Relationship between acute kidney injury before thoracic endovascular aneurysm repair and in-hospital outcomes in patients with type B acute aortic dissection

Objective Acute kidney injury （AKI） frequently occurs after catheter-based interventional procedures and increases mortality. However, the implications of AKI before thoracic endovascular aneurysm repair （TEVAR） of type B acute aortic dissection （AAD） remain unclear. This study evaluated the incidence, predictors, and in-hospital outcomes of AKI before TEVAR in patients with type B AAD. Methods Between 2009 and 2013, 76 patients were retrospectively evaluated who received TEVAR for type B AAD within 36 h from symptom onset. The patients were classified into no-AKI vs. AKI groups, and the severity of AKI was further staged according to kidney disease： im- proving global outcomes criteria before TEVAR. Results The incidence of preoperative AKI was 36.8%. In-hospital complications was significantly higher in patients with preoperative AKI compared with no-AKI （50.0% vs. 4.2%, respectively; P 〈 0.001）, including acute renal failure （21.4% vs. O, respectively; P 〈 0.001）, and they increased with severity of AKI （P 〈 0.001）. The maximum levels of body tem- perature and white blood cell count were significantly related to maximum serum creatinine level before TEVAR. Multivariate analysis showed that systolic blood pressure on admission （OR： 1.023; 95% CI： 1.003-1.044; P ： 0.0238） and bilateral renal artery involvement （OR： 19.076; 95% CI： 1.914 190.164; P = 0.0120） were strong predictors of preoperative AKI. Conclusions Preoperative AKI frequently occurred in patients with type B AAD, and correlated with higher in-hospital complications and enhanced inflammatory reaction. Systolic blood pressure on admission and bilateral renal artery involvement were major risk factors for AKI before TEVAR.

Veno-Venous Extracorporeal Membrane Oxygenation for Acute Lung Injury after Surgery for Aortic Dissection: A Case Report

Acute respiratory failure after surgery for aortic dissection is a serious complication that has been associated with increased mortality and morbidity. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is reported as one of the treatments for this life-threatening complication. A 78-year-old male patient was admitted to our hospital for Stanford type A acute aortic dissection. He underwent emergency replacement of the ascending aorta, after which he developed acute lung injury. It was difficult to maintain oxygenation with a respirator mask. Therefore, VV-ECMO was initiated on postoperative day 1. The oxygenation gradually improved, and VV-ECMO was continued until postoperative day 13. On postoperative day 25, mechanical ventilation was withdrawn. The patient was discharged from the hospital on postoperative day 149. We report a case of successful treatment of acute lung injury with VV-ECMO initiated after surgery for aortic dissection. VV-ECMO can be considered as a treatment option for severe acute lung injury after surgery for aortic dissection.

Acute lung injury and acute respiratory distress syndrome： experimental and clinical investigations

Acute lung injury （ALl） or acute respiratory distress syndrome （ARDS） can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALl or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Crotalaria ferruginea extract attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting MAPK/NF-κB signaling pathways

Objective:To evaluate the anti-inflammatory activity of Crotalaria ferruginea extract(CFE)and its mechanism.Methods:An intratracheal lipopolysaccharide(LPS)instillationinduced acute lung injury(ALI)model was used to study the antiinflammatory activity of CFE in vivo.The LPS-induced shock model was used to analyze the effect of CFE on survival.LPS-stimulated RAW264.7 cell model was used to investigate the anti-inflammatory activity of CFE in vitro and the effects on mitogen-activated protein kinase(MAPK)or nuclear factor-κB(NF-κB)signaling pathways.Results:CFE administration decreased the number of inflammatory cells,reduced the levels of tumor necrosis factor-α(TNF-α),monocyte chemotactic protein-1(MCP-1),interleukin-6(IL-6),and interferon-γ,and diminished protein content in the bronchoalveolar lavage fluid of mice.CFE also reduced lung wet-to-dry weight ratio,myeloperoxidase,and lung tissue pathological injury.CFE preadministration improved the survival rate of mice challenged with a lethal dose of LPS.CFE reduced LPS-activated RAW264.7 cells to produce nitric oxide,TNF-α,MCP-1,and IL-6.Furthermore,CFE inhibited nuclear translocation and phosphorylation of NF-κB P65,extracellular signal-regulated kinase,c-Jun N-terminal kinases,and P38 MAPKs.Conclusions:CFE exhibits potent anti-inflammatory activity in LPS-induced ALI mice,LPS-shock mice,and RAW264.7 cells,and its mechanism may be associated with the inhibition of NF-κB and MAPK signaling pathways.Crotalaria ferruginea may be a useful therapeutic drug for the treatment of ALI and other respiratory inflammations.

Predictors and in-hospital outcomes of preoperative acute kidney injury in patients with type A acute aortic dissection

Background Acute kidney injury （AKI） is common after surgery for acute aortic dissection （AAD） and increases in-hospital and long-term mortality. However, few data exist on the clinical and prognostic relevance of early preoperative AKI in patients with type A AAD We aimed to determine the incidence and predictors of preoperative AKI and the impact of AKI on in-hospital outcomes in patients with type A AAD. Methods From May 2009 to June 2014, we retrospectively enrolled 178 patients admitted to our hospital within 48 h from symp- tom onset and receiving open surgery for type A AAD. The patients were divided into no AKI and AKI groups and staged with AKI severity according to the KDIGO criteria before surgery. Results AKI occurred in 41 patients （23.0%）. The incidence of in-hospital complications was significantly higher in patients with preoperative AKI compared to no AKI （41.5% vs. 9.5%, P 〈 0.001）, including renal infarction （7.3% vs. 0, P = 0.012）, and it increased with AKI severity （Ptrend〈 0.001）. Patients with AKI had higher in-hospital mortality compared with pa- tients without AKI, although no significant difference was found （14.6% vs. 5.1%, P = 0.079）. Multivariate analysis indicated that male gender, diastolic blood pressure on admission and bilateral renal artery involvement were independent predictors of preoperative AKI in patients with type A AAD. Conclusions Early AKI before surgery was common in patients with type A AAD, and was associated with increased in-hospital complications. Male gender, diastolic blood pressure on admission and bilateral renal artery involvement were major predictors for preoperative AKI.

Leptin treatment ameliorates acute lung injury in rats with cerulein-induced acute pancreatitis

AIM:To determine the effect of exogenous leptin on acute lung injury (ALI) in cerulein-induced acute pancreatitis (AP). METHODS:Forty-eight rats were randomly divided into 3 groups. AP was induced by intraperitoneal (i.p.) injection of cerulein (50 μg/kg) four times,at 1 h intervals. The rats received a single i.p. injection of 10 μg/kg leptin (leptin group) or 2 mL saline (AP group) after cerulein injections. In the sham group,animals were given a single i.p. injection of 2 mL saline. Experimental samples were collected for biochemical and histological evaluations at 24 h and 48 h after the induction of AP or saline administration. Blood samples were obtained for the determination of amylase,lipase,tumor necrosis factor (TNF)-a,interleukin (IL)-1β,macrophage inflammatory peptide (MIP)-2 and soluble intercellular adhesion molecule (sICAM)-1 levels,while pancreatic and lung tissues were removed for myeloperoxidase (MPO) activity,nitric oxide (NOx) level,CD40 expression and histological evaluation. RESULTS:Cerulein injection caused severe AP,confirmed by an increase in serum amylase and lipase levels,histopathological findings of severe AP,and pancreatic MPO activity,compared to the values obtained in the sham group. In the leptin group,serum levels of MIP-2,sICMA-1,TNF-a,and IL-1b,pancreatic MPO activity,CD40 expression in pancreas and lung tissues,and NOx level in the lung tissue were lower compared to those in the AP group. Histologically,pancreatic and lungdamage was less severe following leptin administration. CONCLUSION:Exogenous leptin attenuates inflammatory changes,and reduces pro-inflammatory cytokines,nitric oxide levels,and CD40 expression in ceruleininduced AP and may be protective in AP associated ALI.

Moderate hypothermia attenuates lung in flammation inlipopolysaccharide- induced acute lung injury in rats

Objective To investigate the role of moderate h.vpothennia in the lung inflammation of rat acute lung injury induced by lipopolysaccharide(LPS). Methods A rat model of acute lung injury (ALl) was established by in-tin-tracheal instillation of lipopolysaccharide ( 1.5 mg/kg, 0.5 ml) at 16 h after LPS ( 1.0 mg/kg) intraperitoneal adrninis-tmtion. Thirty-four male Sprague Dawley rats were randomly divided into four groups: control group, receiving saline only;LPS group, receiving LPS; hypothennia group, treated with hypothennia without LPS; LPS + hypothennia group, treated with LPS and cooled to 32.5℃-33.0℃ as PaO2/FiO2. was below 300 mmHg. Hemodynamics and blood gases were record-ed every hour throughout the study. Rats were killed 4 h after ALl, and lung lavage was performed to measure the tumor ne-crosis factor α(TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) concentrations in bronchoalveolar lavage fluid (BALF) by using enzyme-linked immunosorbent assay (ELISA). Results PaO2/FiO2 was significantly decreased and PaCO2 was increased in the LPS group as compared to their baseline values( P＜0.01). Treatment with hypothermia inhib-ited the increase in PaCO2( P＜0.05) but had no effect on PaO2/FiO2 in the presence of LPS. The administration of LPS significantly increased the concentrations of TNF-α, IL-6 and IL-10 in BALF as compared to the control experiment( P＜0.05, P＜0.01 ). Moderate hypothermia reduced the expressions of TNF-α and IL-6 ( P＜0.01 ) but had no effect on the production of IL-10 ( P＞0.05). Conclusion Moderate hypothermia significantly inhibits proinflammatory cytokine ex-pressions in lipopolysaccharide-induced acute lung injury.

Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets

Background Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution （LPD） have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.Methods Oleic acid （0.1 ml/kg） was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups （n=5 each）： oleic acid-induced group （control group） with intravenous infusion of 12.5 ml/kg of lactated Ringer＇s solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD （12.5 ml/kg） 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.Results Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio,partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved （P＜0.05or 0.01）. Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group （P＜0.05）. Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group （P＜0.05）.Conclusions Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

Tanshinone ⅡA prevents acute lung injury by regulating macrophage polarization

Objective: Acute lung injury(ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone ⅡA(Tan-ⅡA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-ⅡA on ALI.Methods: A murine model of lipopolysaccharide(LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-ⅡA were investigated using in vivo and in vitro ALI models. Tan-ⅡA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-ⅡA function.Results: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-ⅡA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-ⅡA treatment. An in vitro assay also confirmed that including the Tan-ⅡA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-ⅡA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-ⅡA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization.Conclusion: This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-ⅡA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.

Protection of Total Flavonoid Fraction from Nervilia fordii on Lipopolysaccharide-induced Acute Lung Injury in Rats

Objective To investigate the effects of total flavonoid fraction(TFF) from Nervilia fordii on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats,and to explore their protective mechanism.Methods LPS-induced ALI model was established by LPS(5 mg/kg) injection via left cervical vein.Blood samples were collected from the cervical artery of all rats at 5 and 6 h after LPS challenge for arterial blood gas test and cytokines measurements,and pulmonary microvascular permeability(PMP),lung wet/dry weight ratio(W/D),and pathological features were observed.Results Phytochemical study showed that the TFF contained 67.3% of flavonoids expressed in rutin and three flavone glycosides.The TFF pretreatment(6.24 and 12.48 mg/kg) attenuated the partial arterial pressure of oxygen decline in blood significantly,and decreased the PMP and lung W/D in ALI rats.In addition,the TFF(6.24 and 12.48 mg/kg) also ameliorated the LPS-induced lung damages including alveolar edema,neutrophils infiltration,alveolar hemorrhage,and thickening of the alveolar wall.Furthermore,the treatment with the TFF(6.24 and 12.48 mg/kg) also down-regulated the levels of pro-inflammatory cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and intercellular adhesion molecule-1(ICAM-1),and up-regulated the level of anti-inflammatory cytokine IL-10 in serum of ALI rats simultaneously.Conclusion These results suggest that the TFF could protect LPS-induced ALI in rats,which may be mediated,at least in part,by adjusting the production of inflammatory cytokines including TNF-α,IL-6,ICAM-1,and IL-10.

C/EBP homologous protein deficiency aggravates acute pancreatitis and associated lung injury

AIM:To investigate the pathophysiological role of C/EBP homologous protein(CHOP)in severe acute pancreatitis and associated lung injury.METHODS:A severe acute pancreatitis model was induced with 6 injections of cerulein(Cn,50μg/kg)at 1-h intervals,then intraperitoneal injection of lipopolysaccharide(LPS,7.5 mg/kg)in CHOP-deficient(Chop-/-)mice and wild-type(WT)mice.Animals were sacrificed under anesthesia,3 h or 18 h after LPS injection.Serum amylase,lipase,and cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)-α],pathological changes,acute lung injury,and apoptosis in the pancreas were evaluated.Serum amylase and lipase activities were detected using a medical automatic chemical analyzer.Enzyme-linked immunosorbent assay kits were used to evaluate TNF-αand IL-6 levels in mouse serum and lung tissue homogenates.Apoptotic cells in sections of pancreatic tissues were determined by terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick-end labeling(TUNEL)analysis.The mouse carotid arteries were cannulated and arterial blood samples were collected for PaO2analysis.The oxygenation index was expressed as PaO2/FiO2.RESULTS:Administration of Cn and LPS for 9 and 24 h induced severe acute pancreatitis in Chop-/-and WT mice.When comparing Chop-/-mice and WT mice,we observed that CHOP-deficient mice had greater increases in serum TNF-α(214.40±19.52 pg/mL vs 150.40±16.70 pg/mL;P=0.037),amylase(4236.40±646.32U/L vs 2535.30±81.83 U/L;P=0.041),lipase(1678.20±170.57 U/L vs 1046.21±35.37 U/L;P=0.008),and IL-6(2054.44±293.81 pg/mL vs 1316.10±108.74pg/mL;P=0.046)than WT mice.The histopathological changes in the pancreases and lungs,decreased PaO2/FiO2ratio,and increased TNF-αand IL-6 levels in the lungs were greater in Chop-/-mice than in WT mice(pancreas:Chop-/-vs WT mice,hemorrhage,P=0.005;edema,P=0.005;inflammatory cells infiltration,P=0.005;total scores,P=0.006;lung:hemorrhage,P=0.017;edema,P=0.017;congestion,P=0.017;neutrophil infiltration,P=0.005,total scores,P=0.001;PaO2/FiO2ratio:393±17.65 vs 453.8,P=0.041;TNF-α:P=0.043;IL-6,P=0.040).Results from TUNEL analysis indicated increased acinar cell apoptosis in mice following the induction of acute pancreatitis.However,Chop-/-mice displayed significantly reduced pancreatic apoptosis compared with the WT mice(201.50±31.43vs 367.00±47.88,P=0.016).CONCLUSION:These results suggest that CHOP can exert protective effects against acute pancreatitis and limit the spread of inflammatory damage to the lungs.

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

Protective effect of Renqing Changjue on acute respiratory distress syndrome in rabbits

OBJECTIVE To investigate whether Renqing Changjue has a protective effect on acute respiratory distress syndrome(ARDS)induced by endotoxin lipopolysaccharide(LPS)in rabbits.METHODS Thirty-six healthy male New Zealand white rabbits were randomly divided into six groups:normal control group,model group,dexamethasone group,Renqing Changjue high,middle and low dose group,with six rabbits in each group.LPS was used to replicate the ARDS model after five consecutive days of gavage.Arterial pressure,respiratory rate and anal temperature blood were recorded for arterial blood gas analysis at 0,0.5,1,2 and 4 h,respectively.At the end of the four-hour experiment,rabbits were killed by bloodletting,and the lung tissue was quickly removed to determine the cytokines,SOD,MDA and pathological examination of rabbit lung.RESULTS Renqing Changjue can significantly reduce the pathological changes of lung in ARDS model group.The expression of AQP1 and MPO in rabbit lung was significantly decreased by immunohistochemistry(P<0.05),reduce the lung wet/dry weight ratio,increase the ratio of PaO_(2)/FiO_(2),inhibit the release of inflammatory factors and scavenge free radicals and antioxidant effects.CONCLUSION Renqing Changjue can effectively protect rabbits with acute respiratory distress syndrome induced by LPS,and may protect the lung by inhibiting the release of cytokines and anti-oxidation.

Research Progress of Traditional Chinese Medicine in the Treatment of Acute Respiratory Distress Syndrome

Based on the modern pathological research mechanism of ARDS,this paper summarizes the clinical therapeutic effect of traditional Chinese medicine on ARDS from the aspects of reducing inflammatory mediators,cells and factors,regulating signal pathway,regulating aquaporin,anticoagulation and so on.The purpose is to provide new theoretical basis and ideas for scholars in the future,and to improve the internationalization process of traditional Chinese medicine in the treatment of acute respiratory distress syndrome.

Hemorrhagic fever with renal syndrome complicated with aortic dissection:A case report

BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.

急性StanfordA型主动脉夹层术后中重度急性肾损伤、院内死亡及透析依赖的危险因素分析

目的:探究急性Stanford A型主动脉夹层术后发生中重度急性肾损伤(AKI)、院内死亡及透析依赖的危险因素。方法:回顾性连续纳入2014年12月至2016年12月在中国医学科学院阜外医院行升主动脉置换、全主动脉弓置换术联合支架象鼻手术、发病距就诊时间<14 d且资料完整的急性Stanford A型主动脉夹层患者294例。根据改善全球肾脏病预后组织(KDIGO)2012年标准进行AKI的诊断和分期,AKI 2或3期为中重度AKI,未发生AKI及AKI 1期为非中重度AKI。根据术后是否发生AKI及AKI的严重程度分为非中重度AKI组(n=186)和中重度AKI组(n=108)。采用多因素Logistic回归分析术后发生中重度AKI、院内死亡或出院时透析依赖的危险因素。结果:术后AKI 1期、AKI 2期、AKI 3期的发生率分别为42.2%(124/294)、15.3%(45/294)、21.4%(63/294),总AKI发生率为79.3%(232/294)。需肾脏替代治疗(CRRT)的患者比例为9.2%(27/294)。出院时透析依赖的患者比例为3.1%(9/294),院内死亡率为3.7%(11/294)。与非中重度AKI组相比,中重度AKI组合并高血压(79.6%vs.88.9%,P=0.040)、术前肾灌注减低的患者比例(7.0%vs.24.1%,P<0.001)均较高,术中体外循环时间[(161.6±34.0)min vs.(192.2±61.1)min,P<0.001]、主动脉阻断时间[(90.4±22.1)minvs.(104.3±29.5)min,P<0.001]均更长,术中超滤量更多[4000(3000,5000)mlvs.5000(4000,6262)ml,P<0.001]。多因素Logistic回归分析显示,术前肾灌注减低(OR=4.95,95%Cl:1.97~12.26,P<0.001)、体外循环时间延长(OR=1.01,95%Cl:1.00~1.02,P=0.016)为急性StanfordA型主动脉夹层术后发生中重度AKI的独立危险因素。进一步分析发现,体外循环时间延长(OR=1.02,95%Cl:1.01~1.03,P=0.007)和中重度AKI(OR=10.49,95%Cl:1.22~90.62,P=0.033)是院内死亡或出院时透析依赖的独立危险因素。结论:术前肾灌注减低、体外循环时间延长是急性Stanford A型主动脉夹层术后发生中重度急性肾损伤的独立危险因素。体外循环时间延长和中重度AKI明显增加院内死亡及出院时透析依赖的风险,因此,对此类患者需要进行密切关注随访。

基于网络药理学和动物实验探讨益肺解毒颗粒对急性肺损伤小鼠炎症反应及免疫功能的影响

目的:通过网络药理学和动物实验探讨益肺解毒颗粒对脂多糖(LPS)所致急性肺损伤(ALI)小鼠的影响及保护作用。方法:利用Swiss Target Prediction等平台,对药物的靶点进行筛选;利用Gene Cards数据库以“acute lung injury”为关键词整理疾病靶点;利用STRING平台进行蛋白互作分析,Cytoscape 3.7.2可视化交集靶点网络图并对核心靶点筛选;微生信平台进行KEGG通路富集和GO分析,Cytoscape 3.7.2构建成分-靶点-通路网络图。将30只C57小鼠随机分为空白组、模型组和低、中、高剂量组,模型及给药组采用LPS气管内滴注的方法建立ALI模型。记录小鼠体重变化;测定胸腺与脾脏指数;测定血清和肺泡灌洗液(BALF)中白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的含量;HE染色法观察肺组织病理变化。结果:筛选后获得药物靶点277个,成分与疾病的交集靶点146个,关键靶点有CASP3、EGFR、ESR1等,GO功能结果共1766个,KEGG富集结果有178条通路,PI3K-Akt信号通路为关键通路。相较空白组,模型组的胸腺与脾脏指数显著下降(均P<0.05);血清与BALF中IL-6、IL-1β、TNF-α含量显著增加(均P<0.05);肺组织明显出现炎性细胞浸润和出血。与模型组相比,给药组的胸腺指数显著增加(均P<0.05);高剂量组血清和BALF中炎症因子含量显著降低(均P<0.05)。结论:益肺解毒颗粒能改善因LPS所致的ALI小鼠肺组织病理损伤,其机制可能与增强免疫功能和抑制炎症因子分泌有关。

重组人白细胞介素35早期干预对脂多糖诱导大鼠急性肺损伤的保护作用研究

目的探讨重组人白细胞介素35(interleukin 35,IL-35)早期干预对脂多糖(lipopolysaccharide,LPS)诱导的大鼠急性肺损伤(acute lung injury,ALI)的保护作用。方法采用随机数字表法将40只雄性SD大鼠分成正常组、致伤组、对照组和治疗组,每组各10只(其中每个观察点5只)。正常组大鼠不作处理,其余3组大鼠麻醉后经暴露的气管滴注10 mg/kg LPS建立大鼠ALI模型。造模后,治疗组大鼠尾静脉注射重组人IL-352μg,每天给药1次,连续给药3天;对照组大鼠尾静脉注射同等剂量无菌生理盐水,每天1次,连续3天;正常组和致伤组大鼠不进行药物干预。观察各组大鼠干预后第1、3天肺组织病理学变化及评分、动脉血氧分压(arterial partial pressure of oxygen,PaO_(2))和二氧化碳分压(partial pressure of carbon dioxide,PCO_(2))变化。采用酶联免疫吸附分析(enzyme-linked immunosorbent assay,ELISA)法检测大鼠肺组织匀浆上清液中肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)和白细胞介素10(interleukin 10,IL-10)含量。结果与正常组比较,致伤组、对照组和治疗组大鼠建模后第1天的肺组织病理评分均显著升高、PaO_(2)显著降低(P均<0.05);治疗组大鼠第3天肺组织病理评分显著低于致伤组和对照组、PaO_(2)显著高于致伤组和对照组,致伤组、对照组和治疗组大鼠第3天PCO_(2)较正常组显著升高(P均<0.05)。与正常组相比,致伤组、对照组和治疗组大鼠第1、3天TNF-α、IL-10含量明显升高(P均<0.05);治疗组大鼠第1、3天TNF-α含量明显低于对照组(P均<0.05),第1天IL-10含量明显低于致伤组和对照组,但第3天IL-10含量明显高于致伤组和对照组(P均<0.05)。结论重组人IL-35具有减轻LPS致大鼠肺损伤的作用,可降低肺损伤组织TNF-α水平,提高IL-10水平的作用。

Preventive effects of sevoflurane treatment on lung inflammation in rats

Objective:To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopolysaccharide-induced acute lung injury(ALI).Methods:The rat model of ALI was established by intratracheal instillation of lipopolysaccharide(LPS).45 infantile SD rats[body weight(272±15) g]were randomly divided into 3 groups(n=15):control group,LPS group, sevoflurane group.NS(1 mL/kg) was instillated in rats’airways of control group;LPS(5 mg/ kg) was instillated in rats’airways of LPS group.Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats’airways.Six hours after NS or LPS instillation,all rats were exsanguinated.Lung tissues were examined by HE staining.Expressions of TNF-αand ICAM1 mRNA were detected by semiquantitative RT-PCR techniques.The protein level of TNF-αand ICAM1 were assessed by western blot techniques.Results:In LPS group the permeability of lung tissues increased,organizational structure severely damaged and the alveolar wall turned thick,with interstitial edema and Europhiles infiltrated increasingly.The LPS group had higher mRNA expressions of TNF-αand ICAM1 than control group and sevoflurane group (P【0.05),and LPS group had higher protein level of TNF-αand ICAMI than control group and sevoflurane group(P【0.05).Conclusions:Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.

避瘟解毒颗粒对LPS诱导急性肺损伤小鼠保护作用的研究

探究避瘟解毒颗粒对脂多糖(LPS)致急性肺损伤(ALI)小鼠的保护作用。将30只C57小鼠随机分为正常组、模型组、地塞米松组、避瘟解毒颗粒高、低剂量组,每组6只,每天给药1次,连续给药7 d。模型组、地塞米松组、避瘟解毒颗粒给药组气管滴注脂多糖(LPS)构建小鼠急性肺损伤模型(ALI)。造模后72 h取材检测,分析小鼠体重变化情况;血常规指标;胸腺指数;ELISA法检测肺泡灌洗液(BALF)中IL-1β、IL-6、TNF-α水平;HE染色法观察肺组织病理变化。与模型组比较,避瘟解毒颗粒高剂量组小鼠血清中血常规指标,BALF中炎性细胞因子IL-6、TNF-α含量,肺组织损伤程度均有不同程度的降低(P<0.05,P<0.01),且高剂量组能显著升高ALI小鼠的胸腺指数(P<0.01)。避瘟解毒颗粒对LPS诱导急性肺损伤发挥一定的保护作用,改善小鼠肺组织的病理改变,增强免疫功能,其作用机制可能与抑制促炎细胞因子的分泌及发挥抗炎作用有关。