Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia

Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.

Host Factors Alter Effects of Angiopoietin-Like Protein 8 on Glucose Homeostasis in Diabetic Mice

Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013. Subsequent studies of human ANGPTL8 for short term (3 to 8 days) in non-diabetic mice showed little or no increase in beta cell proliferation. Here, we examined the effect of ANGPTL8 on glucose homeostasis in models that have not been examined previously. We expressed mouse ANGPTL8 using adenovirus in 2 mouse models of diabetes (streptozotocin and Non-Obese Diabetic (NOD) mice) over 2 weeks. Also, we tested ANGPTL8 in NOD mice deficient in leukocyte 12-lipoxygenase (12LO), an enzyme that contributes to insulitis and loss of beta cell function in NOD, in an effort to determine whether 12LO deficiency alters the response to ANGPTL8. Adenovirus-mediated expression of ANGPTL8 lowered blood glucose levels in streptozotocin treated mice without an increase in beta cell proliferation or serum insulin concentration. While ANGPTL8 did not reverse hyperglycemia in overtly hyperglycemic NOD mice or alter glucose homeostasis of non-diabetic NOD mice, ANGPTL8 reduced blood glucose levels in 12LOKO NOD mice. However, the lower glucose levels in 12LOKO NOD were not associated with higher serum insulin levels or beta cell proliferation. In summary, while mouse ANGPTL8 does not increase beta cell proliferation in NOD mice or streptozotocin treated mice in agreement with studies in non-diabetic mice, it lowers blood glucose levels in multiple low-dose streptozotocin induced diabetes and 12LO deficiency indicating that host factors influence the impact of ANGPTL8 on glucose homeostasis.

Association between Maternal Serum Concentrations of Angiopoietin-like Protein 2 in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus

Background：A recent study reported a positive association between elevated serum levels of angiopoietin-like protein 2 （ANGPTL2） and the development of type 2 diabetes in a general population.However,the relationship of serum ANGPTL2 levels with the risk of developing gestational diabetes mellitus （GDM） has not been reported to date.The aim of this study was to investigate the change of maternal serum ANGPTL2 concentrations in the first trimester of pregnancy and to determine whether ANGPTL2 is a biomarker for subsequent GDM development.Methods：We conducted a prospective,nested case-control study in a pregnancy cohort.First-trimester ANGPTL2 levels were measured using a high-resolution assay in 89 women who subsequently developed GDM and in a random sample of 177 women who remained euglycemic throughout the pregnancy.Median ANGPTL2 levels were compared using Mann-Whitney U-test.Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among ANGPTL2 quartiles.Results：The serum levels of ANGPTL2 was higher in women with GDM than that in women without GDM （3.06 [2.59,3.65] ng/ml vs.2.46 [2.05,2.96] ng/ml,P =0.003）.Fasting blood glucose was higher in women with GDM than that in women without GDM （5.0 ± 0.9 mmol/L vs.4.4 ± 0.6 mmol/L,P 〈 0.001）.Glucose challenge test showed that the blood glucose was higher in women with GDM than that in women without GDM （9.1 ± 3.5 mmol/L vs.6.2 ± 1.2 mmol/L,P 〈 0.001）.A multivariate model adjusted for baseline characteristics,medical complications,and gestational characteristics revealed that the risk of developing GDM among women in Q4 compared with Q1 was 2.90-fold more likely to develop GDM later in pregnancy.Conclusions：At 1 1-13 weeks in pregnancies that develop GDM,the serum concentration of ANGPTL2 is increased,and it can be combined with maternal factors to provide effective early screening for GDM.

外周血TG/Cys-C、脂联素、VILIP-1水平对2型糖尿病合并急性缺血性脑卒中患者预后的预测价值

目的探究外周血三酰甘油(TG)/胱抑素(Cys-C)、脂联素、视锥样蛋白1(VILIP-1)水平对2型糖尿病(T2DM)合并急性缺血性脑卒中(AIS)患者预后的预测价值。方法选取运城市中心医院2020年7月至2023年7月收治的136例T2DM合并AIS患者为研究对象,根据患者的随访3个月的改良Rankin量表(mRS)评分将≤2分者分为良好组(n=84),>2分者分为不良组(n=52)。比较两组的一般资料和外周血TG/Cys-C、脂联素、VILIP-1水平,采用多因素logistic回归分析影响T2DM合并AIS患者预后的因素,并通过受试者工作特征曲线(ROC)曲线评估外周血TG/Cys-C、脂联素、VILIP-1水平对T2DM合并AIS患者预后的预测价值。结果两组的年龄、NIHSS评分、TG/Cys-C、脂联素、VILIP-1水平进行比较,差异均有统计学意义(P<0.05)。多因素logistic回归分析结果显示年龄、NIHSS评分、TG/Cys-C、脂联素、VILIP-1水平均为影响T2DM合并AIS患者预后的独立因素(P<0.05)。ROC曲线结果显示,外周血TG/Cys-C、脂联素、VILIP-1及三者联合预测T2DM合并AIS患者预后情况的AUC面积分别为0.710、0.725、0.679、0.804,表明外周血TG/Cys-C、脂联素、VILIP-1水平对T2DM合并AIS患者的预后均具有一定的预测价值,且三者联合的效果最佳,灵敏度为90.5%,特异度为75.0%(P<0.05)。结论T2DM合并AIS患者的预后不良情况与年龄、NIHSS评分、TG/Cys-C、脂联素、VILIP-1水平有关,外周血TG/Cys-C、脂联素、VILIP-1水平对T2DM合并AIS患者的预后均具有一定的预测价值,且三者联合预测的效果最高。

活血消痛方对胫腓骨骨折患者血清FGF-2、IGF-1、sICAM-1、CD4~+/CD8~+的影响

目的:观察活血消痛方治疗胫腓骨骨折的临床疗效及其对患者血清成纤维细胞生长因子-2(fibroblast growth factor-2,FGF-2)、胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)、可溶性细胞间黏附分子-1(soluble intercellular adhesion molecule-1,sICAM-1)、CD4^(+)/CD8^(+)的影响。方法:将92例胫腓骨骨折患者按照随机数字表法分为对照组和试验组,每组各46例。对照组术后给予常规治疗方案,试验组在对照组的基础上给予活血消痛方治疗。比较两组患者的临床疗效及治疗前后视觉模拟评分(visual analogue score,VAS)变化情况,检测两组患者治疗前后血清FGF-2、IGF-1、sICAM-1、CD4^(+)/CD8^(+)。结果:试验组有效率为91.30%,对照组有效率为71.74%,两组患者有效率比较,差异具有统计学意义(P<0.05)。两组患者治疗后VAS评分低于本组治疗前,且试验组治疗后VAS评分低于对照组治疗后,差异具有统计学意义(P<0.05)。两组胫腓骨骨折患者治疗后血清FGF-2、IGF-1、sICAM-1、CD4^(+)/CD8^(+)低于本组治疗前,且试验组治疗后低于对照组治疗后,差异具有统计学意义(P<0.05)。结论:活血消痛方治疗胫腓骨骨折患者,可有效缓解患者疼痛,改善血清指标。

ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior

AIM To explore expression of angiopoietin-like protein 2(ANGpT L2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer. METHODS Western blotting was used to detect expression of ANGp TL2 in 60 human normal gastric tissues, 60 human gastric cancer tissues and gastric cell lines including GES-1, N87, SGC7901, BGC823 and pA MC82. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and Transwell assay were used to detect the proliferation and invasive ability of gastric cancer cells. RESULTS Compared to normal tissues, ANGp TL2 protein levels were significantly upregulated in gastric tissues, and this level was closely correlated with gastric tumor grade, clinical stage and lymph node metastasis. Compared to GES-1 cells, ANGpT L2 mR NA and protein levels were significantly increased in gastric cancer cells including N87, SGC7901, BGC823 and p AMC82. The expression of ANGpT L2 in highly malignant gastric cancer cell lines BGC823 and pA MC82 was significantly higher than in low malignancy gastric cancer cell lines N87 and SGC7901. MTT and Transwell experiments indicated that the proliferation rate and invasive ability of stable overexpressed gastric cancer cells was faster than in cells transfected with Lv-NC and blank controlcells, and the invasive ability of stable overexpressed gastric cancer cells was higher than that of cells transfected with Lv-NC and blank control cells.CONCLUSION ANGp TL2 contributed to proliferation and invasion of gastric cancer cells. In clinical treatment, ANGpT L2 may become a new target for treatment of gastric cancer.

Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease

Angiopoietin-like protein 2(ANGPTL2)stimulates inflammation and is important in the pathogenesis of diabetic kidney disease(DKD).Irbesartan is helpful in reducing diabetes-induced renal damage.In this study,the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined.Wistar rats were divided into normal,DKD,and DKD+irbesartan groups.The DKD+irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage.The 24-h urinary albumin was determined each week,renal pathological changes were observed,and expression of ANGPTL2 and nuclear factor-kappa B(NF-κB)in rat renal tissue was assessed by immunohistochemistry.Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations(0,25,50,and 75ºg/mL).Expression of ANGPTL2 and phosphorylated IκB-αwas assessed by Western blotting.The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1(MCP-1)were assessed by real-time polymerase chain reaction.The DKD rats displayed proteinuria,podocyte injury,and increased ANGPTL2 and NF-κB expression.All were relieved by irbesartan treatment.In podocytes cultured in elevated glucose,ANGPTL2 and phosphorylated IκB-αwere overexpressed at the protein level,and ANGPTL2 and MCP-1 were highly expressed at the mRNA level.Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level.The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.

Leukocyte immunoglobulin-like receptor B2 overexpression as a promising therapeutic target and noninvasive screening biomarker for colorectal cancer

BACKGROUND Colorectal cancer(CRC)has become the second most deadly malignancy in the world,and the exploration of screening markers and precise therapeutic targets is urgent.Our previous research identified leukocyte immunoglobulin-like receptor B2(LILRB2)protein as a characteristic protein of CRC,but the association between LILRB2 expression and clinicopathological features,the internal mechanism related to CRC progression,and screening diagnostic efficacy are not clear.Therefore,we hypothesized that LILRB2 is significantly highly expressed in CRC tissues,correlated with advanced stage and a poor prognosis,and could be used as a therapeutic target and potential screening biomarker for CRC.AIM To explore whether LILRB2 can be used as a potential therapeutic target and noninvasive screening biomarker for CRC.METHODS Patients who underwent radical surgery for CRC at China-Japan Friendship Hospital between February 2021 and October 2022 were included.Cancer and paracancerous tissues were collected to verify LILRB2 expression,and the association between LILRB2 expression and clinicopathological features was analysed.Serum was collected from CRC patients,adenoma patients and healthy controls during the same period to assess the diagnostic value of LILRB2 as a noninvasive screening biomarker,and its diagnostic value was further compared with that of the traditional markers carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9).RESULTS A total of 58 CRC patients were included,and LILRB2 protein was significantly overexpressed in cancer tissues compared with paracancerous tissues(P<0.001).Angiopoietin-like protein 2(ANGPTL2)protein,as the ligand of LILRB2,was synergistically overexpressed in CRC tissues(P<0.001),and overexpression of LILRB2 and ANGPTL2 protein was significantly correlated with poor to moderate differentiation,vascular involvement,lymph node metastasis,distant metastasis,advanced tumor-node-metastasis stage and a poor prognosis(P<0.05),which suggested that LILRB2 and ANGPTL2 are closely associated with CRC progression.In addition,serum LILRB2 concentrations increased stepwise in healthy individuals,adenoma patients and CRC patients with statistically significant differences.The sensitivity of serum LILRB2 for the diagnosis of CRC was 89.74%,the specificity was 88.89%,the area under the curve was 0.95,and the diagnostic efficacy was better than that of conventional CEA and CA19-9.CONCLUSION LILRB2 protein can be used as a potential novel therapeutic target and noninvasive screening biomarker for CRC,which is beneficial for early screening and precise treatment.

Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer

Background:Lymph node metastasis(LNM)is the primary mode of metastasis in gastric cancer(GC).However,the precise mechanisms underlying this process remain elusive.Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis,yet the role of lipoprotein lipase(LPL),a pivotal enzyme involved in exogenous lipid uptake,remains uncertain in tumor metastasis.Therefore,the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process.Methods:Intracellular lipid levels were quantified using oil red O staining,BODIPY 493/503 staining,and flow cytometry.Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown.Protein expression levels were assessed through immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assays.The mouse popliteal LNM model was utilized to investigate differences in LNM.Immunoprecipitation and mass spectrometry were employed to examine protein associations.In vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4(ANGPTL4)phosphorylation.Results:We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive(N+)GC and further demonstrated that a high-fat diet can expedite LNM.LPL was found to be significantly overexpressed in N+GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells.Leptin,an obesity-related hormone,intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage.Circulating leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1(IRE1)kinase,leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL.Moreover,our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid,which then triggered the cyclooxygenase-2/prostaglandin E2(PGE2)pathway,thereby promoting tumor lymphangiogenesis.Conclusions:Leptin-induced phosphorylation of ANGPTL4 facilitates LPLmediated lipid uptake and consequently stimulates the production of PGE2,ultimately facilitating LNM in GC.

2型糖尿病患者血清APPL1与尿白蛋白排泄率的相关性研究

目的研究2型糖尿病患者血清磷酸酪氨酸衔接蛋白1（APPL1）水平变化与尿白蛋白排泄率的关系，探讨APPL1在糖尿病肾病（DKD）发生发展中的意义。方法将288例初治2型糖尿病患者，根据尿白蛋白/肌酐比率（UACR）分为正常白蛋白尿组（UACR〈30 mg/g, n=116）、微量白蛋白尿组（UACR 30-300 mg/g, n=95）、大量白蛋白尿组（UACR〉300 mg/g, n=77），选取性别及年龄匹配健康体检者130名作为对照组，采用ELISA法测定血清APPL1、肿瘤坏死因子α（TNF-α）及脂联素水平。结果2型糖尿病患者血清APPL1含量较对照组显著升高（P〈0.01），且随UACR的升高而升高。2型糖尿病患者血清APPL1与估算的肾小球滤过率呈显著负相关（r=－0.246, P〈0.01），与HbA1C、低密度脂蛋白胆固醇、总胆固醇、三酰甘油、胰岛素抵抗指数、血肌酐、血尿素氮、收缩压、TNF-α、脂联素呈显著正相关（r=0.119、0.167、0.209、0.194、0.273、0.242、0.131、0.144、0.365、0.952, P〈0.05或P〈0.01）。结论2型糖尿病患者血清APPL1水平显著升高，且随着UACR的升高而升高，提示其可能参与DKD的发生发展。

Up-regulation of indoleamine 2,3-dioxygenase 1(IDO1)expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (Trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penilesquamous cell carcinoma (PSCC) and explored their clinical significance.Methods: IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn)were examined in 114 PSCC patients by immunohistonchemistry and solid-phaseextraction-liquid chromatography-tandem mass spectrometry. The survival was analyzed using Kaplan-Meier method and the log-rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were definedby principal component analysis. The correlativity was assessed by Pearson’s correlation analysis.Results: The expression level of IDO1 in PSCC cells was positively correlatedwith serum Kyn concentration and Kyn/Trp radio (KTR;both P < 0.001) but negatively correlated with serum Trp concentration (P = 0.001). Additionally, IDO1 upregulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P < 0.001) and high pathologic grade (P = 0.008and 0.032, respectively). High expression level of IDO1 in cancer cells and serumKTR were associated with short disease-specific survival (both P < 0.001). However, besides N stage (hazard radio [HR], 6.926;95% confidence interval [CI],2.458-19.068;P < 0.001) and pathologic grade (HR, 2.194;95% CI, 1.021-4.529;P = 0.038), only serum KTR (HR, 2.780;95% CI, 1.066-7.215;P = 0.036) was anindependent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon-𝛾 (IFN𝛾, P < 0.001) and immunosuppressivemarkers (programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 and 2;all P < 0.05), and the infiltration ofimmune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumorassociated macrophages, and myeloid-derived suppressor cells;all P < 0.001) inPSCC tissues. Furthermore, the expression of IDO1 was induced by IFN𝛾 in a dosedependent manner in PSCC cells.Conclusions: IFN𝛾-induced IDO1 plays a crucial role in immunoediting andimmunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1catabolic activity, can be utilized as an independent prognostic factor for PSCC.

血清Angptl2/Angptl1比值与短暂性脑缺血发作后脑梗死发生风险的关系

目的探讨血清血管生成素样蛋白2/血管生成素样蛋白1(Angptl2/Angptl1)比值与短暂性脑缺血发作后脑梗死发生风险的关系。方法选取2019年7月-2020年7月鹤壁市人民医院收治的265例短暂性脑缺血发作患者为研究对象,根据7 d内有无发生脑梗死将其分为脑梗死组(n=87)和无脑梗死组(n=178)。采用酶联免疫吸附(ELISA)法检测血清Angptl2、Angptl1水平,并计算Angptl2/Angptl1比值,采用牛津郡卒中工程ABCD2、ABCD3-I评分、Essen卒中风险评分(ESRS)、卒中预测工具-II(SPI-II)4种评分方法对患者行脑梗死风险预测。结果脑梗死组Angptl2水平、Angptl2/Angptl1比值、ABCD2、ABCD3-I、ESRS、SPI-II及症状持续时间≥60 min、弥散加权成像(DWI)高信号、糖尿病比例高于无脑梗死组,Angptl1水平低于无脑梗死组,差异均有统计学意义(P均<0.05)。短暂性脑缺血发作后脑梗死患者血清Angptl2/Angptl1比值与ABCD2、ABCD3-I、ESRS、SPI-II成正相关(r=0.507、0.512、0.496、0.498,P均<0.05)。Angptl2/Angptl1比值、ABCD2、ABCD3-I、ESRS、SPI-II预测短暂性脑缺血发作后脑梗死的曲线下面积(AUC)分别为0.884、0.769、0.708、0.835、0.844,其中Angptl2/Angptl1比值预测AUC高于ABCD2、ABCD3-I,差异均有统计学意义(Z=3.212、4.404,P均<0.05)。结论血清Angptl2/Angptl1比值在预测短暂性脑缺血发作患者发生脑梗死中有重要价值。

氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤的影响

目的 探讨氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤（acute lung injury, ALI）的影响。方法 成年雄性SD大鼠100只，体重280 g ~ 320 g，采用计算机简单随机分组法随机分为5组（每组20只）：对照组（C组）、内毒素组（L组）、氯胺酮组（K组）、乌斯他丁组（U组）、氯胺酮复合乌斯他丁组（K＋U组）。除C组外，其余大鼠腹腔注射0.03 %脂多糖（lipopolysaccharide, LPS）1 mg/kg，注射后16 h时，由尾静脉再次注射0.l % LPS 1.5 mg/kg，建立大鼠ALI 模型。U组、K＋U组分别在第2次注射LPS后经尾静脉注射乌司他丁 50 000 U/kg，注射乌司他丁后即刻，K 组、K＋U 组经尾静脉以微量泵持续输注氯胺酮 10 ㎎？㎏-1？h-1，其余组注射等容量生理盐水。于第2次注射 LPS 后1、2、3、4 h （T1~4）时，各组取5只大鼠，抽取腹主动脉血样0.5 ml，测定氧分压（PaO2），抽取下腔静脉血样2 ml，测定血清肿瘤坏死因子（tumor necrosis factor，TNF）-α和白介素（interleukin，IL）-6浓度；放血处死大鼠，取右肺上叶组织，光镜下观察肺组织病理学结果，进行肺组织病理半定量评分及测定核因子（nuclear factor-κB, NF-κB）抑制蛋白α （inhibitor of nuclear factor-κBα, IκBα）表达；取右肺中叶组织100 mg测定肺组织NF-κB活性；取右肺下叶组织，计算肺湿干重比（W/D）。结果 与C组比较，L组、K组、U组和K＋U组PaO2降低，血清TNF-α、IL-6浓度和肺组织NF-κB活性升高，IκBα表达降低， W/D升高（P〈0.01）；与L组比较，K组、U组和K＋U组PaO2升高，血清TNF-α、IL-6浓度和肺组织NF-κB活性降低，IκBα表达升高，W/D降低，肺组织病理评分降低 （P〈0.05或0.01）；与K组和U组比较，K＋U组各时点PaO2升高，血清TNF-α、IL-6浓度和肺组织NF-κB活性（2.49±0.23）降低，IκBα表达（35.1±3.4）升高，W/D（4.91±0.16）降低，肺组织病理评分（7.8±0.8）降低（P〈0.05或0.01） 。结论 氯胺酮复合乌司他丁可减轻大鼠ALI，较两者单独应用效果显著。