Impact of emerging pollutants on pulmonary inflammation in asthmatic rats: ethanol vapors and agglomerated TiO2 nanoparticles

Context: Titanium dioxide nanoparticles (nano-TiO₂) and ethanol vapors are air contaminants with increasing importance. The presence of a pathological pulmonary condition, such as asthma, may increase lung susceptibility to such contaminants.

Objective: This study aimed to investigate if exposure to inhaled ethanol vapors or nano-TiO₂ can modulate the rat pulmonary inflammatory response resulting from an allergic asthmatic reaction.

Materials and methods: Brown Norway rats were sensitized (sc) and challenged (15?min inhalation, 14 days later) with chicken egg ovalbumin (OVA). Leukocytes were counted in bronchoalveolar lavages (BAL) performed at 6, 24, 36, 48 and 72?h following the challenge and either after ethanol exposures (3000 ppm, 6?h/day, daily) or at 48?h (peak inflammation) for nano-TiO₂ exposures (9.35?mg/m³ aerosol for 6 and 42?h after the OVA challenge). For the nano-TiO₂ exposures, plasma and BAL cytokines were measured and lung histological analyzes were performed.

Results: Exposure to ethanol did not significantly affect BAL leukocytes after OVA challenge. Exposure to nano-TiO₂ significantly decreased BAL leukocytes compared to OVA-challenged controls. Plasma and BAL IL-4, IL-6, and INF-γ levels were also decreased in the nano-TiO₂ group.

Discussion: While ethanol vapors do not modify the pulmonary inflammation in rats during an asthmatic response, a surprising protective effect for agglomerated nano-TiO₂ was observed. A putative mechanistic basis involving a decrease in the Th2 response caused by OVA is proposed.

Conclusion: Allergic pulmonary inflammation is not up-regulated by inhalation of the pollutants ethanol and nano-TiO₂. On the contrary, nano-TiO₂ decreases lung inflammation in asthmatic rats.     

Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats

Abstract

Context: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve liver ischemia-reperfusion-induced injury in rats.

Objective: This study was designed to determine whether the recombinant BPTI (rBPTI) can prevent the chronic liver injury induced by CCl₄ in rats.

Materials and methods: Fifty male Wistar rats were divided into five groups. Rats were treated with 40% CCl₄ at a dose of 2?ml/kg body weight twice a week subcutaneously for 12 weeks. In the 8th week, they were administered intraperitoneally with rBPTI (80 MU/kg), BPTI (80 MU/kg) or hepatocyte growth-promoting factor (pHGF; 100?mg/kg) daily for the next 4 weeks.

Results: rBPTI significantly prevented the disruption of liver function of alanine aminotransferase (ALT; 172.7?±?18.16 versus 141.2?±?15.28, p?=?0.003), aspartate aminotransferase (AST; 225.10?±?36.54 versus 170.06?±?27.14, p?=?0.007) and hydroxyproline (Hyp; 1.14?±?0.27 versus 0.62?±?0.17, p?=?0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive substances (TBARS; 1.15?±?0.16 versus 0.87?±?0.15, p?=?0.003) and increased the activities of superoxide dismutase (SOD; 6.07?±?0.95 versus 7.75?±?1.12, p?=?0.007). rBPTI reduced the production of cytokines of IL-1β and TGF-β. The hepatocyte necrosis, fibrosis, fatty degeneration and inflammatory cell infiltration were ameliorated by rBPTI administration.

Conclusion: This study demonstrated that rBPTI exerted a hepatoprotective effect on chronic liver fibrosis induced by CCl₄, which suggests that rBPTI may have the potential application for chronic liver injury induced by drugs metabolism and toxic substances.     

Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory,apoptotic and growth mediators in experimental rats

Context: Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors.

Aim: The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models.

Materials and methods: A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters.

Results: NOF (2 and 4%, w/w) treatment showed a significant decrease (p?<?0.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p?<?0.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p?<?0.05) restored by NOF. Treatment produced a significant increase (p?<?0.05) in tensile strength, hydroxyproline content, and protein content. TNF-α, IL-1β, IL-6, IL-8, NF-κB, smad-7, and Bax mRNA expression were significantly down-regulated (p?<?0.05) by NOF, whereas polymerase gamma (pol-γ), smad-3, VEGF and TGF-β, and collagen-1 mRNA expressions were significantly up-regulated (p?<?0.05) by NOF. Histological alterations in wound skin were also restored by NOF.

Conclusion: NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-κB, TNF-α, and ILs), apoptotic (pol-γ and Bax), and up-regulated growth factor (VEGF and TGF-β) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.     

Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling

Context: One approach to protect against liver fibrosis is the use of herb-derived natural compounds, such as hydroxysafflor yellow A (HSYA). The antifibrosis effect of HYSA against liver fibrosis has been investigated; however, its mechanisms have not yet been entirely revealed.

Objectives: To study the protective effects of HSYA on liver fibrosis induced by carbon tetrachloride (CCl₄) and a high-fat diet (HFD), and to determine the mechanism of action of HSYA.

Materials and methods: CCl₄ and HFD were used to mimic liver fibrosis in rats, and serum biochemical indicators were determined. The antifibrosis effects of HSYA were evaluated and its mechanisms were investigated by histopathological analysis, immunohistochemical staining, enzyme-linked immunosorbent assays, real-time-PCR, and western blotting.

Results: HSYA reduced CCl₄- and HFD-mediated liver fibrosis and ameliorated serum biochemical indicator, downregulated the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) (0.31?±?0.03 protein, 0.59?±?0.02 mRNA) and transformin growth factor-β1 (TGF-β1) (0.81?±?0.02 protein, 0.58?±?0.04 mRNA), and upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) (1.57?±?0.13 protein, 2.48?±?0.19 mRNA) and matrix metallopeptidases-2 (MMP-2) (2.31?±?0.16 protein, 2.79?±?0.22 mRNA) (p?Discussion and conclusion: These data demonstrate a novel role for HSYA in inhibiting CCl₄- and HFD-mediated liver fibrosis, and reveal that PPAR-γ and p38 MAPK signaling play pivotal roles in the prevention of liver fibrosis induced by CCl₄ and HFD.     

Euxanthone inhibits lipopolysaccharide-induced injury,inflammatory response,and MUC5AC hypersecretion in human airway epithelial cells by the TLR4/MyD88 pathway

Asthma progression is involved in airway epithelial dysfunction, airway inflammatory response, and mucus hypersecretion. Euxanthone has been found to exhibit cytotoxic activity on several human diseases, such as neurological disorders and cancers. Our study aimed to explore the influence of euxanthone on lipopolysaccharide (LPS)-induced injury, inflammatory response, and mucin 5AC (MUC5AC) hypersecretion in human airway epithelial cells (AECs). Network pharmacology analysis was carried out to analyze the drug targets and key pathways of euxanthone against asthma. Cell injury was evaluated by CCK-8, Lactate dehydrogenase (LDH) release assay, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The production of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and MUC5AC was measured using enzyme-linked immunosorbent assay (ELISA). MUC5AC mRNA expression was detected by qRT-PCR. Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein expression was examined by western blot analysis. Venn diagram showed 14 overlapping targets between euxanthone and asthma. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, we focused on TLR signaling pathway. LPS exposure evoked viability reduction, increased LDH release and apoptosis, and induced production of inflammatory cytokines (IL-6, IL-8, and MCP-1) and MUC5AC hypersecretion in human AECs, which were alleviated by euxanthone. Mechanistically, we validated that euxanthone attenuated LPS-induced activation of TLR4/MyD88 pathway in AECs. Moreover, inhibition of the TLR4/MyD88 pathway enhanced the inhibitory effect of euxanthone on LPS-induced cell injury, inflammatory response and MUC5AC expression. In conclusion, euxanthone attenuated LPS-induced cell injury, inflammatory response, and MUC5AC expression in AECs by inhibiting the activation of TLR4/MyD88 pathway.     

Effects and mechanisms of pirfenidone,prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models

Context: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown.

Objective: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF.

Materials and methods: Rat IPF model was established by endotracheal injection of 5?mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100?mg/kg once daily), prednisone (H, 5?mg/kg once daily) and acetylcysteine (N, 4?mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay.

Results: After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p?p?p?r?=??0.506, p?r?=?-0.676, p?r?=??0.590, p?r?=??0.530, p?r?=??0.553, p?Discussion and conclusion: Pirfenidone, prednisone and acetylcysteine can inhibit airsacculitis and pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.     

Thrombin promotes airway remodeling via protease-activated receptor-1 and transforming growth factor-β1 in ovalbumin-allergic rats

Abstract

Background: Protease-activated receptor-1 (PAR-1) is widely distributed in platelets and involved in coagulation cascade activated by thrombin. In this study, we intend to explore the role of PAR-1 in the process of thrombin-inducing transforming growth factor-β1 (TGF-β1) to promote airway remodeling in ovalbumin (OVA)-allergic rats.

Materials and methods: A rat model of chronic asthma was set up by systemic sensitization and repeated challenge to OVA. The doses of thrombin, recombinant hirudin, PAR-1 inhibitor ER-112780-06 varied for different groups. We evaluated the bronchoalveolar lavage fluid (BALF) concentration of thrombin in these groups. The protein and gene expression of PAR-1 was assessed and the expression of TGF-β1 was also detected.

Results: The PAR-1 mRNA level and the protein level were higher in the airway of asthmatic rats than those of normal rats, and were significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was strengthened by thrombin but weakened by thrombin inhibitor and PAR-1 antagonist. Expression of TGF-β1 protein in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and PAR-1 antagonist treatment.

Conclusion: The expression of PAR-1 is regulated by thrombin that induces the expression of TGF-β1 to promote airway remodeling via PAR-1 in OVA-allergic rats.     

Fine PM induce airway MUC5AC expression through the autocrine effect of amphiregulin

Particulate pollution is suspected to contribute to obstructive lung diseases characterized by chronic inflammation, mucus hypersecretion and bronchial remodeling. Our aim was to study the effect of real-world particulate matter (PM) on the expression of a mucin, MUC5AC, focusing on the role of the epidermal growth factor receptor (EGFR) pathway. MUC5AC induction was studied in vivo in mice trachea and in vitro in human bronchial epithelial cells (HBEC) exposed to urban fine PM. Fine PM were able to induce MUC5AC mRNA in mice trachea after 48?h of exposure (50?μg PM/mouse), and MUC5AC mRNA and protein in HBEC after 24?h of exposure (from 5?μg PM/cm²). It was associated with the increased expression of amphiregulin (AREG), an EGFR ligand. Experiments with conditioned media (media from PM-treated cells) demonstrated the involvement of AREG on MUC5AC induction as MUC5AC induction by media from PM-treated cells was prevented in the presence of either EGFR- or AREG-neutralizing antibodies. The effect of an inhibitor of a metalloprotease involved in the AREG shedding confirmed the autocrine loop made by AREG leading to MUC5AC induction by fine PM. We also demonstrated that IL-8 pro-inflammatory cytokine induction was dependent on the same autocrine mechanisms. We demonstrate for the first time that MUC5AC expression and production is increased by short-term exposure to fine PM through an autocrine effect of AREG. Our study provides mechanistic explanations to the exacerbation of obstructive lung diseases induced by particulate pollution characterized by mucus hypersecretion and chronic inflammation.     

Treg responses are associated with PM2.5-induced exacerbation of viral myocarditis

Abstract

The adverse cardiovascular events induced by ambient fine particles (PM_2.5) are paid more attention in the world. The current study was conducted to explore the mechanisms of T regulatory cells (Treg) responses in PM_2.5-induced exacerbation of viral myocarditis. The male BALB/c mice were administered an intratracheal (i.t.) instillation of 10?mg/kg b.w. PM_2.5 suspension. Twenty-four hours later, the mice were injected intraperitoneally (i.p.) with 100?μl of coxsackievirus B3 (CVB3) diluted in Eagle's minimal essential medium (EMEM). Seven days after the treatment, serum, splenetic, and cardiac tissues were examined. The results showed that pre-exposure to PM_2.5 aggravated the cardiac inflammation in the CVB3-infected mice along with an increase of Treg cells in the spleen. The mRNA expressions of interleukin-6 (IL-6), TNF-α, transforming growth factor-β (TGF-β), and Foxp3 were up-regulated in the PM_2.5-pretreated mice than that in the CVB3-treated mice. Similar results were found in the sera. In addition, compared with the CVB3-treated mice, the cardiac protein expression of TGF-β increased in the PM_2.5-pretreated mice. These results demonstrated that preexposure to PM_2.5 exacerbated virus-induced myocarditis possibly through the depression of the immune response and increase of inflammation in myocardium through the Treg responses.     

Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice

Context: Our previous study showed that the interleukin-17 (IL-17) concentration in lung tissue and in bronchoalveolar lavage fluid (BALF) of rats with tobacco-smoke-induced chronic obstructive pulmonary disease (COPD) was higher than that of control group. However, whether IL-17 inhibitor could decrease the effect of tobacco smoking is not known yet.

Objectives: To investigate the significance of IL-17 antibodies (Ab) in tobacco-smoke-exposed (TSE) mice.

Materials and methods: Male C57/BL6 mice were randomly divided into three groups: TSE group, TSE + anti-IL-17 Ab group, and control group. The number of cells in BALF and the concentrations of IL-17, IL-6, IL-8 and MUC5AC in BALF and lung tissue homogenate were measured. Pulmonary function was measured by pressure sensors, and histologic analysis of the lungs was done in each group.

Results: Lung function tests in TSE + anti-IL-17 Ab group were the same compared with TSE group (P?>?0.05). The total cell count and the number of neutrophil cells in BALF were significantly higher in TSE group than the normal control group (P?<?0.01). Compared with the TSE group, the total cell count in TSE + anti-IL-17 Ab group was decreased, and the percentage of neutrophils in BALF was highly decreased (P?<?0.01). Airway inflammation was alleviated in TSE + anti-IL-17 Ab group by histologic analysis. The concentrations of IL-17 in lung tissue were significantly lower in TSE + anti-IL-17 Ab group than in TSE group (P?<?0.01). IL-17 was mainly expressed in the epithelial cells in the airways of TSE mice. The concentration of IL-6, IL-8 and MUC5AC in BALF was decreased in TSE + anti-IL-17 Ab group compared with TSE group.

Discussion and conclusions: These data support a potential role for IL-17 in airway neutrophilic inflammation in TSE mice. Anti-IL-17 decreased the number of neutrophils as well as the concentration of MUC5AC in the BALF and attenuated neutrophilic airway inflammation.     

Emodin inhibits ATP-induced IL-1β secretion,ROS production and phagocytosis attenuation in rat peritoneal macrophages via antagonizing P2X7 receptor

Context: Previous in vitro studies have demonstrated that emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), an anthraquinone derivative from the rhizome of Rheum palmatum L., can inhibit the activation of P2X₇ receptors (P2X₇R) as a potential antagonist. However, the effects of emodin on P2X₇R-related inflammatory processes remain unclear.

Objective: This study aimed to investigate the effects of emodin on different inflammation responses of macrophages induced by ATP, the natural ligand of P2X₇R.

Materials and methods: Rat peritoneal macrophages were treated with millimolar ATP and emodin (0.1, 0.3,?1,?3,?10?µM) or brilliant blue G (BBG, 0.1,?1,?10?µM). Cytosolic Ca²⁺ concentration ([Ca²⁺]_c) was detected by fluorescent Ca²⁺ imaging. Interleukin-1β (IL-1β) release was measured by rat IL-1β ELISA kits. Reactive oxygen species (ROS) generation was examined by dihydroethidium (DHE) fluorescent staining. Phagocytic activity was tested by neutral red uptake assay.

Results: We found that the [Ca²⁺]_c increase evoked by ATP (5?mM) was inhibited by emodin, in a dose-dependent manner with IC₅₀ of 0.5?μM. Furthermore, emodin reduced the IL-1β release induced by ATP (2?mM) in lipopolysaccharide (LPS)-activated macrophages, with an IC₅₀ of 1.6?μM. Emodin also strongly suppressed the ROS production and phagocytosis attenuation triggered by ATP (1?mM), with IC₅₀ values of 1?μM and 0.7?μM, respectively. Besides, BBG, a specific antagonist of P2X₇R, exhibited similar suppressive effects on these inflammation responses.

Conclusion: These results showed the inhibitory effects of emodin on ATP-induced [Ca²⁺]_c increase, IL-1β release, ROS production and phagocytosis attenuation in rat peritoneal macrophages, by inhibiting the activation of P2X₇R.     

Pre-clinical pharmacokinetics of the acridine antitumour candidate AC04 and its 1-oxo-metabolite plasma profile

1. This work aimed to investigate plasma pharmacokinetics and tissue distribution of a new acridine derivative 5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione (AC04) and its 1-oxo-AC04 metabolite disposition in Wistar rats.

2. After a single AC04 1.5?mg/kg intravenous (i.v.) bolus dose, blood samples were taken up to 120?h. Plasma samples were deproteinization, and AC04 and metabolite were quantified by validated liquid chromatography in tandem with mass spectrometry method. Protein binding was determined by ultrafiltration. AC04 tissue disposition was evaluated after i.v. bolus dose.

3. Individual AC04 concentration–time profiles were best fitted by a two-compartment model showing CL_tot of 3.4?±?3.4?L/h/kg, Vd_SS of 137.9?±?91.4?L/kg, AUC_0–∞ of 788?±?483 ng·h/mL and a t_1/2 of 45.5?±?31.5?h. Protein binding was 98.1?±?1.6%. AC04 showed higher penetration into the lung, spleen and liver, with AUC_0–96 of 798,443, 263,211 and 303,722 ng·h/mL, respectively. The 1-oxo-AC04 metabolite represented 10% of AC04 plasma concentration, showing a t_1/2 of 23.2?±?10.4?h.

4. These results suggest that, despite the small free plasma fraction, AC04 penetrates extensively reaching high concentrations in most tissues residing for a long time, which is important for its activity on solid tumours. All results combined indicate that AC04 is potentially a good antitumour candidate.

     

The increases in relative mRNA expressions of inflammatory cytokines and chemokines in splenic macrophages from rats exposed to multi-walled carbon nanotubes by whole-body inhalation for 13 weeks

Abstract

Background: The toxicity of multi-walled carbon nanotubes (MWCNT) may be related to the immune system. The objective of this study was to obtain information for immunotoxic mechanisms of MWCNT in situ.

Methods: Using whole-body inhalation, male and female rats were exposed to 0, 0.2, 1 or 5?mg MWCNT/m³ for 13 weeks. Thereafter, spleens were recovered from the rats. Real-time PCR was done to assess expression of TNFα, IL-1β, IL-6, IL-10, MCP-1 and MIP-1α mRNA in the splenic macrophages; splenic T-lymphocytes were examined for IL-2 and TGF-β₁ mRNA expression.

Results: The relative expression of IL-1β mRNA in the cells from female rats exposed to 5?mg MWCNT/m³ was significantly higher than that in control cells. For IL-6 and IL-10, cells from rats in the 0.2 and 5?mg MWCNT/m³ had significantly higher mRNA expressions than did cells from controls. Expression of IL-1β, IL-6 and TNFα genes in cells from males in all exposure groups were higher than in control cells. Expression of MIP-1α in the cells from female 5-mg group was significantly higher than that in cells in the control. Only IL-2 was expression reduced, i.e. cells from male and female rats in all MWCNT groups had significantly lower mRNA expressions than control cells.

Conclusions: Systemic inflammation would likely occur in rats (or other hosts) exposed to MWCNT via inhalation due to increases in the expression of inflammatory cytokines in splenic macrophages. Moreover, decreases in IL-2 expression in T-lymphocytes may be critical to the potential reductions in anti-tumor responses in MWCNT-exposed hosts.     

15-Deoxy-Δ-prostaglandin J2 inhibits fibrogenic response in human hepatoma cells

Liver fibrosis can be induced by environmental chemicals or toxicants, and finally stimulates fibrogenic cytokines expression, such as transforming growth factor-β (TGF-β) and its downstream mediator connective tissue growth factor (CTGF). 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) is a metabolite of arachidonic acid, can act as a peroxisome proliferator-activated receptor γ (PPARγ) ligand, and function as either anti-inflammatory or inflammatory agents in different cell types. In this study, CTGF was detected in three human hepatoma cell lines, Hep3B, HepG2, and Huh-7, and it was up-regulated by TGF-β. 15d-PGJ₂ significantly inhibited TGF-β-induced CTGF protein and mRNA expressions, and promoter activity in hepatoma cells. 15d-PGJ₂ suppressed TGF-β-induced Smad2 phosphorylation, however enhancing the phosphorylation of ERK, c-Jun N-terminal kinase (JNK), and p38 in TGF-β-treated Hep3B cells. Other PPAR ligands like the PPARγ agonist, troglitazone; the PPARα agonist, Wy-14643, and bezafibrate were also able to inhibit TGF-β-induced CTGF. The results suggest that 15d-PGJ₂ inhibits TGF-β-induced CTGF expression by inhibiting the phosphorylation of Smad2, which is independent of PPAR, and 15d-PGJ₂ might also act through a PPAR-dependent mechanism in human hepatoma cells. 15d-PGJ₂ might have a beneficent effect on prevention of liver fibrosis induced by environmental toxicants.     

Acute and sublethal effects of organophosphate insecticide chlorpyrifos on freshwater fish Oreochromis niloticus

Chlorpyrifos is a widely used organosphosphate insecticide in India. Residue of the insecticide is frequently detected in trace to moderate concentration in food grains and in surface water of different freshwater ecosystems of the country. In this study, 96?h LC₅₀ of the technical grade (94% a.i.) and commercial formulation (20% EC) of chlorpyrifos to freshwater fish Oreochromis niloticus were determined as 90.0 and 42.0?µg/L based on 2?h actual concentration of chlorpyrifos in water. About 96?h exposure to sublethal concentrations (0, 12.0 and 25.0?μg/L) of the commercial formulation (20% EC) of chlorpyrifos reduced the level of hepatic glycogen, activities of alkaline phosphatase, acetylcholinesterase, and catalase in liver and elevated the level of plasma glucose and activities of hepatic acid phosphatase, aspartate aminotransferase, and alanine aminotransferase in O. niloticus. About 28-day exposure to these sub-lethal concentrations caused anemia in fish, while 90 days exposure reduced growth of the fish and carcass concentration of crude protein and crude lipid as compared to control. It was concluded from this study that commercial formulation of chlorpyrifos (20% EC) was highly toxic to O. niloticus. Exposure to sub-lethal concentrations of the insecticide could induce oxidative stress and anemia resulting in reduced growth of the fish.     

糖尿病视网膜病变患者血清和玻璃体液中细胞因子的相关性研究

目的筛选出较为可靠的细胞因子作为增殖性糖尿病视网膜病变患者的临床检测指标。方法对23例增殖性糖尿病视网膜病变患者和24例新鲜的孔源性视网膜脱离患者外周血和玻璃体液中转化生长因子β2（TGF—β2）,白细胞介素8（IL-8）,以及血管内皮生长因子（VEGF）的含量进行检测,并进行统计学分析。结果增殖性糖尿病视网膜病变患者（试验组）的玻璃体液中的VEGF和IL-8浓度与对照组相比均明显增高,而TGF．B：浓度明显低于对照组[试验组TGF-β2、IL-8、VEGF水平分别为（69．53±2．94）、（95．23±6．55）、（45．39±4．86）μg／L,对照组分别为（87．32±3．21）、（77．42±5．03）、（37．784-2．09）μg／L,P〈0．01或P〈0．05]。试验组外周静脉血中IL-8浓度（94．91±7．37）μg／L,高于对照组的（77．42±5．03）μg／L。只有玻璃体与血清中IL-8呈明显正相关（r=0．9522,P〈0．01）。结论IL-8有可能成为增殖性糖尿病视网膜病变患者临床检测指标之一。     

IL-1β对人鼻黏膜上皮细胞黏蛋白MUC5AC mRNA的表达的影响

目的探讨IL-1β对鼻黏膜上皮细胞黏蛋白MUC5ACmRNA表达的影响。方法在培养的第二代人鼻黏膜上皮细胞加入IL-1β(10ng/ml)刺激24h后,采用荧光定量巢式RT-PCR检测人鼻黏膜上皮细胞中MUC5ACmRNA的定量表达。结果在培养的鼻黏膜上皮细胞上检测到MUC5ACmRNA的表达,IL-1β刺激组MUC5ACmRNA定量表达[(4.60±1.89)108拷贝/μg]均高于对照组[(2.50±1.40)107拷贝/μg],差异具有统计学意义(P<0.05﹚。结论 IL-1β诱导鼻黏膜上皮细胞中MUC5ACmRNA的表达增高,提示IL-1β可能具有上调鼻黏膜上皮细胞黏蛋白mRNA的表达的作用。     

探究哮喘患者血清IL-13、VEGF、TGF-β1与气道炎症反应的相关性

目的 探究与分析哮喘患者血清白介素-13 (IL-13)、血管内皮生长因子(VEGF)、转化生长因子-β1 (TGF-β 1)与气道炎症反应的相关性.方法 选取本院自2013年8月至2015年8月收治的80例哮喘患者,按照急性发作期与临床缓解期分为观察A组与观察B组,每组各40例,另选择同时收治的健康体检人员40例作为对照组,测量三组人员的血清IL-13、VEGF、TGF-β 1,并给予肺功能检查,对结果行统计学分析.结果 观察B组与观察A组相比IL-13、VEGF、TGF-β 1均较低,FEV1及FEV1/FVC均较高,差异具有统计学意义(P＜0.05).对照组与观察B组相比IL-13、VEGF、TGF-β 1均较低,FEV1及FEV1/FVC均较高,差异具有统计学意义(P＜0.05).血清IL-13、VEGF、TGF-β 1水平互相呈正相关性,即三者若其中一项升高,另外两项也随之升高(P＜0.05).血清IL-13、VEGF、TGF-β 1水平与FEV1及FEV 1/FVC分别均呈负相关性,即血清IL-13、VEGF、TGF-β 1水平升高时,FEV1及FEV 1/FVC降低(P＜0.05).结论 哮喘患者血清IL-13、VEGF、TGF-β 1与气道炎症反应具有一定的相关性,为临床治疗与诊断提供重要基础.