Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

Application of Serum Apelin and MMP-9 in Evaluation of Silicosis and Their Correlation with Lung Function

[Objectives]This study was conducted to explore the combination of serum Apelin and MMP-9 in the assessment of silicosis and their correlation with lung function. [Methods] From January 2020 to January 2021, eight patients with silicosis(including 3, 2 and 3 patients with silicosis in stages I, II and III respectively) were selected as the observation group, and eight persons frees of silicosis were selected as the control group during the same period. All patients were detected for serum APJ endogenous ligand(Apelin) of G protein-coupled receptor, matrix metalloproteinase-9(MMP-9) and pulmonary function indexes. The levels of serum Apelin and MMP-9 and lung function in the two groups were compared, and the correlation between serum Apelin and MMP-9 indexes and lung function was analyzed. [Results] The serum Apelin and lung function in the observation group were lower than those in the control group, and the level of MMP-9 in the observation group was higher than that in the control group, and the differences were statistically significant(P<0.05). The MMP-9 index in patients with silicosis in stage III was higher than those in patients with silicosis in stage II and stage I, and the MMP-9 index in patients with silicosis in stage II was higher than that in patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The serum Apelin and lung function indexes of patients with silicosis in stage III were lower than those of patients with silicosis in stage II and stage I, and the serum Apelin and lung function indexes of patients with silicosis in stage II were lower than those of patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The correlation analysis showed a positive correlation between serum Apelin and lung function indexes, and a negative correlation between MMP-9 and lung function indexes. [Conclusions] A lower serum Apelin and a higher MMP-9 value in patients with silicosis indicate severer lung function impairment, and the combined detection of serum Apelin and MMP-9 is conducive to effective evaluation of the disease of silicosis. The serum Apelin index was negatively correlated with silicosis, and the level of MMP-9 was positively correlated with silicosis, which could provide a scientific basis for clinical diagnosis and treatment.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

TNF-α and IL-1RA Polymorphisms and Silicosis Susceptibility in Chinese Workers Exposed to Silica Particles:A Case-Control Study

Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α （-238 and -308） and IL-1RA （＋2018） was performed using polymerase chain reaction-based restriction fragment length polymorphism （PCR-RFLP） and SYBR green-based quantitative polymerase chain reaction {qPCR）, respectively. Unconditional logistic regression model was used to estimate odds ratios （ORs） and their 95% confidential intervals （Cl） for SNPs. Results No significant differences were found between cases and controls in particles exposure length, body mass index （BMI）, and status of smoking and alcohol consumption except for age （P=O.O01） and blood type （P=0.042）. The frequencies of TNF-c（（-238） and IL-1RA （＋2018） genotypes in cases were significantly different from those in controls, （P=O.O01 and P=0.O02, respectively）, while a borderline significant difference was found in the frequencies of TNF-α（-308） between cases and controls （P=0.063）. The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNFα（-308）, TNF-α（-238） and IL-1RA （＋2018） were 2.8 （95% Ch 2.1-7.5）, 20.9 （95% Ch 2.8-236.4） and 4.0 （95% CI： 2.6-10.2）, respectively. Conclusion It is suggested that cytokine polymorphisms of TNF-ct （-238, -308） and IL-1RA （＋2018） are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.

Silicosis in Automobile Foundry Workers: A 29-Year Cohort Study

Objectives The purposes were to determine the relationship between silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing silicosis by a given length of employment and air concentrations of silica at worksites. Methods A 29-year cohort study was conducted, including all those employed for more than one year during January 1, 1980 to December 31, 1996 and all members of the cohort were followed-up to December 3 1, 2008. In total, 2 009 workers of an automobile foundry in Shiyan, Hubei province were recruited in the study, 1 300 at eight worksites including sand preparation, cast shakeout, and finishing, melting, moulding, core-making, overhead crane operation and pouring as exposed group, and the other 709 auxiliary workers at the same factory, such as electricians, inspectors, fitters, and so on, as control group. Person-years of observation were calculated by persons observed and years followed-up for each of them. Person-year incidence of silicosis and its relative risk （RR） or odds ratio （OR） and 95% confidence intervals （CI） among the workers were estimated, adjusted for relevant factors with logistic regression model using SPSS version 15.0 software. Results Totally, 2 009 workers were followed-up for 37 151 person-years and 48 cases of silicosis were found, with an overall incidence of 1.34 per thousand, 2.02 per thousand in exposed group, and 0.15 per thousand in control one. Risk of silicosis was significantly higher in the exposed group than that in the control one （RR=13.13, 95% CI 3.18-54.13）, higher in men than that in women （RR=13.92, 95% CI 1.92-100.93）. Risks of silicosis varied by job, highest in those exposed to cast shakeout and finishing （RR=28.14, 95% CI 6.43-123.11）, followed by those exposed to pouring （RR-22.23, 95% CI 5.01-98.55） in the foundry. Average length of employment at onset of silicosis was 25.94 years, and silicosis incidence increased with length of employment. Average age at onset of silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.

Combined silicosis and mixed dust pneumoconiosis with rapid progression: A case report and literature review

BACKGROUND Rapidly progressive pneumoconiosis(RPP) occasionally occurs in coal workers, particularly those with high exposure to silica. Here, we report the case of a 64-year-old male miller with RPP. CASE SUMMARY The patient had a persistent cough for one month and had been clinically diagnosed with pulmonary tuberculosis in 2011. He worked in a stone processing factory from the ages of 20 through 37 and has owned his own mill for the past 25 years. His chest radiograph showed significant increases in the size and number of lung nodules since his last follow-up in 2013. By percutaneous needle lung biopsy, the nodular lesions showed diffuse infiltration of phagocytic macrophages and birefringent crystals by polarizing microscopy. He was finally diagnosed with RPP of mixed dust pneumoconiosis combined with silicosis. CONCLUSION In this case, mixed dust pneumoconiosis with silicosis might be accelerated by persistent exposure to graindust from working in a mill environment.

The Relationship between Polymorphisms of Interleukin-4 Gene and Silicosis

Objective To explore the relationship between polymorphisms of interleukin-4 （IL-4） gene （-33, ＋45, intron3, ＋429, ＋448） and the susceptibility of silicosis. Methods A case-control study was carried out. 101 silicosis patients were selected as cases. As strictly matching, 121 of non silicosis workers were selected as the controls. The polymophisms of IL-4 （five locus） were detected by the method of polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques. Results The GA genotype in the IL-4＋429 locus and the CC genotype in the IL-4＋448 locus were found. The frequencies ofAA, GG and AG of IL-4＋45 locus in the cases were 55.4%, 10.9%, and 33.7% and in the controls were 62.0%, 12.6%, and 26.4%. The differences between cases and controls were not significant. The frequencies of B1B1, B2B2, and B1B2 of intron3 VNTR locus in the cases were 73.3%, 1.0%, and 25.7% and in the controls were 68.6%, 1.7%, and 29.8%. The differences were not significant. The frequencies of TT, CC, and CT in -33 locus in the cases were 55.4%, 11.9%, and 32.7% and in the controls were 69.4%, 4.1%, and 26.4%. The differences were significant （P=0.034）. Conclusion The relationship between genetic polymorphism of IL-4-33 site and silicosis has been found and -33TT is a protective genotype for silicosis.

Modified Glasgow Prognostic Score, and Neutrophil/lymphocyte and Platelet/lymphocyte Ratios in Different Stages of Silicosis

Until now, although comprehensive management strategies have improved treatment, there are no treatments to alleviate symptoms and slow disease progression[1]. In the past few decades, there has been increasing evidence that inflammation plays a very important role in silicosis. Injury-induced inflammation is an effective strategy to remove harmful stimuli and initiate a healing process. However, it might be harmful to the organism and result in a permanent disease state if the inflammation is prolonged[2].

The Effects of Tetrandrine (TT) and Polyvinylpyridine-N-Oxide (PVNO) on Gene Expression of Type Ⅰand Type ⅢCollagens during Experimental Silicosis

In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis

Serum neuron-specific enolase:A promising biomarker of silicosis

BACKGROUND Silicosis is a type of chronic pulmonary fibrosis caused by long-term inhalation of silica dust particles.There has been no ideal biomarker for the diagnosis and differential diagnosis of silicosis until now.Studies have found that elevated neuron-specific enolase(NSE)concentration in the serum of silicosis patients is helpful for diagnosis and severity assessment of the disease.However,the number of cases in these studies was not enough to arouse attention.AIM To investigate the clinical significance of serum NSE in the diagnosis and staging of silicosis.METHODS From January 2017 to June 2019,326 cases of silicosis confirmed in Quanzhou First Hospital Affiliated to Fujian Medical University were included in the silicosis group.A total of 328 healthy individuals or medical patients without silicosis were included in the control group.Serum NSE concentrations of all subjects were determined by electrochemical luminescence.RESULTS There were no significant differences in sex,age,smoking index and complications between the silicosis and control groups.The mean serum NSE concentration was 26.57±20.95 ng/mL in the silicosis group and 12.42±2.68 ng/mL in the control group.The difference between the two groups was significant(U=15187,P=0.000).Among the 326 patients with silicosis,103 had stage I silicosis,and the mean serum NSE concentration was 15.55±6.23 ng/mL.The mean serum NSE concentration was 21.85±12.05 ng/mL in 70 patients with stage II silicosis.The mean serum NSE concentration was 36.14±25.72 ng/mL in 153 patients with stage III silicosis.Kruskal-Wallis H test suggested that the difference in serum NSE concentration in silicosis patients in the three groups was significant(H=130.196,P=0.000).Receiver operating characteristic curve analysis indicated that the area under the curve was 0.858(95%confidence interval:0.828-0.888;P=0.000).When the NSE concentration was 15.82 ng/mL,the Jorden index was the largest,the sensitivity was 72%,and the specificity was 90%.CONCLUSION Serum NSE concentration may be a promising biomarker for the diagnosis and assessment of severity of silicosis.

Effects of respiratory rehabilitation training combined with Corbrin Capsule on the inflammatory response and pulmonary fibrosis in patients with silicosis complicated by COPD

Objective: To explore the effects of respiratory rehabilitation training combined with Corbrin Capsule on the inflammatory response and pulmonary fibrosis in patients with silicosis complicated by COPD. Methods: A total of 80 patients with silicosis complicated by COPD who were treated in our hospital between January 2013 and December 2016 were selected as the research subjects and randomly divided into control group (n=40) and observation group (n=40). Control group were treated with Corbrin Capsule on the basis of routine treatment, and observation group were treated with respiratory rehabilitation training combined with Corbrin Capsule on the basis of routine treatment. The differences in serum levels of inflammatory factors and pulmonary fibrosis indexes were compared between the two groups before intervention, after 6 months of intervention and after 1 year of intervention. Results: Before intervention, there was no statistically significant difference in serum levels of inflammatory factors and pulmonary fibrosis indexes between the two groups. After 6 months of intervention and after 1 year of intervention, serum inflammatory factors IL-6, IL-8, IL-12, IL-17, IL-18 and MCP-1 levels of observation group were lower than those of control group;serum pulmonary fibrosis indexes PCⅢ, LN, HA, ICAM-1 and HO-1 contents were lower than those of control group. Conclusion: Respiratory rehabilitation training combined with Corbrin Capsule therapy can effectively reduce the systemic inflammatory response and inhibit the pulmonary fibrosis process in patients with silicosis complicated by COPD.

A Biochemical Study on Combined Treatment of Experimental Silicosis with Tetradrine-PVNO and Tetradrine-QOHP in Rats

A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), monoamine oxidase (MAO) and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or tetradrine-QOHP were measured. The values obtained were compared with the untreated silicotic rats. It was found that the silicotic rats that received tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no significant change in MAO. The PLD in plasma of silicotic rats that received tetradrine-QOHP were elevated significantly, but PLG and MAO did not change appreciably. These findings suggest that the combined use of tetradrine-PVNO and tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats

Natural Course of Silicosis in Dust-exposed Workers

To provide a scientific basis for determining the health surveillance period of dust-exposed workers, data of a retrospective cohort study was re-analyzed with emphasis on natural course of silicosis. 33640 workers exposed to silica dust who were employed for at least 1 year from 1972 to 1974 in twenty Chinese mines or pottery factories were included as subjects, and were followed up till December 31, 1994. The cohort included subjects from 8 tungsten mines, 4 tin mines and 8 pottery factories. Our results showed that the mean latency of silicosis, for all the cases of the cohorts, was 22.9±9.8 y. 52.2 % of silicosis was diagnosed approximately 9.1±5.7 y after the dust exposure had ceased. The progression rates of silicosis from stage Ⅰ to Ⅱ and from stage Ⅱ to Ⅲ were 48.2 % and 18.5 %, and the duration was 4.1±0. 2 and 6.8±0.2 y, respectively. The survival times of silicosis stage Ⅰ , Ⅱ and Ⅲ, from the year of diagnosis to death, were 21.5, 15.8 and 6.8 years, respectively. There was 25 % of the silicosis patients whose survival time was beyond 33 y. The mean death age of all silicosis cases was 56.0 y. The death age inereased to 65.6 y in the middle of 1990s. Among dust-exposed workers, subjects who became suspected case （0^＋ ） accounted for 15.0 %. 48.7 % of the suspected silicosis cases developed to silicosis, and the average year from the time of being suspected of the disease to the first stage of silicosis was 5.1y. The natural characteristics, as mentioned above, varied with different mines and factories. We are led to conclude that silicosis is chronic in nature, but progress quickly. As a serious occupational disease it significantly reduces the life span of exposed workers. The study of its natural history is of importance for the development of health surveillance criteria for dust-exposed workers.

Effect of oxidative stress on development of silicosis

AIM: To investigate the changes of oxidative stress indicators in the serum of silicosis patients and explore the mechanism of silicosis development.METHODS: Two hundred workers who were exposed to silica dust for more than one year were recruited as dust-exposed group, 100 non-dust-exposed subjects served as control group, 32 patients with suspected 0+ silicosis as observation group, and 130 silicosis patients were taken as the silicosis group. Indicators of oxidative stress, including superoxide dismutase(SOD), nitric oxide(NO), serum glutathione peroxidase(GSHPx), total antioxidant capacity(T-AOC), nitric oxide synthase(NOS), and lipid malondialdehyde(MDA), were determined in all the groups. RESULTS: Compared with the control group, NO and GSH-Px in dust-exposed group and silicosis group increased, and SOD decreased significantly(81.162± 35.176, 270.469 ± 39.228 and 68.209 ± 21.528, respectively, P = 0.004, P = 0.002, P = 0.005). Compared with the control and dust-exposed group, T-AOC, NOS and MDA in silicosis group increased significantly(13.048 ± 4.153, 36.201 ± 7.782 and 5.054 ± 1.204, respectively, P = 0.018, P = 0.022, P = 0.011). Compared with dust-exposed group, GSH-Px in the silicosis group increased significantly(270.469 ± 39.228, P = 0.002). GSH-Px in phase Ⅲ silicosis was significantly higher than in phase Ⅰsilicosis(290.750 ± 39.129, P = 0.021). Pearson correlation analysis showed that serum GSH-Px was positively correlated with silicosis staging, length of dust exposure and type of occupation(47.109 ± 8.015, P = 0.001).CONCLUSION: The imbalance of oxidative and antioxidation system is associated with the development of silicosis. The surveillance of oxidative stress indicators will benefit the prognosis of silicosis patients.

Exploring the key pathways of tetrandrine in the treatment of early silicosis based on bioinformatics and in vitro experiments

Objective:Exploring the key pathways affecting the development of early silicosis based on bioinformatics and in vitro experiments.Method:Collecting differentially expressed genes in silicosis patients through literature mining;Collecting differentially expressed genes in silicon dioxide infusion mice by using a high-throughput gene expression database(GEO);Obtaining disease targets related to silicosis by means of online human Mendelian genetic database(OMIM),GeneCards and comparative toxicgenomics database(CTD);differentially expressed genes and disease targets were subjected to gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genome(KEGG)enrichment analysis via R-package and Metascape platforms,respectively.The Schrödinger and Pymol software were used for molecular docking and modification.Silicon dioxide-stimulated macrophages and epithelial cells were modeled and analyzed by PCR and western blot(WB).Result:2065 differentially expressed genes in silicosis patients,2291 differentially expressed genes in rat infused with silicon dioxide,and 803 targets for silicosis-related diseases were screened out.GO enrichment analysis mainly involves G protein-coupled receptor binding,the regulation of inflammatory response,and participation in immune response.The enrichment analysis of KEGG pathway mainly included ECM-receptor interaction,TNF signaling pathway,and IL-17 signaling pathway.IL-17 signaling pathway was screened out from different genes and disease targets,indicating that IL-17 signaling pathway might be the key pathway for the development of silicosis.Molecular docking results showed that the silicosis drug tetrandrine had good binding effect with the RAF/MEK/ERK pathway in the IL-17 signaling pathway.Cellular experiments showed that tetrandrine reduced the expression of inflammatory factors such as IL-6 and TGF-βin macrophages by regulating the RAF/MEK/ERKpathway,and inhibited the epithelialmesenchymal transition and expression of inflammatory factors in epithelial cells.Conclusion:Tetrandrine regulates the inflammatory response and epithelial-mesenchymal transition(EMT)through the RAF/MEK/ERK pathway and thus affects the early progression of silicosis.

Studies on Structural Changes of Collagen in Silicosis

In order to provide scientific information on the prevention and treatment of silicosis,studies about changes of silicotic collagen in lungs were carried out. In this paper, we present experiments about the structural changes of collagen in silicotic lungs of rats and patients. These included electron microscopy, circular dichroism and infrared spectroscopy studies of collagen fibers. The results indicated that fibers of silicotic collagen were shorter in length, smaller in diameter and decreased in α-helix content. The -Si-O-R- group and -OH group were found increased and -C-C- backbone shortened. The increase of -Si-O-R-group indicated that silica formed linking bridges between collagens which may be the cause of progressive enlargement of nodules

The Effects of N-acetyl-seryl-aspartyl-lysyl-proline on Expression of NF-κb and MCP-1 in Rats with Silicosis

In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.

急性硅肺小鼠模型系统评价

目的基于滴鼻法建立急性硅肺小鼠模型评价方法。方法小鼠麻醉后经鼻吸入的方法给予单次60μl二氧化硅50 mg/ml混悬液复制硅肺小鼠模型,以肺系数、肺干湿比、HE染色和免疫组织化学等作为硅肺小鼠肺损伤评价指标,Masson染色作为纤维化评价指标。结果与对照组相比,硅肺模型组小鼠在滴鼻1~5 d小鼠体重显著下降,运动能力有明显区分,且体重下降与运动距离存在显著相关性。硅肺模型组31 d,肺组织病理学观察到致密的斑片状病灶,提示肺部炎症脓肿并形成硅结节,伴有巨噬细胞和硅颗粒聚集;Masson染色显示纤维化显著,与二氧化硅吸入量呈剂量效应关系。结论采用单次经鼻吸入二氧化硅混悬液,30 d成功建立急性硅肺小鼠模型。

二氧化硅所致急性肺损伤大鼠肺部菌群的特征及相关性分析

目的:探讨二氧化硅所致急性肺损伤大鼠模型的潜在生物学机制。方法:采用随机数字表法,将SD雄性大鼠划分为正常组和二氧化硅模型组。正常组经气管灌注1 mL生理盐水,模型组经气管灌注等体积50 g/L二氧化硅混悬液。7 d后收集大鼠肺组织和血清,HE染色观察肺组织病理学特征,免疫组化检测肺组织核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)和消皮素D(GSDMD)蛋白表达,ELISA法检测血清炎症因子白细胞介素1β(IL-1β)、IL-18和肿瘤坏死因子α(TNF-α)水平;从肺组织中提取细菌DNA,经16S核糖体RNA基因测序描述肺部菌群组成变化,通过生物信息学分析比较正常组与模型组菌群结构差异。结果:与正常组相比,模型组大鼠体重增长率和肺指数有显著差异;模型组大鼠肺组织HE染色可见肺泡结构破坏,炎性细胞增多;模型组大鼠肺组织NLRP3和GSDMD蛋白表达水平均显著升高,血清IL-1β、IL-18和TNF-α水平均显著升高。与正常组相比,模型组丰度增加的肺部菌群为双歧杆菌(Bifidobacterium)、Clostridium sensu stricto 1和副萨特氏菌(Parasutterella)。Spearman相关性分析显示,肺组织NLRP3/GSDMD和血清IL-1β/TNF-α水平与Parasutterella丰度呈正相关。结论:二氧化硅所致急性肺损伤的病理机制可能与肺部菌群结构差异和炎症水平升高有关。因此,调节肺部菌群可能为防治二氧化硅引起的急性肺损伤提供新的思路。