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两种源自大蒜的二烯丙基硫化物可抑制糖尿病小鼠的耐甲氧西林金黄色葡萄球菌感染。

Two diallyl sulphides derived from garlic inhibit meticillin-resistant Staphylococcus aureus infection in diabetic mice.

作者信息

Tsao Shih-Ming, Liu Wen-Hu, Yin Mei-Chin

机构信息

Department of Infection, Chung Shan Medical University Hospital, Taichung City, Taiwan, Republic of China.

Department of Nutritional Science, Chung Shan Medical University, Taichung City, Taiwan, Republic of China.

出版信息

J Med Microbiol. 2007 Jun;56(Pt 6):803-808. doi: 10.1099/jmm.0.46998-0.

Abstract

The inhibitory effect of diallyl sulphide (DAS) and diallyl disulphide (DADS) against meticillin-resistant Staphylococcus aureus (MRSA) infection in diabetic mice was studied. The influence of these agents on the plasma levels of fibronectin, C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-alpha), and on the activity of plasminogen activator inhibitor-1 (PAI-1), antithrombin III (AT-III) and protein C, in MRSA-infected diabetic mice was examined. To induce diabetes, mice were treated intraperitoneally with streptozotocin for 5 consecutive days. Ten clinical MRSA isolates obtained from infected patients were used in this study. Diabetic mice were infected by injecting 200 microl MRSA/PBS suspension containing 10(7) c.f.u. via the tail vein. At day 4 post-infection, 200 microl DAS or DADS was administrated twice orally with an interval of 12 h. Eight hours after each administration, the blood and organs of mice were collected. Results showed that DAS and DADS significantly decreased MRSA viability in the kidney (P<0.05), with administration of each agent twice showing a greater inhibitory effect than when given once (P<0.05). MRSA infection in diabetic mice significantly elevated the plasma levels of IL-6 and TNF-alpha (P<0.05). DAS or DADS given once did not affect the plasma levels of IL-6 and TNF-alpha (P>0.05); however, DAS or DADS given twice significantly decreased the plasma levels of both IL-6 and TNF-alpha (P<0.05). DAS and DADS treatments also significantly reduced the plasma levels of CRP, fibronectin and fibrinogen (P<0.05). DAS or DADS treatment did not affect PAI-1 activity (P>0.05), but DAS or DADS given twice significantly increased AT-III activity (P<0.05). DADS given twice elevated protein C activity (P<0.05). MRSA infection significantly increased malondialdehyde levels in the kidney and spleen (P<0.05), and these levels were significantly decreased by treatment with DAS or DADS (P<0.05). These data suggest that DAS and DADS could provide multiple protective functions against MRSA infection in diabetic mice.

摘要

研究了二烯丙基硫醚(DAS)和二烯丙基二硫醚(DADS)对糖尿病小鼠耐甲氧西林金黄色葡萄球菌(MRSA)感染的抑制作用。检测了这些药物对MRSA感染的糖尿病小鼠血浆中纤连蛋白、C反应蛋白(CRP)、纤维蛋白原、白细胞介素(IL)-6和肿瘤坏死因子-α(TNF-α)水平,以及对纤溶酶原激活物抑制剂-1(PAI-1)、抗凝血酶III(AT-III)和蛋白C活性的影响。为诱导糖尿病,小鼠连续5天腹腔注射链脲佐菌素。本研究使用了从感染患者中分离得到的10株临床MRSA菌株。通过尾静脉注射200微升含10⁷ 菌落形成单位(c.f.u.)的MRSA/PBS悬液感染糖尿病小鼠。感染后第4天,口服给予200微升DAS或DADS,间隔12小时给药两次。每次给药8小时后,采集小鼠的血液和器官。结果显示,DAS和DADS显著降低了肾脏中MRSA的活力(P<0.05),每种药物给药两次的抑制作用比给药一次更强(P<0.05)。糖尿病小鼠的MRSA感染显著升高了血浆中IL-6和TNF-α的水平(P<0.05)。给药一次的DAS或DADS对血浆中IL-6和TNF-α的水平没有影响(P>0.05);然而,给药两次的DAS或DADS显著降低了血浆中IL-6和TNF-α的水平(P<0.05)。DAS和DADS治疗还显著降低了血浆中CRP、纤连蛋白和纤维蛋白原的水平(P<0.05)。DAS或DADS治疗对PAI-1活性没有影响(P>0.05),但给药两次的DAS或DADS显著增加了AT-III活性(P<0.05)。给药两次的DADS提高了蛋白C活性(P<0.05)。MRSA感染显著增加了肾脏和脾脏中丙二醛的水平(P<0.05),而DAS或DADS治疗可显著降低这些水平(P<0.05)。这些数据表明,DAS和DADS可以为糖尿病小鼠抵抗MRSA感染提供多种保护作用。

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