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1.
Lingyun Hao Ling Dong Qiuxing Yu Wen Shen Xuewen Wei 《Fundamental & clinical pharmacology》2020,34(6):662-670
Previous studies have demonstrated that excessive free radicals play an essential role in the initiation and progression of epilepsy and that a novel exogenous free radical scavenger edaravone (Ed) exerts some neuroprotective effects on seizure-induced neuronal damage. The purpose of this study was to elucidate the possible molecular mechanisms of Ed associated with procaspase-3 denitrosylation and activation through the FasL-Trx2 pathway in seizures rats. In this study, we investigated the effects of Ed on the regulation of the combination of Fas ligand/Fas receptor and the major components of the death-inducing signaling complex (DISC) in the hippocampus of kainic acid (KA)-treated Sprague Dawley (SD) rats. Treatment with Ed can attenuate the increased expression of FasL induced by KA and prevent procaspase-3 denitrosylation and activation via suppression of the FasL-Trx2 signaling pathway, which alleviates the neuronal damage in seizures. These results provide experimental evidence that Ed functions by preventing the denitrosylation and activation of procaspase-3 and that Ed acts as a therapeutic option for epilepsy. 相似文献
2.
目的观察依达拉奉对脓毒性休克大鼠存活率的影响及肾损伤的保护作用。方法 Wistar大鼠96只(200±20)g,第一批46只分4组,即脓毒性休克模型组(L组,n=16),脓毒性休克1h后予依达拉奉(6.0、3.0和1.5mg/kg)3个剂量组(EH、EM、EL组,n=10)治疗,观察其24h动物存活情况;另一批50只分手术对照组(仅予生理盐水治疗)、L组、EH组、EM组、EL组5组,每组各10只。大鼠脓毒性休克1h后予如前处理,于休克6h后取肾组织测取超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、乳酸脱氢酶(LDH)活性和乳酸(LD)、丙二醛(MDA)含量,并观察形态学改变。结果与脓毒性休克组比较,依达拉奉治疗后死亡率明显低于模型组(P<0.05),且其作用呈量效关系,3个剂量组死亡率分别为10%、10%、30%。同时,依达拉奉可显著升高肾组织中的SOD并降低LDH、MDA活性、降低LD水平。组织学观察可见未治疗组肾小球肿胀、间质水肿、出血、炎性细胞浸润等变化,依达拉奉治疗后上述变化明显改善。结论依达拉奉能明显降低脓毒性休克大鼠的死亡率,减少肾组织损伤,其机制与提高脓毒性休克机体的抗氧化能力有关。 相似文献
3.
目的 使用依达拉奉联合尿激酶静脉溶栓治疗急性脑梗死患者,对其效果进行观察。方法 对滑县人民医院2016年2月—2017年5月收治的87例急性脑梗死患者分组研究,随机分成研究组(n=44)与参照组(n=43),参照组行尿激酶静脉溶栓治疗,研究组在此基础上联合依达拉奉治疗,比较并分析两组治疗结果。结果 2组治疗前炎性因子水平相比,差异无统计学意义(P>0.05),研究组治疗后hs-CRP、TNF-α水平与参照组相比,相对更低(P<0.05);两组治疗前NIHSS、ADL评分相比,组间差异无统计学意义(P>0.05),观察组治疗后NIHSS评分低于参照组(P<0.05),观察组ADL评分低于参照组(P<0.05);研究组总有效率为93.18%,高于参照组的72.09%(P<0.05)。结论 对急性脑梗死患者应用依达拉奉联合尿激酶静脉溶栓治疗效果较好,可缓解患者神经功能缺损程度,减轻炎症反应,提升其日常生活能力,值得推广应用。 相似文献
4.
Neuroprotective effect of edaravone in experimental glaucoma model in rats: a immunofluorescence and biochemical analysis 下载免费PDF全文
AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats.
METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group. Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally 3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other 16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells (RGCs) have been marked with dextran tetramethylrhodamine (DTMR) retrograde at the end of the sixth week and after 48h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the whole-mount retina. Whole-mount retinal tissues homogenized and nitric oxide (NO), malondialdehyde (MDA) and total antioxidant capacity (TAC) values were measured biochemically.
RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group (Bonferroni, P<0.05). The neuroprotective activity of edaravone was found to be more influential by administration at the start of the glaucoma process. Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups (Bonferroni, P<0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group (Bonferroni, P<0.05).
CONCLUSION: Systemic administration of Edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results. 相似文献
5.
目的观察单唾液酸神经节苷脂( GM1)联合依达拉奉对局灶性脑缺血再灌注大鼠缺血半暗带区PDK1、GSK3β蛋白表达的影响,探讨其可能的作用。方法随机将大鼠分为假手术组、模型组、GM1组(剂量20 mg/kg,腹腔注射,1次/d)、依达拉奉组(剂量3 mg/kg,腹腔注射,2次/d)、GM1联合依达拉奉组,采用线栓法制作大鼠大脑中动脉缺血再灌注模型,分别对缺血2 h后再灌注3、7、14 d,采用免疫组化Envision两步法检测大鼠模型缺血半暗带PDK1、GSK3β蛋白表达的阳性细胞平均吸收光密度和阳性面积单位。结果
在缺血半暗带,再灌注3、7、14 d各时间点,GM1联合依达拉奉组PDK1蛋白表达平均吸收光密度和阳性面积单位分别显著高于 GM1组、依达拉奉组( P<0.05)、模型组( P <0.01),GSK3β蛋白表达平均吸收光密度和阳性面积单位分别显著低于 GM1组、依达拉奉组( P<0.01)、模型组( P <0.01)。结论 GM1联合依达拉奉能增强缺血半暗带PDK1蛋白表达,抑制GSK3β蛋白表达。 相似文献
在缺血半暗带,再灌注3、7、14 d各时间点,GM1联合依达拉奉组PDK1蛋白表达平均吸收光密度和阳性面积单位分别显著高于 GM1组、依达拉奉组( P<0.05)、模型组( P <0.01),GSK3β蛋白表达平均吸收光密度和阳性面积单位分别显著低于 GM1组、依达拉奉组( P<0.01)、模型组( P <0.01)。结论 GM1联合依达拉奉能增强缺血半暗带PDK1蛋白表达,抑制GSK3β蛋白表达。 相似文献
6.
目的:观察氧自由基清除剂依达拉奉预处理对老年患者膝关节置换术后认知功能的影响。方法选择2014年5-9月在我院择期全麻下行全膝关节置换术的老年患者90例,年龄60~79岁,ASAⅠ~Ⅱ级,术前简易精神状态检查表(mini-mental state examination,MMSE)评分≥23分,随机分为2组,依达拉奉组(E组)和对照组(C组),每组45例,分别于麻醉诱导前30 min给予依达拉奉0.5 mg/kg(E组)和等量的氯化钠注射液(C组)。于术前1 d(T0)、术后第1天(T1)、术后第5天(T2)采用国际术后认知功能障碍研究协作组(international study of postoperative cognitive dysfunction,ISPOCD)推荐的量表对患者的认知功能进行评估。结果 T0时两组神经心理学评估量表评分无统计学差异(P>0.05)。两组术后认知功能障碍(postoperative cognitive dysfunction,POCD)发生率在T1时E组11.11%、C组33.33%;在T2时E组6.67%、C组22.22%, T1、T2时,E组POCD的发生率均低于C组(P=0.01,P=0.04)。结论依达拉奉预处理可以降低老年患者膝关节置换术POCD的发生率,改善老年患者的术后认知功能。 相似文献
7.
目的:评估依达拉奉在治疗急性脑梗死和脑出血疾病中的疗效。方法急性脑梗死患者251例,脑出血患者204例及体检健康者485例为研究对象,455例脑梗死及脑出血患者分为普通用药组和依达拉奉联合普通用药组,比较2组患者在治疗不同时期血清超氧化物歧化酶(SOD)和同型半胱氨酸(Hcy)水平变化,以及患者出院时的恢复情况及转归。结果依达拉奉联合普通用药组与普通用药组治疗7 d 后血清 SOD 水平明显高于普通用药组,而 Hcy 水平低于普通用药组,差异均有统计学意义(P<0.05);依达拉奉联合普通用药组恢复良好的患者比率明显高于普通用药组,差异有统计学意义(χ2=7.962,P=0.005)。结论依达拉奉与普通溶栓或止血药联合应用可以有效提高治疗效果,延缓病情发展,降低致残率、致死率,提高患者的生活质量。 相似文献
8.
Kai Hua Xiao Sheng Ting-ting Li Lin-na Wang Yi-hua Zhang Zhang-jian Huang Hui Ji 《Acta pharmacologica Sinica》2015,36(8):917-927
Aim:
Compound 10b is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide (NBP). The aim of this study was to examine the effects of compound 10b on brain damage in rats after focal cerebral ischemia.Methods:
SD rats were subjected to 2-h-middle cerebral artery occlusion (MCAO). At the onset of reperfusion, the rats were orally treated with NBP (60 mg/kg), edaravone (3 mg/kg), NBP (60 mg/kg)+edaravone (3 mg/kg), or compound 10b (70, 140 mg/kg). The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting.Results:
Administration of compound 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α.Conclusion:
Oral administration of compound 10b effectively attenuates rat cerebral ischemia injury. 相似文献9.
目的研究依达拉奉对卵巢癌耐药细胞株A2780CP增殖、凋亡及其对顺铂敏感性的影响。方法选取顺铂和依达拉奉的血药峰值浓度作为联合用药的基础,将实验分为顺铂处理A2780细胞组、顺铂处理A2780CP细胞组、依达拉奉处理A2780CP细胞组、顺铂及依达拉奉联合处理A2780CP细胞组,对照组。培养一定时间后用MTT法检测细胞相对活性,流式细胞仪分析细胞的凋亡状况。结果顺铂及依达拉奉联合处理的A2780cP细胞生长明显慢于单独2780CP细胞,顺铂及依达拉奉联合处理的A2780CP细胞对顺铂的敏感性增加(P=0.016〈0.05);AnnexinV—FITC/P1分析显示,药物作用24小时后,顺铂及依达拉奉联合处理A2780CP细胞能提高细胞凋亡率(P=0.037〈0.05)。结论依达拉奉能显著提高A2780CP细胞对顺铂的敏感性,对顺铂耐药性有一定逆转作用。 相似文献
10.
Manoj Kumar Jaiswal 《Medicinal research reviews》2019,39(2):733-748
Over the past decades, a multitude of experimental drugs have been shown to delay disease progression in preclinical animal models of amyotrophic lateral sclerosis (ALS) but failed to show efficacy in human clinical trials or are still waiting for approval under Phase I–III trials. Riluzole, a glutamatergic neurotransmission inhibitor, is the only drug approved by the USA Food and Drug Administration for ALS treatment with modest benefits on survival. Recently, an antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to be effective in halting ALS progression during early stages. The newly approved drug edaravone is a force multiplier for ALS treatment. This short report provides an overview of the two drugs that have been approved for ALS treatment and highlights an update on the timeline of drug development, how clinical trials were done, the outcome of these trials, primary endpoint, mechanism of actions, dosing information, administration, side effects, and storage procedures. Moreover, we also discussed the pressing issues and challenges of ALS clinical trials and drug developments as well as future outlook. 相似文献