Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model

Background and Purpose

Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice.

Experimental Approach

Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg^–1 per mice) or dexamethasone (5 mg kg^–1 per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-α, IFN-γ and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry.

Key Results

We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation.

Conclusions and Implications

These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.     

熊果酸对动脉粥样硬化大鼠氧化应激和炎性反应的影响

目的 研究熊果酸(UA)对动脉粥样硬化(AS)大鼠氧化应激和炎性反应的抑制作用,并探讨其机制.方法 采用高脂饲料喂养结合腹腔注射VD3的方法建立早期AS大鼠模型,并分别灌胃给予UA(10、20、40 mg· kg-1· d-1)和辛伐他汀(SV, 1.8 mg· kg-1· d-1)进行干预,作为干预组,另设模型组和健康对照组(喂食正常饲料并腹腔注射生理盐水).采用比色法测定血清中抗氧化酶[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)]活性和丙二醛(MDA)、活性氧簇(ROS)含量;酶联免疫法(ELISA)测定血浆中炎性细胞因子[C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)]含量;苏木精-尹红(HE)染色观察主动脉形态结构改变并进行病变分级.结果 UA(20、40 mg· kg -1· d-1)同步干预组大鼠血清中 SOD、CAT 活性较模型组显著升高[(318.3 ±29.4)、(12.3 ±2.4)U· mL-1vs(249.3 ±25.1)、(9.3 ±1.7)U· mL-1],MDA、ROS含量显著降低[(31.2 ±5.1)vs(49.6 ±7.0) mmol· L-1和(291.3 ±31.8)vs(402.9 ±35.7)U· mL-1],且UA 40 mg· kg -1· d-1干预组GSH-Px活性显著升高[(809.3 ± 58.4)vs(676.1 ±48.5)U· mL-1];UA(20、40 mg· kg-1· d-1)同步干预组大鼠血浆中CRP、TNF-α、IL-1β、IL-6含量较模型组均显著降低,且UA 40 mg· kg-1· d-1干预组IL-10含量显著升高[(37.6 ±4.9)vs(23.9 ±3.2)ng· L-1];UA同步干预组大鼠主动脉形态结构改变较模型组明显改善、病变评分显著降低,其中以UA 40 mg· kg-1· d-1干预组效果最为显著.结论UA可能通过抑制氧化应激损伤和炎性反应而对AS大鼠起到一定保护作用.     

Artesunate suppresses inflammation and oxidative stress in a rat model of colorectal cancer

Anti-inflammatory drugs are well known to reduce the risk of colon cancer and prophylactic use of such agents is gaining acceptance as a cancer prevention therapy. As artesunate, an antimalarial drug, has been shown to exhibit chemopreventive properties, the present study was carried out to evaluate its inhibitory effect on oxidative stress and inflammation in a rat model of colon carcinogenesis. A chemical carcinogen, 1,2-dimethylhydrazine was injected twice at an interval of 1 week to induce preneoplastic lesions in the colon and the parameters indicating oxidative stress and inflammation were evaluated after 8 weeks. Artesunate (50 and 150 mg/kg) and aspirin (60 mg/kg) were administered orally throughout the study. Analysis of colon tissue revealed that both the drugs preserved histoarchitecture, inhibited cellular influx, decreased the levels of oxidative stress and inflammatory markers, downregulated cyclooxygenase-2, inducible nitric oxide synthase, nuclear factor κB, and interleukin 1β in comparison to the experimental control. Suppression of oxidative stress and pro-inflammatory signaling by both the drugs were found to contribute to inhibition of colon carcinogenesis. The protection afforded by these drugs was found to be comparable. Our study shows that like aspirin, use of artesunate could also reduce the risk of colon cancer and it has a potential for further evaluation for the treatment purpose.     

Microminipig, a non-rodent experimental animal optimized for life science research:novel atherosclerosis model induced by high fat and cholesterol diet

Atherosclerotic lesions were observed in male and ovariectomized female Microminipig (MMP) fed a high fat and cholesterol diet with sodium cholate (HFCD/SC) for 3 months. HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol ester (CE). Unlike the mouse or rabbit, a dominant LDL-C fraction in the intact MMP, similar to that in humans, was observed by serum lipoprotein analysis. HFCD/SC increased body weight gain. At the end of the experiment, computed tomography scans of conscious animals showed that HFCD/SC had decreased liver attenuation values (Hounsfield unit) and increased subcutaneous and abdominal fat, suggesting the induction of fatty liver and obesity. HFCD/SC induced atherosclerotic lesions in systemic arteries, including the external and internal iliac arteries, abdominal aorta, coronary artery, and cerebral arterial circle. Atherosclerosis and pathological findings induced by HFCD/SC in MMP were similar to those in humans. The MMP is a potentially suitable tool for investigating human atherosclerosis.     

Effect of high fluoride and high fat on serum lipid levels and oxidative stress in rabbits

The purpose of this study was to explore the effects of high fluoride and high fat on triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) in rabbits. A factorial experimental design was used, with two factors (fluoride and fat) and three levels. Seventy-two male rabbits were randomly assigned into nine groups according to initial weight and serum lipid levels. The rabbits were fed with basic feed, moderate fat feed or high fat feed and drank tap water, fluoridated water at levels of 50 and 100 mg fluorion/L freely. Biological materials were collected after 5 months, and serum lipid, T-AOC, LPO, and MDA levels were then measured. Using these data, the separate and interactive effects of high fluoride and high fat were analyzed. High fluoride and high fat both increased serum levels of TC, HDL-C and LDL-C significantly (P < 0.05), and there was also a synergistic effect between high fluoride and high fat (P < 0.05). High fluoride and high fat had different effects on TG levels: high fat significantly increased TG levels (P < 0.01) whereas high fluoride had nothing to do with TG levels (P > 0.05). High fat significantly elevated LPO and MDA levels and lowered T-AOC levels in serum (P < 0.05). Similarly, high fluoride significantly increased LPO and MDA levels in serum (P < 0.05). However, there was no interactive effect between high fat and high fluoride on these indexes. In summary, high fluoride and high fat increased serum TC and LDL-C levels individually and synergistically, and this would cause and aggravate hypercholesterolemia in rabbits. At the same time, high fluoride and high fat both made the accumulation of product of oxidative stress in experimental animals.     

Vitamin C protects rat cerebellum and encephalon from oxidative stress following exposure to radiofrequency wave generated by a BTS antenna model

Radio frequency wave (RFW) generated by base transceiver station has been reported to produce deleterious effects on the central nervous system function, possibly through oxidative stress. This study was conducted to evaluate the effect of RFW-induced oxidative stress in the cerebellum and encephalon and the prophylactic effect of vitamin C on theses tissues by measuring the antioxidant enzymes activity, including: glutathione peroxidase, superoxide dismutase, catalase, and malondialdehyde (MDA). Thirty-two adult male Sprague-Dawley rats were randomly divided into four equal groups. The control group; the control-vitamin C group received L-ascorbic acid (200?mg/kg of body weight/day by gavage) for 45 days. The RFW group was exposed to RFW and the RFW+ vitamin C group was exposed to RFW and received vitamin C. At the end of the experiment, all groups were killed and encephalon and cerebellum of all rats were removed and stored at ?70?°C for measurement of antioxidant enzymes activity and MDA. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p?p?相似文献   

Evaluation of the toxicology,anti-lipase,and antioxidant effects of Callistemon citrinus in rats fed with a high fat-fructose diet

ContextCallistemon citrinus Skeels (Myrtaceae) exhibits many biological activities.ObjectiveThis study analyzes for the first time, the toxicity, obesogenic, and antioxidant effects of C. citrinus in rats fed with a high fat-fructose diet (HFFD).Materials and methodsFour studies using male Wistar rats were conducted: (a) 7 groups (n = 3): control (corn oil) and ethanol extract of C. citrinus leaf (single oral dose at 100–4000 mg/kg) for acute toxicity; (b) 2 groups (n = 8): control (corn oil) and C. citrinus (1000 mg/kg/day) for 28 days for subacute toxicity; (c) 3 groups (n = 4) with single oral dose of lipid emulsion: control (lipid emulsion), C. citrinus and orlistat (250 and 50 mg/kg, respectively) for lipid absorption; (d) 4 groups (n = 6): control (normal diet) and 3 groups fed with HFFD: HFFD only, C. citrinus and simvastatin (oral dose 250 and 3 mg/kg, respectively) for 13 weeks. Antioxidant enzymes and biomarkers were evaluated and inhibition of pancreatic lipase was determined in vitro.ResultsToxicological studies of C. citrinus showed no differences in biochemical parameters and lethal dose (LD₅₀) was higher than 4000 mg/kg. C. citrinus inhibited pancreatic lipase activity, with IC₅₀ of 392.00 µg/mL, and decreased lipid absorption by 70%. Additionally, it reduced the body weight 22%, restored the activities of antioxidant enzymes, and reduced the biomarkers of oxidative stress.ConclusionsCallistemon citrinus showed an effect against oxidative stress by reducing biomarkers and induced antioxidant system, without toxic effects.     

Urtica dioica attenuates ovalbumin-induced inflammation and lipid peroxidation of lung tissues in rat asthma model

Context: To find bioactive medicinal herbs exerting anti-asthmatic activity, we investigated the effect of an aqueous extract of Urtica dioica L. (Urticaceae) leaves (UD), the closest extract to the Algerian traditional use.

Objective: In this study, we investigated the in vivo anti-asthmatic and antioxidant activities of nettle extract.

Materials and methods: Adult male Wistar rats were divided into four groups: Group I: negative control; group II: Ovalbumin sensitized/challenged rats (positive control); group III: received UD extract (1.5?g/kg/day) orally along the experimental protocol; group IV: received UD extract (1.5?g/kg/day) orally along the experimental protocol and sensitized/challenged with ovalbumin. After 25?days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. The oxidative stress parameters were evaluated in the lungs, liver and erythrocytes. Then, correlations between markers of airway inflammation and markers of oxidative stress were explored.

Results: UD extract significantly (p?p?50 value.

Conclusions: The results confirmed that UD administration might be responsible for the protective effects of this extract against airway inflammation.     

Hydroalcoholic extract of Emblica officinalis protects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant,anti-inflammatory,and neuroprotective intervention

Context: Emblica officinalis (Euphorbiaceae), commonly known as amla, is traditionally used for central nervous system (CNS) disorders.

Objective: In the present study, the effect of standardized hydroalcoholic extract of E. officinalis fruit (HAEEO), an Indian medicinal plant with potent antioxidant activity, was studied against kainic acid (KA)-induced seizures, cognitive deficits and on markers of oxidative stress.

Materials and methods: Rats were administered KA (10?mg/kg, i.p.) and observed for behavioral changes, incidence, and latency of convulsions over 4?h. The rats were thereafter sacrificed for estimation of oxidative stress parameters: thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH). The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was also determined in the rat brain.

Results: Pretreatment with HAEEO (500 and 700?mg/kg, i.p.) significantly (P?<?0.001) increased the latency of seizures as compared with the vehicle-treated KA group. HAEEO significantly prevented the increase in TBARS levels and ameliorated the fall in GSH. Furthermore, HAEEO dose-dependently attenuated the KA-induced increase in the TNF-α level in the brain. HAEEO also significantly improved the cognitive deficit induced by KA, as evidenced by increased latency in passive avoidance task.

Discussion and conclusion: HAEEO at the dose of 700?mg/kg, i.p., was most effective in suppressing KA-induced seizures, cognitive decline, and oxidative stress in the brain. These neuroprotective effects may be due to the antioxidant and anti-inflammatory effects of HAEEO.     

Thinner inhalation effects on oxidative stress and DNA repair in a rat model of abuse

Humans can come into contact with thinner by occupational exposure or by intentional inhalation abuse. Numerous studies of workers for genotoxic effects of thinner exposure have yielded conflicting results, perhaps because co‐exposure to variable other compounds cannot be avoided in workplace exposure studies. In contrast, there is no data concerning the genotoxic effects of intentional inhalation abuse. The aim of this project was to examine the genotoxic effects of thinner inhalation in an animal model of thinner abuse (rats exposed to 3000 ppm toluene, a high solvent concentration over a very short, 15 min time period, twice a day for 6 weeks). The data presented here provides evidence that thinner inhalation in our experimental conditions is able to induce weight loss, lung abnormalities and oxidative stress. This oxidative stress induces oxidative DNA damage that is not a characteristic feature of genotoxic damage. No significant difference in DNA damage and DNA repair (biomarkers of genotoxicity) in lymphocytes from thinner‐treated and control rats was found. Lead treatment was used as a positive control in these assays. Finally, bone marrow was evaluated as a biomarker of cellular alteration associated with thinner inhalation. The observed absence of hemopoietic and genetic toxicity could be explained in part by the absence of benzene, the only carcinogenic component of thinner; however, benzene is no longer a common component of thinner. In conclusion, thinner did not cause genotoxic effects in an experimental model of intentional abuse despite the fact that thinner inhalation induces oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd.     

Immunosuppression and oxidative stress induced by subchronic exposure to carbosulfan in rat spleen: immunomodulatory and antioxidant role of N-acetylcysteine

The present study was designed to determine the immunosuppressive effects of carbosulfan (CB) and their relationship with an increased formation of reactive oxygen species in rat. Further, we aimed to evaluate the protective effects of N-acetyl-cysteine (NAC) against immunopathological changes induced by CB. Carbosulfan (25?mg/kg) and NAC (2?g/l) were given daily to rats during 30 days, via oral gavage and drinking water, respectively. Cell-mediated immune function, cytokines production, biomarkers of cell redox state maintenance, lipid peroxidation and the activities of antioxidant enzymes were measured in the spleen. Our data showed an increase in WBC percent (28.42%), a reduction in spleen CD8 T-lymphocytes (?85.63%) and a decrease in immunosuppressive cytokines production such as INF-gamma and IL-4. There was a switch from Th1-type to Th2-type cytokines with an unbalance toward anti-inflammatory cytokines. Moreover, a significant decrease in reduced glutathione (?71.68%) and total thiols (?39.81%) levels were observed in treated rats. Conversely, malondialdehyde level in spleen was increased (?42.3%), while glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase activities were depleted. Our results suggest that subchronic CB administration affects cellular enzyme and non-enzyme-mediated antioxidant defense systems and promotes immunotoxicity in rat. On the other hand, our data showed protective effects of NAC. Indeed, there was a recovery of oxidative stress markers and cytokines production. The use of NAC, in our study, as a therapeutic agent showed interesting results against CB toxicity.     

血清胆红素和氧化修饰低密度脂蛋白水平与冠心病患者冠状动脉病变程度关系研究

目的探讨血清胆红素（BIL）与氧化修饰低密度脂蛋白（OX-LDL）水平和冠状动脉粥样硬化性心脏病（CHD）患者冠状动脉病变间的关系及其临床意义。方法160例患者按冠状动脉造影结果分为CHD组和非CHD组,采用Gensini法计算冠状动脉病变积分（CSS）。检测空腹血清总胆红素（TBIL）、直接胆红素（DBIL）、间接胆红素（IBIL）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）浓度,氧化修饰低密度脂蛋白（OX-LDL）水平。结果CHD组血清TBL明显低于非CHD组[（7.9±2.7）μmol/Lvs（15.5±3.9）μmol/L,P〈0.01],而血浆OX-LDL明显高于非CHD组[（98±38）mmol/Lvs（29±11）μmol/L,P〈0.01]。相关分析显示血清TBIL与血浆OX-LDL的变化呈负相关（r=-0.65,P〈0.01）。双变量分析显示TBIL、DBIL、IBIL与CSS呈负相关（P〈0.05或〈0.01）结论血清胆红素代谢紊乱参与了CHD的发生和发展,其水平变化与冠状动脉病变的严重性有关。CHD患者血清TBIL抗LDL氧化能力的减弱可能是导致OX-LDL升高的重要原因。     

Pioglitazone improves lipid and insulin levels in overweight rats on a high cholesterol and fructose diet by decreasing hepatic inflammation

Background and purpose:

Nutrient overload leads to obesity and insulin resistance. Pioglitazone, a selective peroxisome proliferator-activated receptor (PPAR)γ agonist, is currently used to manage insulin resistance, but the specific molecular mechanisms activated by PPARγ are not yet fully understood. Recent studies suggest the involvement of suppressor of cytokine signalling (SOCS)-3 in the pathogenesis of insulin resistance. This study aimed to investigate the hepatic signalling pathway activated by PPARγ activation in a non-genetic insulin-resistant animal model.

Experimental approach:

Male Wistar rats were maintained on a high-cholesterol fructose (HCF) diet for 15 weeks. Pioglitazone (3 mg·kg⁻¹) was administered orally for the last 4 weeks of this diet. At the end of the treatment, serum was collected for biochemical analysis. Levels of PPARγ, SOCS-3, pro-inflammatory markers, insulin receptor substrate-2 and Akt/glycogen synthase kinase-3β phosphorylation were assesed in rat liver.

Key results:

Rats fed the HCF diet exhibited hyperlipidemia, hyperinsulinemia, impaired glucose tolerance and insulin resistance. Pioglitazone administration evoked a significant improvement in lipid metabolism and insulin responsiveness. This was accompanied by reduced hepatic expression of SOCS-3, interleukin-6, tumour necrosis factor-α and markers of neutrophil infiltration. Diet-induced PPARγ expression was unaffected by the pioglitazone treatment.

Conclusion and implications:

Chronic pioglitazone administration reduced hepatic inflammatory responses in rats fed a HCF diet. These effects were associated with changes in hepatic expression of SOCS-3, which may be a crucial link between the reduced local inflammation and the improved insulin signalling.This article is commented on by Chatterjee, pp. 1889–1891 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00739.x     

Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury

Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. Previous studies showed that ozone oxidative preconditioning (OzoneOP) attenuated renal ischemia/reperfusion injury. The objective of this study was to examine the role of the OzoneOP in modulating inflammation and apoptosis after renal ischemia/reperfusion injury. Rats were subjected to 45 min of renal ischemia, with or without treatment with OzoneOP (1 mg/kg). Renal function, inflammation and apoptosis were compared at 24 h after renal injury. OzoneOP improved the renal dysfunction and reduced inflammation and apoptosis after ischemia/reperfusion injury. In conclusion, OzoneOP has potent anti-apoptotic and anti-inflammatory properties. These findings may have major implications in the treatment of human ischemic acute renal failure.     

Exendin-4 protects the hearts of rats from ischaemia/reperfusion injury by boosting antioxidant levels and inhibition of JNK/p66Shc/NADPH axis

Exendin-4, a glucagon-like peptide-1 receptor agonist, was shown to protect against cardiac ischaemia/reperfusion (I/R) injury by suppressing oxidative stress. p⁶⁶Shc, a pro-oxidant and an apoptotic protein, is activated in the infarcted left ventricles (LVs) after induction of I/R. This study investigated if the cardiac protective effect of Exendin-4 against I/R injury in rats involves inhibition of p⁶⁶Shc and to determine the underlying mechanisms behind this. Adult male rats (n = 12/group) were divided into four groups as a sham, a sham + Exendin-4, an I/R, and an I/R + Exendin-4. Exendin-4 was administered to rats 7 days before the induction of I/R. Ischaemia was induced by ligating the left anterior descending (LAD) coronary artery for 40 minutes followed by reperfusion for 10 minutes. The infarct myocardium was used for further analysis. Exendin-4 significantly reduced infarct area (by 62%), preserved LV function and lowered serum levels of LDH and CK-MB in I/R-induced rats. Also, it significantly reduced LV levels of ROS and MDA and protein levels of cytochrome-c and cleaved caspase-3 but significantly increased levels of glutathione (GSH) and manganese superoxide dismutase (MnSOD) in LVs of I/R rats indicating antioxidant and anti-apoptotic effects. Furthermore, it inhibited JNK and p⁶⁶Shc activation and downregulated protein levels of p⁶⁶Shc and NADPH oxidase with no effect on protein levels/activity of p53 and PKCβII. Of note, Exendin-4 also increased GSH and MnSOD in LVs of control rats. In conclusion, Exendin-4 cardioprotective effect in I/R hearts is mediated mainly by antioxidant effect and inhibition of JNK/P⁶⁶Shc/NADPH oxidase.     

白头翁皂苷B4对高脂饮食诱导ApoE-/-小鼠动脉粥样硬化的治疗作用及机制研究

目的 研究白头翁皂苷B₄的抗动脉粥样硬化作用及其机制。方法 将雄性的C57小鼠设为对照组,共6只,给予正常饮食;给予 ApoE^-/-小鼠高脂饮食喂养 9周后,随机分为 4组：模型组、辛伐他汀（阳性对照,5 mg·kg^-1）组及白头翁皂苷 B₄低、高剂量（5、20 mg·kg^-1）组,每组7只。ig给药9周,C57对照组和ApoE^-/-模型组给予等量的0.9%的氯化钠溶液。给药的同时造模小鼠仍给予高脂饮食,每周统计 1次体质量,给药 9周后进行取材。通过兽用血常规分析仪检测全血中血小板（PLT）、白细胞（WBC）、中性粒细胞（Neu）及淋巴细胞（Lym）水平;ELISA法检测血清中白细胞介素-6（IL-6）的水平;试剂盒法检测血清中总胆固醇（TC）、游离胆固醇（FC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平;通过全长主动脉油红染色检测主动脉中脂质积累情况;通过苏木精-伊红染色法、Masson染色法和油红O染色法检测主动脉窦的组织病理变化。结果 与模型组比较,在白头翁皂苷B₄及辛伐他汀给药后,体质量呈降低趋势;PLT、WBC、Neu、Lym、IL-6水平均显著降低（P＜0.05、0.01、0.001）;血清TC、FC、TG、LDL-C水平显著降低（P＜0.001）,HDL-C水平显著升高（P＜0.001）;全长主动脉被染红区域显著缩小（P＜0.001）;主动脉窦油红染色区域面积明显减少,小鼠主动脉窦斑块减少,可见少量泡沫细胞,炎症细胞浸润减少,中膜层平滑肌及弹性纤维排列增厚不明显,胶原含量多且分布规律,胶原间的腔隙减少,油红染色区域面积明显减少。结论 白头翁皂苷B₄对高脂饮食诱导的ApoE^-/-基因敲除小鼠动脉粥样硬化具有治疗作用,其作用机制与减少脂质浸润和炎症反应有关。     

花刺参黏多糖对胎牛血清诱导的血管平滑肌细胞增殖和凋亡的影响

目的观察花刺参黏多糖对10%胎牛血清(FBS)诱导的大鼠血管平滑肌细胞增殖和凋亡的影响,以探讨花刺参黏多糖抗动脉粥样硬化、预防经皮腔内冠状动脉成形术后再狭窄的可能机制。方法组织块贴片法体外原代培养大鼠血管平滑肌细胞,细胞增殖采用MTT、流式细胞周期分析;流式细胞术、TUNEL实验方法观察细胞凋亡。结果10?S刺激可促进血管平滑肌细胞增殖、抑制其凋亡,而花刺参黏多糖(5~20g.L-1)有浓度依赖性地逆转作用,MTT吸光度(A值)由0.484±0.034减少到0.369±0.019(P<0.01),流式细胞分析示G0/G1期细胞比例由54.7±2.7%增加到75.8±1.8%(P<0.01);流式细胞分析示细胞凋亡率由2.84±1.44%增加到13.51±2.75%(P<0.01);TUNEL结果显示凋亡细胞比例由2.90±1.05%增加为8.60±1.13%(P<0.01)。结论花刺参黏多糖可抑制10?S诱导的血管平滑肌细胞增殖,促进其细胞凋亡,这可能对延缓动脉粥样硬化发生发展以及预防经皮腔内冠状动脉成形术后再狭窄发生起到一定作用。     

The kinetics of transcriptomic changes induced by cigarette smoke in rat lungs reveals a specific program of defense, inflammation, and circadian clock gene expression.

Gene expression profiling in animal models exposed to cigarette mainstream smoke (CS) shapes up as a promising tool for investigating the molecular mechanisms involved in the onset and development of CS-related disease and may aid in the identification of disease candidate genes. Here we report on differential gene expression in lungs of rats exposed for 2, 7, and 13 weeks to 300 and 600 microg total particulate matter/l CS with sacrifice 2, 6, or 20 h after the last exposure. Regarding antioxidant and xenobiotic-metabolizing (phase I/II) enzymes, a stereotypic, mostly transient, expression pattern of differentially expressed genes was observed after each exposure period. The expression patterns were generally dose dependent for antioxidant and phase II genes and not dose dependent for phase I genes at the CS concentrations tested. However, with increasing length of exposure, there was a distinct, mostly sustained and dose-sensitive, expression of genes implicated in innate and adaptive immune responses, clearly pointing to an emerging inflammatory response. Notably, this inflammatory response included the expression of lung disease-related genes not yet linked to CS exposure, such as galectin-3, arginase 1, and chitinase, as well as genes encoding proteolytic enzymes. Finally, our experiments also revealed a CS exposure-dependent shift in the cyclical expression of genes involved in controlling the circadian rhythm. Altogether, these results provide further insight into the molecular mechanisms of CS-dependent disease onset and development and thus may also be useful for defining CS-specific molecular biomarkers of disease.