Protective effects of escin against indomethacin-induced gastric ulcer in mice

Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18?mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8?mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6?h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-α, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-α, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect.     

Escin attenuates cerebral edema induced by acute omethoate poisoning

Organophosphorus exposure affects different organs such as skeletal muscles, the gastrointestinal tract, liver, lung, and brain. The present experiment aimed to evaluate the effect of escin on cerebral edema induced by acute omethoate poisoning. Sprague-Dawley rats were administered subcutaneously with omethoate at a single dose of 60 mg/kg followed by escin treatment. The results showed that escin reduced the brain water content and the amount of Evans blue in omethoate-poisoned animals. Treatment with escin decreased the levels of tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and prostaglandin E? (PGE?) in the brain. Escin also alleviated the histopathological change induced by acute omethoate poisoning. The findings demonstrated that escin can attenuate cerebral edema induced by acute omethoate poisoning, and the underlying mechanism was associated with ameliorating the permeability of the blood-brain barrier.     

Escin attenuates acute lung injury induced by endotoxin in mice

Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and antiedematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-α, and IL-1β, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity.     

Escin attenuates cerebral edema induced by acute omethoate poisoning

Organophosphorus exposure affects different organs such as skeletal muscles, the gastrointestinal tract, liver, lung, and brain. The present experiment aimed to evaluate the effect of escin on cerebral edema induced by acute omethoate poisoning. Sprague-Dawley rats were administered subcutaneously with omethoate at a single dose of 60?mg/kg followed by escin treatment. The results showed that escin reduced the brain water content and the amount of Evans blue in omethoate-poisoned animals. Treatment with escin decreased the levels of tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂) in the brain. Escin also alleviated the histopathological change induced by acute omethoate poisoning. The findings demonstrated that escin can attenuate cerebral edema induced by acute omethoate poisoning, and the underlying mechanism was associated with ameliorating the permeability of the blood–brain barrier.     

七叶皂苷钠对肺部急性炎性渗出的影响

目的：研究七叶皂苷钠对肺部急性炎性渗出的作用。方法：以乙酸所致的腹腔毛细血管通透性增高模型小鼠观察七叶皂苷钠对急性渗出作用的时效关系;以肾上腺素致大鼠急性肺水肿和内毒素致小鼠急性肺损伤模型,观察七叶皂苷钠对急性肺部炎症渗出的影响。结果：七叶皂苷钠抑制急性炎症渗出作用的起效较慢,给药5h后作用开始较为明显,作用可持续24h;预防给药,可明显降低急性肺水肿大鼠的死亡率;对肾上腺素及内毒素所致肺部炎症也有明显抑制作用。结论：七叶皂苷钠可用于急性肺炎中肺部急性炎症渗出的防治。     

Escin enhances anti-rheumatoid arthritis effects of low dose glucocorticoids through up-regulation of glucocorticoid receptor

OBJECTIVE To investigate the anti-rheumatoid arthritis(RA) effect of Escin combined with low dose of GCs(dexamethasone, Dex) and its underlying mechanism. METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro. In vivo experiment: rats were randomly divided into model group(AIA), dexamethasone high dose(Dex, 0.2 mg·kg~(-1)) group, dexamethasone low dose(Dex, 0.05 mg·kg~(-1))group, Escin 10 mg·kg~(-1) group, Dex 0.05+Escin group, 10 rats in each group, another 10 were used as normal control group. The vehicle and the corresponding drug were administered intragastrically(ig) daily for 14 d. In vitro experiment: LPS was used to stimulate RAW264.7 macrophages for inflammatory models, which were divided into control group, LPS group, Dex with high dose(50 nmol·L~(-1))group, and Dex with low dose(12.5 nmol·L~(-1)) group. In the Escin 10 μmol·L~(-1) group and the Dex+Escin(12.5 nmol·L~(-1)+10 μmol·L~(-1))group, the corresponding drugs were added to each well. After 2 h, LPS was added to induce inflammation. RESULTS Escin combined with low dose Dex significantly decreased arthritic index, serum IL-6 and TNF-α, improved paw swelling, and ameliorated the joint pathology immune organ pathology significantly. Gene chip results revealed that Nr3 c1(GR) altered significantly. And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro. Furthermore, Escin combined with low dose Dex also significant increase GR mRNA expression. However, when suppression of GR by its specific inhibitor, the anti-RA effect of Escin combined with low dose Dex was abolished. CONCLUSION Escin combined with Dex reduces the dose of Dex, and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex. This combination might be attributed to GR activation. This study might provide a new combination drugs for the treatment of RA.     

Isofraxidin exhibited anti-inflammatory effects in vivo and inhibited TNF-α production in LPS-induced mouse peritoneal macrophages in vitro via the MAPK pathway

Isofraxidin (IF) is a Coumarin compound that can be isolated from medicinal plants, such as Sarcandra glabra (Thunb.). Nakai is widely used in Asian countries for the treatment of anti-bacterial, anti-inflammatory and anti-tumour action. The present investigation was designed to evaluate the effect of IF on inflammation and nociception. In addition, we investigated a potential novel mechanism to explain the anti-inflammatory properties of IF. In vivo, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, LPS-induced mouse endotoxic shock, acetic acid-induced mice writhing and formalin-induced mouse pain models were used to evaluate the anti-inflammatory activity of IF. In vitro, we examined the effects of IF inhibition on TNF-α production and the regulation of ERK1/2 and p38 phosphorylation activity in LPS-induced mouse peritoneal macrophages. Our results demonstrated that IF can significantly decrease xylene-induced ear edema, carrageenan-induced paw edema, acetic acid-induced writhing and formalin-induced pain. Moreover, IF greatly inhibited the production of TNF-α in the serum of LPS-stimulated mice and peritoneal macrophages, and it decreased phospho-p38 and ERK1/2 protein expression in LPS-stimulated mouse peritoneal macrophages. Overall, our data suggest that IF possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1/2.     

传统中药白花蛇舌草的抗肿瘤活性研究(英文)

研究了传统中药白花蛇舌草的乙醇提取有效部位对S180小鼠模型的肿瘤生长抑制作用、免疫系统及小鼠生存天数的影响。该醇提部位能有效抑制S180小鼠的肿瘤生长,并延长荷瘤小鼠的生存天数。通过灌胃给药,醇提有效部位在10mg/kg的剂量下与阳性对照药物环磷酰胺(20mg/kg)相比,能够有效降低荷瘤小鼠体内的肿瘤大小与重量。对荷瘤小鼠的脾指数,胸腺指数及血常规参数研究表明,该醇提有效部位对荷瘤小鼠未见明显的毒副作用。总之,研究结果表明白花蛇舌草的醇提部位具有有效的抗肿瘤活性。     

Determination of escin content in androgenic embryos and hairy root culture of Aesculus hippocastanum

Escin, a group of chemically related triterpenic glycosides, is widely used in commercial preparations for the treatment of venous insufficiency. Since the zygotic embryo cotyledons accumulate the highest amount of escin, it is currently extracted from the seeds of horse chestnut, Aesculus hippocastanum L. (Hippocastanaceae), on a large scale. As this material is available during only short period of the year, we studied the possibility of using plant tissue culture to obtain escin. For this purpose, the content of escin in androgenic embryos and hairy root cultures of horse chestnut was studied. Escin content was found to be dependent on the stage of androgenic embryo development and the type of phytoregulator supplemented to the nutritive medium. In the absence of phytoregulators, androgenic embryos at the globular stage of development contained approximately four times less escin than those at the cotyledonary stage. Inclusion of various phytoregulators in the nutritive media stimulated escin production. Among them, 2,4-dichlorophenoxyacetic acid (2,4-D) showed the most pronounced effect, with escin content almost reaching that found in zygotic embryos (6.77% versus 6.96%). Two hairy root clones produced substantial amounts of escin (3.57% and 4.09%), less than zygotic embryos, but higher than cotyledonary embryos on phytoregulator-free medium.     

On the pharmacodynamics of alpha- and beta-escin after oral application (author's transl)]

Contrary to the almost water insoluble crystalline beta-escinic acid, the water soluble forms of escin -- such as alpha-escinic acid or its salts, Na-b-escinate and the amorphous beta-escinic acid -- are so well absorbed by the gastro-intestinal tract that the effects after oral application could be compared with those of the reference substances furosemide, hydrocortisone, acetylsalicylic acid, azapropazone and phenylbutazone. Escin was tested in the stasis edema, cotton-pellet-granuloma, and UV-erythema, i.e., in test models which seem specially suited to characterize the properties of this substance. In these tests which reflect both the prophylactic and the therapeutic treatment escin has proven antiexudative-antiphlogistic effects. They are based on a favorable influence of permeability and diuresis.     

Endothelium protectant and contractile effects of the antivaricose principle escin in rat aorta

The triterpene saponin escin is the active component of the extract of seeds of Aesculus hippocastanum used in the treatment of chronic venous insufficiency. Escin is also used experimentally to increase membrane permeability in isolated cells. Since endothelial dysfunction is postulated to be involved in venous insufficiency, the possible endothelium-protectant effect of escin was explored in rat aortic rings, a model widely used to study such effects with cardiovascular agents. Escin enhanced endothelium-dependent relaxation induced by acetylcholine when such relaxation had been reduced by exposure to the superoxide ion generator pyrogallol. This effect was attributed to enhanced nitric oxide production by endothelial nitric oxide synthase, a calcium-dependent enzyme, activated by the increased endothelial cell permeability to calcium induced by escin. Another effect of escin thought to contribute to its therapeutic activity is its ability to produce venous contraction. The compound was found to induce concentration-related contraction also in rat aortic rings. This response was partially inhibited by removal of the endothelium or by preincubation with indomethacin, and was completely abolished by incubation in a calcium-free perfusion fluid. Contraction was considered to be due mainly to the aforementioned effect on calcium permeability, with some mediation by release of endothelial vasoconstrictor prostanoids. It was concluded that, in rat aorta, escin possesses an endothelium-protectant action and a direct contractile effect. The former could contribute to its beneficial effect in the treatment of venous insufficiency, while the latter could constitute a limiting side effect.     

清解方雾化吸入剂的抗炎作用研究

目的考察清解方雾化吸入剂的抗炎作用及其作用机制。方法采用二甲苯致小鼠耳廓肿胀实验、冰醋酸致小鼠毛细血管通透性增加实验以及角叉菜胶致小鼠足肿胀实验,观察清解方雾化吸入剂的抗炎作用。测定肿胀足部位炎症因子NO、PGE2、IL-1β和TNF-α,探讨其抗炎作用机制。结果清解方雾化吸入剂9.2、18.4 g/kg均能显著降低小鼠耳肿胀度(P0.05、0.01),降低灌洗液吸光度值(P0.05),抑制角叉菜胶引起的足跖肿胀(P0.05),显著抑制炎症部位炎症介质NO、PGE2水平(P0.01、0.001),显著抑制炎症部位细胞因子IL-1β、TNF-α的释放(P0.001),且清解方雾化吸入剂4.6 g/kg也显著抑制IL-1β的释放(P0.01)。结论清解方雾化吸入剂具有显著的抗炎作用,作用机制可能在于降低IL-1β、TNF-α致炎细胞因子的释放,减少炎症部位NO、PGE2炎症介质的生成。     

Soyasaponin Ab inhibits lipopolysaccharide-induced acute lung injury in mice

Soyasaponin Ab (SA) has been reported to have anti-inflammatory effect. However, the effects of SA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) have not been reported. The aim of this study was to investigate the anti-inflammatory effects of SA on LPS-induced ALI and clarify the possible mechanism. The mice were stimulated with LPS to induce ALI. SA was given 1 h after LPS treatment. 12 h later, lung tissues were collected to assess pathological changes and edema. Bronchoalveolar lavage fluid (BALF) was collected to assess inflammatory cytokines and nitric oxide (NO) production. In vitro, mice alveolar macrophages were used to investigate the anti-inflammatory mechanism of SA. Our results showed that SA attenuated LPS-induced lung pathological changes, edema, the expression of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lung tissues, as well as TNF-α, IL-6, IL-1β, and NO production in mice. Meanwhile, SA up-regulated the activities of superoxide dismutase (SOD) and catalase decreased by LPS in mice. SA also inhibited LPS-induced TNF-α, IL-6 and IL-1β production as well as NF-κB activation in alveolar macrophages. Furthermore, SA could activate Liver X Receptor Alpha (LXRα) and knockdown of LXRα by RNAi abrogated the anti-inflammatory effects of SA. In conclusion, the current study demonstrated that SA exhibited protective effects against LPS-induced acute lung injury and the possible mechanism was involved in activating LXRα, thereby inhibiting LPS-induced inflammatory response.     

泻心汤在急性炎症动物模型上的抗炎效应

目的研究泻心汤的抗炎效应及抗炎作用的机制。方法采用4种急性炎症模型,包括大鼠角叉菜胶及蛋清足肿胀、2%冰醋酸小鼠腹腔渗出和小鼠内毒素急性肺损伤模型,观察泻心汤对动物实验性急性炎症模型的影响;并观察小鼠内毒素急性肺损伤模型中,泻心汤对血浆一氧化氮合成酶、一氧化氮、肿瘤坏死因子-α及自由基产物丙二醛的影响。结果泻心汤ig给药后对上述4种炎症模型都具有良好的抗炎效果;并可以抑制内毒素炎症过程中诱生型一氧化氮合成酶的活性,抑制一氧化氮、肿瘤坏死因子-α等炎症因子的产生,减少自由基产物丙二醛生成。结论泻心汤具有良好的抗炎效应,且可以通过多途径产生抗炎作用。     

Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties

Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. It has a wide activity spectrum, reflecting on mechanisms of action that are not fully understood. The objectives of this work were to study the effects of VA on acute models of nociception and inflammation in rodents. VA (0.5, 1, 10, 25, and 50 mg/kg, p.o.) effects were evaluated on the carrageenan-induced paw edema, carrageenan-induced peritonitis, and plantar tests in rats, as well as by the formalin test in mice. The HE staining and immunohistochemistry assay for TNF-α in carrageenan-induced edema, from paws of untreated and VA-treated rats, were also carried out. VA decreased paw edema after carrageenan, and maximum effects were seen with doses equal to or higher than 10 mg/kg. VA also preserved the tissue architecture as assessed by the HE staining. Immunohistochemical studies revealed that VA significantly reduced TNF-α immunostaining in carrageenan-inflamed rat paws. In addition, the anti-inflammatory action of VA was potentiated by pentoxifylline (a phosphodiesterase inhibitor, known to inhibit TNF-α production), but not by sodium butyrate or by suberoylanilide hydroxamic acid (SAHA), nonspecific and specific inhibitors, respectively, of histone deacetylase. However, the decrease in the number of positive TNF-α cells in the rat paw was drastically potentiated in the VA?+?SAHA associated group. VA also reduced leukocytes and myeloperoxidase (MPO) releases to the peritoneal exudate, in the carrageenan-induced peritonitis. Although in the formalin test, VA inhibited both phases, the inhibition was mainly on the second phase. Furthermore, VA significantly increased the reaction time to thermal stimuli, as assessed by the plantar test. VA is a multi-target drug, presenting potent antinociceptive and anti-inflammatory properties at a lower dose range. These effects are partly dependent upon its inhibitory action on TNF-α-related pathways. However, the participation of the HDAC inhibition with the VA anti-inflammatory action cannot be ruled out. Inflammatory processes are associated with free radical damage and oxidative stress, and their blockade by VA could also explain the present results.     

Immunomodulatory effect of polysaccharides from submerged cultured Cordyceps gunnii

Context: The genus Cordyceps (Clavicipitaceae) is a group of entomopathogenic fungi that is widely used as tonic food or invigorant with broad-spectrum medicinal properties in China. Cordyceps gunnii (Berk.)Berk (C. gunnii), is also well known as the Chinese rare caterpillar fungus and has similar pharmacological activities with Cordyceps sinensis (C. sinensis). Polysaccharides (PS) from various Cordyceps species have demonstrated many interesting biological activities, including antitumor, immunopotentiation, hypoglycemic, and hypocholesterolemic activities. Objective: To investigate the effect of C. gunnii PS on the immunostimulatory antitumor function and expression of immune related cytokines in normal, immuno-suppressive, and H22-bearing mice, respectively. Methods: C. gunnii PS were extracted with hot water at 80°C for 2 h. Normal, immuno-suppressive, and H22-bearing mice were treated with PS respectively. By detecting the value of macrophage phagocytic index, proliferation of lymphocytes, natural killer (NK) cell activity and expression of related cytokines, interleukin (IL-4), tumor necrosis factor-α (TNF-a) and interferon-γ (IFN-γ), and tumor inhibition index in H22-bearing mice additionally, the effect of PS on immunostimulatory antitumor function and its mechanism were studied. Results: The total sugar content of the PS was determined to be 95% after purification. PS markedly increased the thymus and spleen indexes, the macrophage phagocytosis, the proliferation of splenic cells, and the level of IFN-γ and TNF-α. In tumor growth inhibition test, PS showed remarkable inhibition effects. Conclusion: PS from the C. gunnii could enhance nonspecific immunological function, humoral immunity, cellular immunity in mice, and inhibit tumor growth.     

Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway

Dexmedetomidine (Dex) is a highly selective α2-adrenergic receptor agonist that is widely used for sedation in intensive care units and in clinical anesthesia. Dex has also been shown to possess anti-inflammatory benefits. However, the underlying mechanism by which Dex relieves the inflammatory reaction in the lung tissues of septic mice has not been fully elucidated. In this study, we aimed to evaluate the protective effects and possible mechanism of Dex on the sepsis-induced lung inflammatory response in mice. Sepsis was induced in mice models through the intraperitoneal injection of lipopolysaccharide (LPS). The preemptive administration of Dex substantially abated sepsis-induced pulmonary edema, pulmonary histopathological changes, and NF-κB p65 activity. The production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both the mRNA and protein levels was also reduced. Moreover, these effects were significantly blocked by the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist α-bungarotoxin (α-Bgt). α-Bgt aggravated pulmonary edema and pulmonary histopathological changes, as well as increased NF-κB p65 activity and TNF-α and IL-6 expression at both the mRNA and protein levels. The overall results demonstrate that Dex inhibits the LPS-induced inflammatory reaction in the lung tissues of septic mice partly through the α7nAChR-dependent cholinergic anti-inflammatory pathway.     

Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-κB pathway

Naringin has been reported as an effective anti-inflammatory compound. We previously showed that naringin had antitussive effect on experimentally induced cough in guinea pigs. However, the effects and mechanism of naringin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice are not fully understood. In this study, our aim was to evaluate the anti-inflammatory activities of naringin on LPS-induced ALI in mice and clarify its underlying mechanisms of action. We found that in vivo pretreatment with naringin markedly decreased the lung wet weight to dry weight ratio, and led to significant attenuation of LPS-induced evident lung histopathological changes. Meanwhile, naringin significantly reduced bronchoalveolar lavage fluid (BALF) total cell and neutrophil (PMN) counts after LPS challenge. Furthermore, naringin inhibited myeloperoxidase (MPO: a marker enzyme of neutrophil granule) and inducible nitric oxide synthase (iNOS) activities in lung tissue and alleviated LPS-induced tumor neurosis factor-α (TNF-α) secretion in BALF in a dose-dependent manner. Additionally, Western blotting showed that naringin efficiently blunt NF-κB activation by inhibiting the degradation of I?B-α and the translocation of p65. Taken together, these results suggest that naringin shows anti-inflammatory effects through inhibiting lung edema, MPO and iNOS activities, TNF-α secretion and pulmonary neutrophil infiltration by blockade of NF-κB in LPS-induced ALI.     

玉郎伞多糖对肉瘤荷瘤小鼠的体内抗肿瘤作用

目的探讨玉郎伞多糖(YLSPS)对肉瘤荷瘤小鼠的体内抗肿瘤作用及其与环磷酰胺(CTX)联合用药的减毒增效作用。方法昆明小鼠皮下注射肉瘤细胞株S180构建肉瘤荷瘤小鼠动物模型。评价YLSPS不同剂量(0.15、0.30和0.60g·kg-1·d-1)对小鼠胸腺指数(TI)、脾指数(SI)、瘤重及抑瘤率的影响,检测肝组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)的含量。与YLSPS单独用药相比,评价YLSPS不同剂量(0.15、0.30和0.60g·kg-1·d-1)联合CTX(0.01g·kg-1·d-1)用药对小鼠瘤重的影响,检测联合用药对小鼠TI、SI及外周白细胞数的影响。结果YLSPS低、中、高剂量组的TI分别为:(31±s7)、(35±6)和(37±6)mg·g-1,SI分别为:(92±16)、(93±8)和(106±8)mg·g-1。与模型组相比,YLSPS中、高剂量组的TI和SI均显著增高(P<0.01)。YLSPS低、中、高剂量组的平均抑瘤率分别为39.7%、41.3%和52.6%。与模型组比较,YLSPS各剂量组的SOD的活性增高,MDA含量降低。YLSPS各剂量+CTX(0.01g·kg-1·d-1)组,q值在0.85～1.25之间,可明显升高CTX降低的TI、SI及外周血白细胞数。结论YLSPS对肉瘤荷瘤小鼠有明显的抗肿瘤作用,与CTX合用有增效和减毒作用。     

糖皮质激素及NAC对腺病毒E1A蛋白上调IL-8及ICAM-1的抑制作用

目的探讨腺病毒E1A蛋白在致炎因素TNF-α作用下对人肺腺癌细胞(A549)炎症因子IL-8和ICAM-1表达的影响以及地塞米松(DXM)和N-乙酰半胱氨酸(NAC)的干预作用。方法构建稳定表达E1A蛋白的A549细胞系(E1A+组)及对照质粒转染细胞系(E1A-组)。用TNF-α刺激、DXM以及NAC干预细胞,用ELISA检测炎症因子IL-8蛋白的表达,流式细胞术检测ICAM-1的表达。结果E1A+组在10μg.L-1的TNF-α作用前后细胞IL-8蛋白浓度分别为(48.49±0.27)ng.L-1和(22 841.75±12.92)ng.L-1,明显高于E1A-组作用前的(1.67±0.07)ng.L-1和作用后的(3 576.04±3.20)ng.L-1,两组相比差异有统计学意义(P<0.01)。与TNF-α单独作用组相比,DXM和NAC预作用细胞可明显降低TNF-α诱导下IL-8的高表达,差异有统计学意义(P<0.01)。E1A+组在10μg.L-1的TNF-α作用前后细胞ICAM-1蛋白浓度(荧光强度)分别为17.12±3.32和35.12±3.19,均高于E1A-组作用前0.59±0.09和作用后29.72±3.32,两组相比差异有统计学意义(P<0.01)。与TNF-α单独作用组相比,DXM和NAC预作用细胞可明显降低TNF-α诱导的ICAM-1的表达,差异有统计学意义(P<0.01)。结论 E1A蛋白能够增加TNF-α诱导下的IL-8和ICAM-1蛋白的表达。DXM和NAC能够明显拮抗TNF-α诱导下的IL-8和ICAM-1的蛋白表达,具有较强的抗炎作用。腺病毒E1A蛋白对NAC及DXM的抗炎作用无明显拮抗作用。