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刺毛黧豆提取物抗蛇毒作用相关病理生理过程的蛋白质组学分析

Proteomic analysis of the pathophysiological process involved in the antisnake venom effect of Mucuna pruriens extract.

作者信息

Guerranti Roberto, Ogueli Ifeanyi G, Bertocci Erica, Muzzi Chiara, Aguiyi John C, Cianti Riccardo, Armini Alessandro, Bini Luca, Leoncini Roberto, Marinello Enrico, Pagani Roberto

机构信息

Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Via A. Moro 2, Siena, Italy.

出版信息

Proteomics. 2008 Jan;8(2):402-12. doi: 10.1002/pmic.200700265.

Abstract

Previously, we reported the antisnake venom properties of a Mucuna pruriens seed extract (MPE) and tested its in vivo efficacy against Echis carinatus venom (EV) in short- (1 injection) and long-term (three weekly injections) treatments. The aim of the present study was to investigate plasma proteome changes associated with MPE treatments and identify proteins responsible for survival of envenomated mice (CHALLENGED mice). Six treatment groups were studied. Three control groups: one saline, one short-term and one long-term MPE treatment. One group received EV alone. Two test groups received EV with either a short-term or long-term MPE treatment (CHALLENGED mice). The plasma from each group was analysed by 2-DE/MALDI-TOF MS. The most significant changes with treatment were: albumin, haptoglobin, fibrinogen, serum amyloid A and serum amyloid P. Most of these changes were explained by EV effects on coagulation, inflammation and haemolysis. However, MPE treatments prevented the EV-induced elevation in HPT. Consequently, HPT levels were similar to controls in the plasma of CHALLENGED mice. The plasma of CHALLENGED mice showed substantial proteomic modifications. This suggests the mechanism of MPE protection involves the activation of counterbalancing processes to compensate for the imbalances caused by EV.

摘要

此前,我们报道了刺毛黧豆种子提取物(MPE)的抗蛇毒特性,并在短期(单次注射)和长期(每周注射三次)治疗中测试了其对锯鳞蝰蛇毒(EV)的体内疗效。本研究的目的是调查与MPE治疗相关的血浆蛋白质组变化,并确定对被蛇毒咬伤小鼠(受挑战小鼠)存活起作用的蛋白质。研究了六个治疗组。三个对照组:一组为生理盐水组,一组为短期MPE治疗组,一组为长期MPE治疗组。一组单独接受EV。两个测试组接受EV并分别进行短期或长期MPE治疗(受挑战小鼠)。通过二维电泳/基质辅助激光解吸电离飞行时间质谱对每组血浆进行分析。治疗引起的最显著变化为:白蛋白、触珠蛋白、纤维蛋白原、血清淀粉样蛋白A和血清淀粉样蛋白P。这些变化大多可由EV对凝血、炎症和溶血的影响来解释。然而,MPE治疗可防止EV诱导的肝促凝血酶原激酶升高。因此,受挑战小鼠血浆中的肝促凝血酶原激酶水平与对照组相似。受挑战小鼠的血浆显示出大量蛋白质组学修饰。这表明MPE的保护机制涉及激活平衡过程,以补偿由EV引起的失衡。

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