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.

Impact of Toll-like Receptor 4 Deficiency on Cerebrocardiac Syndrome

In order to investigate the role of Toll-like receptor 4 （TLR4） in cerebrocardiac syndrome （CCS）, the partial cerebral ischemia/reperfusion （I/R） models in mice with different TLR4 genotypes were established in the present study. TLR4 wild-type （C3H/HeN） and mutant （C3H/HeJ） mice of 6-8 weeks of age were divided into 4 groups at random： C3H/HeN sham group （n=10）, C3H/HeJ sham group （n=10）, C3H/HeN model group （n=10） and C3H/HeJ model group （n=10）. Partial cerebral I/R was caused by the middle cerebral artery occlusion （MCAO） to duplicate CCS models in mice. After the operation, the electrocardiogram （ECG）, the level of tumor necrosis factor-alpha （TNF-c0 in myocardial tissue and the cardiac pathological changes were observed in each group. It was shown that the brain infarct volume in C3H/HeN model group was larger than that in C3H/HeJ model group （P〈0.01）. The ST segment change and T wave inversion occurred frequently in model groups. Moreover, the TNF-ct level in C3H/HeN model group was higher than that in C3H/HeJ model group （P〈0.01）. The myocar- dial injury was aggravated in C3H/HeN group as compared with C3H/HeJ group. It was concluded that TLR4 was implicated in the development of CCS.

Yemazhui(Herba Eupatorii Lindleyani)ameliorates lipopolysaccharide-induced acute lung injury via modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flor

OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in vivo.METHODS:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry method.Then,HEL was found to suppress LPS-induced ALI in vivo.Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)groups.The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model.Leukocyte counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and immunofluorescence.Besides,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal contents.RESULTS:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance.Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung tissue.In addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturbance.CONCLUSIONS:In summary,our findings revealed that HEL has a protective effect on LPS-induced ALI in rats,and its mechanism may be related to inhibiting TLR4/NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.

The implication of dendritic cells in lung diseases:Immunological role of toll-like receptor 4

The immune responses play a profound role in the progression of lung lesions in both infectious and non-infectious diseases.Dendritic cells,as the"frontline"immune cells responsible for antigen presentation,set up a bridge between innate and adaptive immunity in the course of these diseases.Among the receptors equipped in dendritic cells,Toll-like re-ceptors are a group of specialized receptors as one type of pattern recognition receptors,capable of sensing environmental signals including invading pathogens and self-antigens.Toll-like receptor 4,a pivotal member of the Toll-like receptor family,was formerly recognized as a receptor sensitive to the outer membrane component lipopolysaccharide derived from Gram-negative bacteria,triggering the subsequent response.Moreover,its other essential roles in immune responses have drawn significant attention in the past decade.A better under-standing of the implication of Toll-like receptor 4 in dendritic cells could contribute to the management of pulmonary diseases including pneumonia,pulmonary tuberculosis,asthma,acutelung injury,and lung cancer.

Relationship between the expression of Toll-like receptor 2 and 4 in mononuclear cells and postoperative acute lung injury in orthotopic liver transplantation

Background The aim of this study was to investigate the potential relationship between the dynamic expression of Toll-like receptor 2 and 4 （TLR2/4） in peripheral blood mononuclear cells as well as changes in serum concentration of inflammatory factors and acute lung injury （ALl） in patients after orthotopic liver transplantation （OLT）. Methods The peripheral blood samples of 27 patients （23 men and 4 women with ASA Ⅲ to Ⅳ） who received OLT were collected for measurement of TLR2/4 at T1 （after induction of anesthesia）, T2 （25 minutes after anhepatic phase）, T3 （3 hours after graft reperfusion） and T4 （24 hours after graft reperfusion）. The expression of TLR2/4 in mononuclear cells was measured by flow cytometry. The serum concentrations of tumor necrosis factor （TNF）-α, interleukin （IL）-1β and IL-8 were measured by enzyme-linked immunosorbent assay （ELISA）. Twenty-seven patients were assigned to ALl group （n=-9） and non-ALl group （n=-18） according to the diagnostic criteria of ALl. The expression of TLR2/4 in the ALl group or non-ALl group was analyzed. Results Compared to the non-ALl group, the volumes of blood loss, ascites, total output and transfused red blood cells were higher in the ALl group, and the anhepatic phase lasted longer （P 〈0.05, P 〈0.01）. The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4, and serum concentrations of TNF-α, IL-1β and IL-8 increased significantly too. There was no significant difference in Child-Turcotte-Pugh （CTP） scores between the ALl group and non-ALl group （P 〉0.05）. The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4 in the ALl group （P 〈0.05, P〈0.01）. A positive correlation was noted between the expression of TLR4 in mononuclear cells and the serum concentrations of TNF-α, IL-1β （P=0.041, P=0.046） in the ALl group. In the non-ALl group, statistical results showed that the expression level of TLR2/4 in mononuclear cells was not significantly different during the peri-operative period of OLT （besides TLR4 expression at T4）. Compared to expression in mononuclear cells was more significant in the mononuclear cells exceeded that at T1 by one time were more 16. the non-ALl group, the increasing amplitude of TLR2/4 ALl group. The patients whose TLR2/4 expression in likely to suffer from ALl （P=0.013）, with a relative risk of Conclusion The expression level of TLR2/4 in mononuclear cells increases significantly in the peri-operative period of OLT, and it may be a high risk factor for occurrence of postoperative ALl.

TLR2和TLR4在大鼠光滑念珠菌肺部感染中的表达及意义

目的研究Toll样受体2(TLR2)和TLR4在光滑念珠菌肺部感染大鼠中的作用。方法将36只大鼠分为3组,每组12只:对照组(A组)、未免疫抑制肺部光滑念珠菌感染组(B组)及免疫抑制肺部光滑念珠菌感染组(C组)。每组分别在造模成功后第1、3天各处死大鼠6只,观察肺组织病理变化,用逆转录PCR(RT-PCR)法检测肺组织TLR2、TLR4mRNA的表达、酶联免疫吸附实验(ELISA)法测定TNF-α蛋白水平。结果 A组肺组织正常;B组部分肺泡塌陷、炎症细胞浸润,未见孢子或菌丝;C组大部分肺泡塌陷,部分扩张,大量炎症细胞浸润、并有孢子菌丝聚积。第1、3天TLR2mRNA和TNF-α蛋白表达水平C组明显高于其他两组(P<0.01),B组高于A组(P<0.05);C组第3天TLR2、TLR4mRNA,TNF-α表达水平高于第1天(P<0.05,P<0.01),且TLR4表达高于A组(P<0.05)。结论 TLR2和TNF-α可能参与光滑念珠菌肺部感染的发生发展,TLR4可能起协同作用。

CCR4在T_1期肺腺癌组织中的表达及其临床意义

目的探讨T1期肺腺癌肿瘤浸润淋巴细胞(TILs)中趋化因子受体4(CCR4)的表达及临床意义。方法采用组织芯片技术和免疫组织化学技术测定185例T1期肺腺癌TILs中CCR4的表达情况,分析CCR4表达与临床病理特征及预后的关系。结果 CCR4表达于TILs的胞浆,阳性表达率为(17.8±7.3)%,并以17.8%为界值分为低表达组和高表达组。CCR4阳性表达率与年龄、性别、吸烟史无关(P>0.05),与T分期、淋巴结转移、脉管浸润和复发有关(P<0.05)。CCR4低表达组与高表达组患者的3年生存率分别为98.7%和88.1%,5年生存率分别为89.8%、88.1%,8年生存率分别为86.6%、51.6%,差异有统计学意义(P<0.05);CCR4低表达组与高表达组患者的3年无复发生存率分别为93.3%、82.3%,5年无复发生存率分别为86.4%、74.5%,8年无复发生存率分别为83.4%、50.5%,差异有统计学意义(P<0.05)。结论 CCR4在T1期肺腺癌TILs中的高表达与肺腺癌侵袭性增强及淋巴结转移有关,有望成为预测肺腺癌预后和靶向治疗的指标。

Intravenous infusion of mesenteric lymph from severe intraperitoneal infection rats causes lung injury in healthy rats

AIM: To investigate whether mesenteric lymph from rats with severe intraperitoneal infection (SII) induces lung injury in healthy rats.

苗药杆努尽烟对慢性支气管炎大鼠肺组织TLR4及TNF-α表达的影响

目的:研究苗药杆努尽烟对慢性支气管炎模型大鼠肺组织Toll样受体4(TLR4)及肿瘤坏死因子-α(TNF-α)水平的影响。方法:50只SD大鼠分为正常对照组、慢性支气管炎模型组、杆努尽烟低剂量组(2 g/kg)、杆努尽烟高剂量组(8 g/kg)及桂龙咳喘宁阳性药物组,除正常对照组外,其余各组通过烟熏加脂多糖气管注射法建立慢性支气管炎大鼠模型;观察各组大鼠呼吸系统症状及肺组织病理变化,ELISA法检测各组大鼠肺组织肿瘤坏死因子-α(TNF-α)含量,Western Blot法及q PCR法分别检测各组大鼠肺组织TLR4蛋白及mRNA水平。结果:与模型组相比,高、低剂量杆努尽烟均可改善慢性支气管炎大鼠呼吸系统症状,减轻肺组织炎症,降低慢支大鼠肺组织中TNF-α的水平,减少TLR4蛋白及mRNA的表达(P <0. 05),其中高剂量杆努尽烟效果更好。结论:苗药杆努尽烟可减轻慢性支气管炎模型大鼠呼吸道症状及肺组织炎症,其机制可能与下调大鼠肺组织TLR4及TNF-α表达水平有关。

Multiomics reveal human umbilical cord mesenchymal stem cells improving acute lung injury via the lung-gut axis

BACKGROUND Acute lung injury(ALI)and its final severe stage,acute respiratory distress syndrome,are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments.Gut microbiota homeostasis,including that in ALI,is important for human health.Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis.Human umbilical cord mesenchymal cells(HUC-MSCs)have attractive prospects for ALI treatment.This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora.AIM To explore the effects of HUC-MSCs on lipopolysaccharide(LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.METHODS C57BL/6 mice were randomly divided into four groups(18 rats per group):Sham,sham+HUC-MSCs,LPS,and LPS+HUC-MSCs.ALI was induced in mice by intraperitoneal injections of LPS(10 mg/kg).After 6 h,mice were intervened with 0.5 mL phosphate buffered saline(PBS)containing 1×10^(6) HUC-MSCs by intraperitoneal injections.For the negative control,100 mL 0.9%NaCl and 0.5 mL PBS were used.Bronchoalveolar lavage fluid(BALF)was obtained from anesthetized mice,and their blood,lungs,ileum,and feces were obtained by an aseptic technique following CO_(2) euthanasia.Wright’s staining,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,Evans blue dye leakage assay,immunohistochemistry,fluorescence in situ hybridization,western blot,16S rDNA sequencing,and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice,and the involvement of the lung-gut axis in this process was explored.One-way analysis of variance with post-hoc Tukey’s test,independent-sample Student’s t-test,Wilcoxon rank-sum test,and Pearson correlation analysis were used for statistical analyses.RESULTS HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury,and decrease mononuclear cell and neutrophil counts,protein concentrations in BALF and inflammatory cytokine levels in the serum,lung,and ileum of ALI mice.Especially,HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4,myeloid differentiation factor 88,p-nuclear factor kappa-B(NF-κB)/NF-κB,and p-inhibitorαof NF-κB(p-IκBα)/IκBαexpression levels in the lung,and raised the pulmonary vascular endothelial-cadherin,zonula occludens-1(ZO-1),and occludin levels and ileal ZO-1,claudin-1,and occludin expression levels.HUC-MSCs improved gut and BALF microbial homeostases.The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUCMSCs.Concurrently,the abundances of Oscillospira and Coprococcus in the feces of HUS-MSC-treated ALI mice were significantly increased.In addition,Lactobacillus,Bacteroides,and unidentified_Rikenellaceae genera appeared in both feces and BALF.Moreover,this study performed metabolomic analysis on the lung tissue and identified five upregulated metabolites and 11 downregulated metabolites in the LPS+MSC group compared to the LPS group,which were related to the purine metabolism and the taste transduction signaling pathways.Therefore,an intrinsic link between lung metabolite levels and BALF flora homeostasis was established.CONCLUSION This study suggests that HUM-MSCs attenuate ALI by redefining the gut and lung microbiota.

依托咪酯抑制TLR4/HMGB1通路保护脂多糖诱导的大鼠急性肺损伤

目的探讨依托咪酯通过调节TLR4/HMGB1通路对脂多糖诱导急性肺损伤的机制研究。方法将45只SD大鼠随机地分为对照组、脂多糖组、脂多糖+依托咪酯组,每组15只。HE染色显微镜下观察肺组织结构变化,并检测肺损伤指标(肺干湿重比),ELISA法检测肺组织炎症反应程度(IL-6及TNF-α),Western blot法检测肺组织中Toll样受体4(TLR4)及高迁移率族蛋白b1(HMGB1)蛋白表达。结果依托咪酯改善大鼠肺组织结构变化,降低湿/干重比、IL-6和TNF-α表达水平、抑制TLR4和HMGB1蛋白表达。结论依托咪酯对脂多糖诱导的急性肺损伤具有保护作用,且保护作用与其能够减轻炎症反应的能力有关,可能是通过TLR4/HMGB1途径实现。

Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury

Acute lung injury(ALI)is a severe inflammatory condition with a high mortality rate,often precipitated by sepsis.The pathophysiology of ALI involves complex mechanisms,including inflammation,oxidative stress,and ferroptosis,a novel form of regulated cell death.This study explores the therapeutic potential of andrographolide(AG),a bioactive compound derived from Andrographis,in mitigating Lipopolysaccharide(LPS)-induced inflammation and ferroptosis.Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI.The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells.In vivo,AG treatment markedly reduces lung edema,decreases inflammatory cell infiltration,and mitigates ferroptosis in lung tissues of LPS-induced ALI mice.These protective effects are mediated via the modulation of the Toll-like receptor 4(TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Molecular docking simulations identified the binding sites of AG on the TLR4 protein(Kd value:-33.5 kcal·mol^(-1)),and these interactions were further corroborated by Cellular Thermal Shift Assay(CETSA)and SPR assays.Collectively,our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway.This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

趋化因子受体4在高压氧致肺型氧中毒大鼠模型肺组织中含量的变化

目的 研究肺型氧中毒（pulmonary oxygen toxicity）大鼠肺组织损伤中趋化因子受体4（chemokine receptor4,CXCR4）的变化规律.方法 雄性健康SD大鼠30只,体质量200～ 220 g,按数字表法随机分为6组,每组5只.其中1组为常压空气对照组,该组大鼠暴露于自然大气环境中,禁食水,不进行任何加减压实验处理;另外5组分别在高压纯氧环境下暴露2、4、6、8、10 h后逐组出舱进行动物存活实验动物处理.实验动物氧舱底铺设新鲜钠石灰,100％氧气持续灌舱10 min,氧流量计测定舱内氧浓度达99％后,以0.1 MPa/min的速率匀速加压至0.23 MPa.持续微量通风,维持舱内氧浓度＞99％.观察各组大鼠肺组织病理改变,应用蛋白免疫印记法检测CXCR4,并与常压空气对照组对比.结果 随着氧暴露时间增加,肺组织出现淤血、水肿,出血程度不断加重.CXCR4表达在8h内随时间增加而增高,但在10h组表达有所下降.结论 高压纯氧暴露后大鼠发生了肺脏组织损伤,与CXCR4变化规律基本一致.

急性百草枯中毒大鼠肺组织Toll样受体4和核因子-κB表达的变化

目的观察急性百草枯（PQ）中毒大鼠肺组织中Toll样受体4（TLR4）和核因子．κB（NF-kB）mRNA表达的变化，探讨TLR4-NF-kB通路在急性PQ中毒肺损伤中的作用。方法30只雄性sD大鼠随机分为2组：生理盐水（NS）对照组（6只，NS腹腔注射），PQ染毒组（24只，腹腔注射PQ溶液，20mg／kg）。PQ染毒组分别在染毒后6、24、48h及72h麻醉处死，Ns对照组于处理后6h处死，进行肺组织HE染色，病理学观察，用实时定量PCR方法检测TLR4和NF-kB的mRNA表达情况，用ELISA方法测定肺组织中肿瘤坏死因子-α（TNF-α）、血清中IL-6含量。结果PQ染毒组大鼠肺组织病理表现为早期充血水肿明显，大量炎性细胞浸润。与NS对照组相比PQ染毒组肺组织中TLR4和NF．kBmRNA的表达量、TNF-α、IL-6含量在各时间点均有不同程度升高，差异均具有统计学意义（P〈0．01）。结论大鼠急性PQ中毒后肺组织中TLR4和NF．κBmRNA表达量、TNF-α、IL-6含量明显上调，TLR4-NF-kB通路参与了PQ中毒大鼠肺损伤的早期病理生理过程。

TTF-1、CDK4、EGFR在非小细胞肺癌组织中的表达及与临床病理特征的相关分析

目的 探讨甲状腺转录因子1(TTF-1)、细胞周期蛋白依赖性激酶4(CDK4)、表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)组织中的表达,并分析其与临床病理特征的关系。方法 选取2021年1月—2022年10月在驻马店市中心医院诊治的NSCLC患者115例,检测癌组织和癌旁组织TTF-1、CDK4、EGFR表达,并分析癌组织TTF-1、CDK4、EGFR表达与年龄、性别、肿瘤直径、肿瘤位置、肿瘤分期、分化程度、淋巴结转移、吸烟等临床病理特征的关系。结果 NSCLC患者癌组织TTF-1阳性率(58.26%vs 10.43%)、CDK4阳性率(92.17%vs 84.35%)、EGFR阳性率(64.35%vs 6.09%)明显高于癌旁组织(P<0.05)。NSCLC患者癌组织TTF-1阳性表达与年龄、性别、肿瘤直径、肿瘤位置、吸烟无关(P>0.05),与肿瘤分期、分化程度、淋巴结转移有关(P<0.05);NSCLC患者癌组织EGFR阳性表达与年龄、性别、肿瘤直径、肿瘤位置、吸烟无关(P>0.05),与肿瘤分期、分化程度、淋巴结转移有关(P<0.05);NSCLC患者癌组织CDK4阳性表达与年龄、性别、肿瘤直径、肿瘤位置、淋巴结转移、吸烟无关(P>0.05),与肿瘤分期、分化程度有关(P<0.05)。结论 TTF-1、CDK4、EGFR在NSCLC患者癌组织呈高表达,TTF-1、EGFR与NSCLC的发生、发展以及转移有关,CDK4与NSCLC的发生以及发展有关。

生长抑素对内毒素诱导感染性休克大鼠肺损伤的保护作用

目的基于Toll-样受体4/核因子кB(TLR4/NF-κB p65)信号通路探讨生长抑素(SST)对内毒素诱导感染性休克大鼠肺损伤的保护作用。方法将60只SD大鼠随机分为对照组、模型组[10mg/kg脂多糖(LPS)]、BAY11-7082组(LPS+10mg/kg BAY11-7082)、SST组(LPS+22μg/kg SST)和SST+BAY11-7082(LPS+SST)组各12只。注射LPS后12h,检测各组大鼠肺组织病理变化和细胞凋亡、肺组织湿/干质量(W/D)比值、LPS、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、TLR4、髓样分化蛋白抗原(MyD88)、p65、磷酸化的NF-кB抑制蛋白(p-IκB)和裂解天冬氨酸特异性半胱氨酸蛋白酶(cleaved Caspase)-3表达。结果与对照组比较,模型组大鼠肺组织W/D比值和细胞凋亡率升高,LPS、IL-6、IL-10和TNF-α水平升高,TLR4、MyD88、p65、p-IκB和cleaved Caspase-3表达升高(P<0.05);与模型组比较,BAY11-7082组和SST组肺组织病理学评分、W/D比值和细胞凋亡率降低,LPS、IL-6和TNF-α水平下降,IL-10水平升高(P<0.05),TLR4、MyD88、p65、p-IκB和cleaved Caspase-3蛋白表达下降(P<0.05);与SST组比较,SST+BAY11-7082组肺组织病理学评分、W/D比值和细胞凋亡率降低,LPS、IL-6和TNF-α水平下降,IL-10水平升高,TLR4、MyD88、p65、p-IκB和cleaved Caspase-3蛋白表达下降(P<0.05)。结论SST可以抑制TLR4/NF-κB信号通路,降低肺组织炎症反应,减轻内毒素诱导感染性休克大鼠肺损伤。

红景天苷对重症肺炎大鼠肺组织损伤的作用及可能机制

目的探讨红景天苷(salidroside,SAL)是否通过介导Toll样受体4/核转录因子-κB/NOD样受体蛋白3(TLR4/NF-κB/NLRP3)信号通路改善重症肺炎(severe pneumonia,SP)大鼠肺组织损伤。方法Wistar大鼠75只,随机选择15只作为假手术组,其余60只通过气管内滴注肺炎克雷伯菌(Klebsiella pneumoniae,Kp)悬液诱导构建SP大鼠模型。建模成功大鼠随机分为模型组、SAL低剂量组(30 mg/kg)、SAL高剂量组(60 mg/kg)和地塞米松(dexamethasone,DXMS)组(15 mg/kg),每组15只,假手术组和模型组均灌服等量生理盐水,连续7 d。检测肺组织湿干重比(Wet/Dry,W/D);HE和TUNEL染色观察各组大鼠肺脏组织形态及细胞凋亡情况;ELISA法检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中TNF-α、IL-1β、IL-6、IL-18及IL-10水平;Western blot检测肺组织中TLR4、髓样分化因子(myeloid differentiation factor 88,MyD88)、NF-κBp65、磷酸化NF-κBp65(phosphorylated NF-κBp65,p-NF-κBp65)、NLRP3蛋白相对表达水平。结果经气管滴注Kp悬液成功构建SP大鼠模型;与假手术组比较,模型组大鼠肺组织水肿严重,W/D值升高(P<0.05),肺泡结构松散不完整,肺泡壁水肿增厚,大量炎性细胞浸润,细胞凋亡率升高,BALF中炎性因子TNF-α、IL-1β、IL-6及IL-18水平升高,IL-10水平降低,肺组织中TLR4、MyD88、NF-κBp65、p-NF-κBp65及NLRP3蛋白相对表达水平升高(P<0.05);与模型组比较,SAL低、高剂量组及DXMS组大鼠肺组织病理损伤情况均逐渐改善,W/D值降低(P<0.05),肺泡结构逐渐完整,肺泡壁水肿程度逐渐减轻,细胞凋亡率降低,BALF中炎性因子TNF-α、IL-1β、IL-6及IL-18水平降低,IL-10水平升高,肺组织中TLR4、MyD88、NF-κBp65、p-NF-κBp65及NLRP3蛋白相对表达水平降低(P<0.05);低、高剂量SAL及DXMS改善SP大鼠肺组织损伤的作用效果表现为逐渐增强(P<0.05)。结论SAL可减少细胞凋亡,改善由Kp诱导的大鼠肺组织病理损伤,其作用机制可能与阻断TLR4/NF-κB/NLRP3信号通路激活,抑制炎性因子表达有关。