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地塞米松、噻庚啶和山莨菪碱对LPS诱导大鼠肝脏TNFα表达的影响 总被引:1,自引:0,他引:1
地塞米松(Dex)、噻庚啶(Cyp) 和山莨菪碱(Ani) 对脂多糖(LPS) 诱导的大鼠肝脏TNFα表达的影响。Wistar大鼠40 只, 静脉注射LPS(EcoliO111B4 5m g/kg) 后, 立即静脉给予Dex 5m g/kg、Cyp5m g/kg 或Am i10m g/kg,于LPS攻击后2h 取动物的肝脏,APAAP法进行TNFα免疫组织化学研究,North-ern 杂交分析TNFαm RNA 表达水平。结果发现LPS攻击后2h, 肝脏TNFαm RNA 表达水平显著增高, 肝脏枯否氏细胞胞浆内有大量的TNFα红染颗粒。Dex、Cyp 或Ani均能显著降低大鼠肝脏TNFαm RNA 水平和TNFα含量。结果表明Dex、Cyp 和Ani均显著抑制LPS诱导的TNFα基因表达, 可能有抗感染性休克作用。 相似文献
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肿瘤坏死因子介导病理性氧供应依赖性的实验研究 总被引:1,自引:0,他引:1
本研究采用抗肿瘤坏死因子单克隆抗体预先保护实验动物,用ELISA法测定血浆中肿瘤坏死因子(TNF)浓度,藉以考察TNF在内毒素诱导病理性氧供应依赖性(POSD)模型中是否起介导作用。结果表明,(1)TNF浓度内毒素组显著高于对照组,抗体保护组显著低于无关抗体组(P<0.01)。(2)在Vo_2-Do_2关系中,抗体保护组可清楚地分为依赖段和非依赖段两部分,其临界氧运输量和合并氧提取率分别为10.80±321ml·min ̄(-1)·kg ̄(-1)和0.690,而无关抗体组则只有依赖段,合并氧提取率为0.408,显著低于抗体保护组。从而证明,TNF在内毒素所致的POSD现象中起介导作用。 相似文献
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DDPH[1-(2.6-二甲基苯乙氧基)-2-(3.4二甲氧基苯乙胺基)丙烷盐酸盐]是南京药科大学合成的降压新化合物,也具有降低肺动脉高压和抑制肺动脉平滑肌细胞增殖作用。本实验用细胞培养、免疫细胞化学、图像分析、3H-TdR、细胞周期测定等方法,进一步探讨DDPH对缺氧性肺动脉平滑肌细胞(PASMCS)增殖的抑制机制。结果:缺氧促进肺动脉内皮细胞(PAECs)的PDGF·BB和bFGF两种生长因子的表达(积分光密度OD值)增高。缺氧内皮细胞条件培养液(HECCM)能促进PASMCS的PDGF·BB的OD值增高,bFGF的OD值无明显改变。加药组(HEC-CM+DDPH)的PDGF·BB和bFGF的OD值均显著降低,尤以PDGF·BB的OD值减少最多.提示:DDPH能抑制HECCM引起PASMCS的PDGF·BB和bFGF表达增多和细胞增殖。结果与大鼠实验观察相符。 相似文献
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黑线姬鼠肥满度的研究 总被引:10,自引:1,他引:9
黑线姬鼠肥满度的研究STUDYONTHERELATIVEFATNESSOFTHESTRIPEDFIELDMOUSE(APODEMUSAGRARIVS)KeywordsStripedfieldmouse(Apodemus:agrarius);Relat... 相似文献
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低氧对肺动脉内皮细胞PDGF—B链释放及平滑肌细胞生长的影响 总被引:3,自引:0,他引:3
应用蛋白dotblot技术检测了低氧内皮细胞条件培养液(HECCM)和常氧内皮细胞条件培养液(NECCM)内PDGF相对含量,并利用[3H]-TdR掺入法和流式细胞术观察了HECCM和NECCM及加入特异PDGF抗体对肺动脉平滑肌细胞(PASMC)生长的影响。结果表明,HECCM中的PDGF含量明显高于NECCM;HECCM能明显增强PASMC内DNA合成,促进PASMC从Go/G1期进入S期;当预先加入PDGF-B链抗体时,则会明显地抑制HECCM对PASMC的DNA合成,阻止PASMC从Go/G1期进入S期。结果提示,低氧时PASMC增殖与肺动脉内皮细胞分泌释放PDGF增加有关 相似文献
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FasL—Fas/APO—1(CD95)系统 总被引:18,自引:0,他引:18
Fas配体(FasL)与Fas受体(Fas,即APO-1,又称CD95)分别属于肿瘤坏死因子(TNF)及TNF受体(TNFR)家族,以膜分子或可溶性分子形式存在于哺乳类机体内。FasL或Fas单克隆抗体(FasmAb)与Fas结合可引起Fas了性反应细胞的功能增强,继而出现程序性细胞死亡(PCD)。FasL与Fas相互作用及其所介导的信息途径是目前PCD研究的重要内容之一。 相似文献
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磷脂酶A2介导肿瘤坏死因子诱发的中性粒细胞趋化和粘附增强 总被引:3,自引:0,他引:3
肿瘤坏死因子(TNF)对外周中性粒细胞(PMN)具有重要调节作用。本文采用生化及放射免疫技术,观察体外重组TNF对PMN趋化、粘附及血栓素B2(TXB2)和前列环素(6-keto-PGF1a)释放的改变。TNF(100mg/ml)处理60min后,PMM对白细胞趋化因子(FMLP)趋化和玻璃珠粘附性均显著增加,同时伴有TXB2释放增多,6-Keto-PGF1a不变。这提示TNF体外促PMM趋化和粘 相似文献
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血管平滑肌细胞增殖与Cdk抑制蛋白p27的表达 总被引:4,自引:1,他引:4
p27蛋白是细胞周期素依赖性激酶(Cdk)抑制蛋白家族中的一种,主要对外部促进或抑制细胞增殖的信号起反应。本研究应用流式细胞仪(FCM)双标记的方法观察血管紧张素Ⅱ(AngⅡ)、血管加压素(AVP)和血小板源生长因子(PDGF)对血管平滑肌细胞(VSMCs)细胞周期百分比和p27蛋白表达量的影响。静止状态培养的VSMCs加入AngⅡ,AVP,PDGFBB后,在不同时间收集细胞,用碘化丙啶(PI)标记细胞DNA,以确定细胞所处的周期。用p27蛋白的单抗和标记了FITC的二抗标记细胞,通过流式细胞仪测定被激发出的荧光量来确定细胞p27蛋白表达的相对量。结果显示,AngⅡ刺激VSMCs增生,其蛋白含量增加了436%(P<001),但不抑制p27蛋白的表达;AVP可轻度抑制p27的表达,有轻度促进VSMCs增殖和增生的作用(P<005);PDGF明显抑制p27的表达,引起细胞增殖。本研究结果提示,p27蛋白抑制VSMCs通过G1期进入S期,是抑制VSMCs增殖的重要调节因子。 相似文献
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本实验应用免疫组织化学方法,检测巨噬细胞相关抗原、巨噬细胞集落刺激因子(M┐CSF)、白细胞介素┐1(IL┐1)和肿瘤坏死因子┐α(TNF┐α)在骨巨细胞瘤(GCT)中的表达,结果表明,在GCT中,M┐CSF主要由纤维母细胞样基质细胞(FC)分泌;巨噬细胞样基质细胞(HC)是单核┐巨噬细胞系早期的未成熟细胞,主要分泌IL┐1和TNF┐α,少数多核巨细胞(MGC)也可产生TNF┐α。本文提示,GCT中的三种主要细胞能分泌M┐CSF、IL┐1和TNF┐α细胞因子,通过自分泌或旁分泌作用相互影响,共同促进GCT的发生、发展及其侵袭性的生物学行为 相似文献
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Carole Le Contel Anne P. Beigneux Jian Huang Monique A. Parant 《FEMS immunology and medical microbiology》1995,11(4):297-305
Abstract The effect of cyclosporin A (CsA) on tumor necrosis factor (TNF) or interleukin-6 (IL-6) production was evaluated in vivo in primed or unprimed mice challenged with lipopolysaccharide (LPS). Both pretreatment with BCG infection or with muramyl dipeptide (MDP) prior to LPS challenge resulted in an increase in the cytokine bioactivity level in the blood. CsA administration inhibited the TNF production. In unprimed mice, either normal or sensitized to LPS lethality by galactosamine treatment, a marked decrease in the cytokine level was observed after injection of CsA. After adrenalectomy, the yield of both TNF and IL-6 following LPS injection was markedly elevated but decreased by CsA administration. Ex vivo experiments have shown that the inhibitory effect of CsA could be demonstrated at the level of macrophages from mice previously given the drug. If mice had received MDP, in vitro responses of cells to LPS were enhanced but again CsA decreased the mRNA expression and protein secretion. 相似文献
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A L Rakhmilevich M S Rakhimova T M Andronova N V Bovin 《Antibiotiki i khimioterapii͡a》1989,34(8):586-589
The effect of muramyldipeptide (MDP), glucosaminylmuramyldipeptide (GMDP) and their six synthetic derivatives on production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-2 (IL-2) by murine spleen cells in vitro was studied. MDP induced insignificant TNF production and did not stimulate production of IL-1 by the murine splenocytes within a 24-hour cultivation period whereas in combination with lipopolysaccharide (LPS) it induced significant production of both the cytokins. GMDP induced marked production of TNF (54 per cent cytotoxic index) and IL-1 (stimulation index 8). Addition of LPS in an amount of 10 ng/ml increased production of TNF by the murine splenocytes under the effect of GMDP but had no effect on production of IL-1. Neither MDP nor GMDP even in combination with LPS induced production of IL-2 by splenocytes of mice DVA/2 and C57B1/6 at activation for 24 hours. All the synthetic derivatives of MDP and GMDP except the MDP polymer activated TNF production by the murine spleen cells. GMDP lysine had the highest effect: 67 per cent cytotoxic index. In combination with LPS its cytotoxic index amounted to 87 per cent. The TNF activity was always higher when LPS in an amount of 10 ng/ml was added to the glycopeptides. 相似文献
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B B Fuks A L Rakhmilevich A A Pimenov A G Dubrovskaia 《Biulleten' eksperimental'no? biologii i meditsiny》1987,104(10):497-499
The effect of bacterial lipopolysaccharide (LPS), muramyl dipeptide (MDP) and their combination on the production of tumour necrosis factor by spleen cells in vitro and on tumour regression in vivo has been studied. TNF activity was detected in spleen cell supernatants and serum of mice treated with drugs, using L929 cells as targets. The combination of LPS and MDP was more effective in TNF production than each of the drugs used alone in vitro and in vivo. The injection of LPS and MDP to A/Sn mice with subcutaneous nodes of sarcoma SA-I resulted in total tumour necrosis. The treatment of mice with these drugs in water solutions was more effective, however, more toxic than the administration of LPS-treated splenocytes in MDP solution. 相似文献
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The synthetic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), is reported to increase slow-wave sleep and body temperature in cats, rabbits, and squirrel monkeys. The present study examined the ability of MDP to induce sleep and fever in rats. MDP was administered IP at 50, 250 and 500 micrograms/kg. Sleep and body temperature were monitored for 12 hr. MDP failed to affect the duration of wakefulness, S1, S2, or total (S1 + S2) slow-wave sleep. There was also no change in the latency to the first episode of S2 sleep. In contrast, rapid-eye-movement (REM) sleep was significantly suppressed for the first 6 hr after 250 and 500 microgram/kg doses of MDP. There was, however, a rebound increase in REM sleep after the initial period of suppression which resulted in no overall change in the amount of REM sleep. Body temperature was unaffected by MDP. Thus, we conclude that MDP has neither sleep-promoting nor pyrogenic actions in the rat when administered systemically at doses reported to be effective in several other species. 相似文献
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A L Rakhmilevich T L Migdal M S Rakhimova M A Shne?derova V Ia Chirva A E Zemliakov 《Antibiotiki i khimioterapii͡a》1989,34(11):836-839
Production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by macrophages of the spleen and peritoneal exudate of mice as well as cytotoxic factors (CFs) by murine splenocytes after in vitro activation was estimated. All the derivatives of muramyldipeptide (MDP) and glucosaminylmuramyldipeptide (GMDP) were able to induce production of TNF and CFs. In the presence of lipopolysaccharide (LPS), the effect was always higher. The response of the spleen macrophages to the effect of the preparations was higher than that of the peritoneal ones and ++non-fractionated splenocytes. GMDP and GMDP4 especially in the presence of LPS had the highest effect on induction of IL-1 by the murine peritoneal macrophages. On the contrary, MDP induced higher IL-1 synthesis by the spleen macrophages. The most active substances with respect to production of TNF, CFs and IL-1, i.e. MDP3 and GMDP4, might be recommended for immunotherapy of syngeneic tumors in animals. 相似文献
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目的:观察地西泮和戊巴比妥纳对不同种属小鼠自主活动和睡眠效应的影响,为筛选影响中枢神经系统功能的药物提供可参考的选择动物的依据。方法:分别取昆明种和ICR小鼠各40只,设对照组和地西泮给药组,每组20只,给药组ig地西泮4mg/kg,对照组给生理盐水,连续3天,末次给药后45分钟测定小鼠自主活动。另取两种小鼠各20只,分别ip戊巴比妥钠50mg/kg,观察两种小鼠的睡眠情况,记录潜伏期和睡眠时间。结果:ICR小鼠ig地西泮后,表现明显的镇静作用,自主活动的次数和对照组比较明显减少,P〈0.01;而昆明种小鼠给相同剂量的地西泮,小鼠自主活动的次数减少不明显,P〉0.05。昆明种和ICR小鼠同样ip阈上剂量的戊巴比妥钠,两者在睡眠潜伏期上无明显差异,但在睡眠时间上,则ICR小鼠的睡眠时间明显长于昆明种小鼠,P〈0.01。结论:ICR小鼠对中枢抑制药的反应性更好,适合于这类药物的筛选,尤其对作用相对较弱的中药制剂,可能提高筛选的阳性率。 相似文献
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Louis Chedid 《Microbiology and immunology》1983,27(9):723-732
Synthetic N-acetylmuramyl-L -alanyl-d-isoglutamine, also called MDP for muramyl dipeptide, is a copy of a fragment of bacterial peptidoglycan. Soon after the recognition of MDP as being the minimal subunit responsible for the activity of Freund's complete adjuvant, a great number of derivatives were synthesized. Because of their very low molecular weight it was hoped that they could retain selectively certain of the numerous effects produced by complex bacterial agents. Evidence was gathered showing MDP's direct effect on lymphocytes and on macrophages. The ensuing studies reviewed that MDP and several of its derivatives have marked immunopharmacological and neuropharmacological activities. Thus, besides being adjuvants, they are capable of producing hyperthermia by acting directly on thermoregulation centers or by inducing in vivo and in vitro endogenous pyrogens (EP). More recently, Krueger et al have shown that slow-wave sleep (SWS) factor was a muramyl peptide of a molecular weight close to 1,000 daltons. They have also shown that MDP and several of its synthetic analogs had a somnogenic activity. It has previously been hypothesized that several of the immunological activities of the muramyl peptides could be due to biological mimicry with endogenous products. Recent observations argue in favor of the presence of an MDP bacterial structure in mammalian mediators which increase slow-wave sleep and/or produce fever. The implications of these findings will be discussed. 相似文献
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Tumor necrosis factor (TNF), which was originally identified as a tumoricidal factor, is now regarded as one of the main regulators of inflammation and various immune systems. Thus it has been considered to be mobilized in case of emergency. However, we assume that TNF and the cytokine network driven by the monokine also function under normal condition for homeostasis of the animal body which is exposed to various kinds of physiological stress. To test this possibility, we exposed C3H/He mice for up to 3 days to five types of acute stress: food deprivation, drinking water deprivation, sleep deprivation, swimming, and physical restraint. After release from the stress, the level of priming for systemic production of TNF was examined using OK-432 (a streptococcal preparation) as a trigger. Priming of TNF production was not observed immediately after 2-day exposure to most of the stressors. Sleep deprivation alone tended to induce a primed state especially when the stress period was lengthened to 3 days. On the other hand, by keeping mice in a normal condition for a 2-day restorative interval after 2-day exposure to the stressors, systemic production of TNF was consistently primed for all the stress examined. The time course of the priming effect was examined in detail for water-deprivation stress. The effect was detected as early as 3 hours after release from stress, was sustained for 2 days, and returned to the basal level by 4 days after the release. Based on these results, we discussed the role of the TNF-driven cytokine circuit in adaptation to stress. 相似文献
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Shuqin Zhan Pulin Che Xue‐ke Zhao Ning Li Yan Ding Jianghong Liu Spring Li Karyn Ding Lynn Han Zhaoyang Huang Liyong Wu Yuping Wang Meng Hu Xiaosi Han Qiang Ding 《Journal of cellular and molecular medicine》2019,23(10):6822-6834
Hypocretin 1 and hypocretin 2 (orexin A and B) regulate sleep, wakefulness and emotion. Tumour necrosis factor alpha (TNF‐α) is an important neuroinflammation mediator. Here, we examined the effects of TNF‐α treatment on hypocretin expression in vivo and behaviour in mice. TNF‐α decreased hypocretin 1 and hypocretin 2 expression in a dose‐dependent manner in cultured hypothalamic neurons. TNF‐α decreased mRNA stability of prepro‐hypocretin, the single precursor of hypocretin 1 and hypocretin 2. Mice challenged with TNF‐α demonstrated decreased expression of prepro‐hypocretin, hypocretin 1 and hypocretin 2 in hypothalamus. In response to TNF‐α, prepro‐hypocretin mRNA decay was increased in hypothalamus. TNF‐α neutralizing antibody restored the expression of prepro‐hypocretin, hypocretin 1 and hypocretin 2 in vivo in TNF‐α challenged mice, supporting hypocretin system can be impaired by increased TNF‐α through decreasing hypocretin expression. Repeated TNF‐α challenge induced muscle activity during rapid eye movement sleep and sleep fragmentation, but decreased learning, cognition and memory in mice. TNF‐α neutralizing antibody blocked the effects of TNF‐α; in contrast, hypocretin receptor antagonist enhanced the effects of TNF‐α. The data support that TNF‐α is involved in the regulation of hypocretin expression, sleep and cognition. The findings shed some lights on the role of neuroinflammation in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. 相似文献