 ± 2. 21)U/ mgprot,(61. 20 ± 3. 38)U/ mgprot vs(49. 20 ± 5. 81)U/ mgprot,all P ﹤ 0. 05]. And IN with 350 IU/ L and 700 IU/ L increased the mRNA and protein expression of UCP2(3. 830 ± 0. 265,2. 855 ± 0. 215 vs 1. 867 ± 0. 130,0. 464 ± 0. 215,0. 355 ± 0. 006 vs 0. 288 ± 0. 018,all P ﹤ 0. 05). Compared with 70 IU/ L and 700 IU/ L IN group,350 IU/ L IN group had better results. Conclusions IN attenuates LPS - induced oxidative injury in H9c2 cells,which is probably mediated through up - regulating the expression of UCP2.

ObjectiveTo study the change of the pulmonary surfactant protein C, D (SP-C, SP-D) and apoptosis of alveolar epithelium cells in neonatal rats with hyperoxia-induced lung injury.MethodsThe neonatal rats born within 24 hours were divided into the air group (n=50) and the hyperoxia group (n=50). The lung tissue was collected on the ifrst, third, seventh, tenth, fourteenth day after the hyperoxia exposure. The pathological changes were observed by HE staining. The apoptosis rate of lung epithelial cells was detected by TUNEL (terminal deoxyn ucleotidyl transfer-mediated end labeling). The content of SP-C and SP-D in broncho alveolar lavage lfuid (BALF) was detected by enzyme-linked immunosorbent assay.ResultsIn the air group, as age increased, the alveolar were gradually more completely formed with the regular shape and uniform size. Mean-while, in the hyperoxia group, as age increased, the number of alveolar was reduced, the small blood vessels expanded, the alve-olar hemorrhage was increased, the interstitial cells were increased and the lung tissue was swelling. The levels of SP-C, SP-D decreased with the increase of age in the air group. The level of SP-C in hyperoxia group was lower than that in the air group on the ifrst day. It was higher than that in the air group on the third day, peaked on the seventh day, and then it began to decline on the tenth day and decreased more obviously on the fourteenth day. The level of SP-D in hyperoxia group was not signiifcantly dif-ferent from that in the air group on the ifrst day, was higher than that in the air group on the third day and peaked on the seventh day. Then it began to decline on the tenth day and decreased more on the fourteenth day. ConclusionsLong-term inhalation of high concentrations of oxygen inhibits alveolar development. With the prolonged time of oxygen inhalation, the apoptosis of lung epithelial cells is increased, and the level of SP-C and SP-D in BALF was increased ifrst and then decreased.