Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.
Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.
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富马酸酯可以阻止人CRP的促炎作用，并在自发性高血压大鼠中改善代谢性障碍。
DOI：
10.1371/journal.pone.0101906
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Pravenec M
中科院分区：
文献类型：
--
作者：
Šilhavý J;Zídek V;Mlejnek P;Landa V;Šimáková M;Strnad H;Oliyarnyk O;Škop V;Kazdová L;Kurtz T;Pravenec M
炎症和氧化应激与代谢紊乱的发病机制有关。富马酸酯，主要是富马酸二甲酯，具有免疫调节、抗炎和抗氧化作用。在目前的研究中，我们测试的假设，富马酸酯（FAE）治疗的动物模型的炎症和代谢综合征，自发性高血压大鼠转基因表达人类C-反应蛋白（SHR-CRP），将改善炎症，氧化应激和代谢紊乱。我们研究了FAE治疗的效果，通过给予Fumaderm，10 mg/kg体重4周，雄性SHR-CRP。未处理的雄性SHR-CRP大鼠用作对照。所有大鼠均喂食高糖饮食。与未处理对照组相比，FAE处理大鼠的内源性CRP水平显著降低，但转基因人CRP水平未降低，炎症（血清IL 6和TNFα水平降低）和氧化应激（肝脏、心脏、肾脏和血浆中脂质过氧化产物水平降低）改善。FAE治疗还与较低的内脏脂肪重量和肝脏和肌肉中的异位脂肪积聚较少、脂解水平较高以及葡萄糖掺入脂肪组织脂质较多相关。用Affyellow阵列分析肝脏中的基因表达谱显示，FAE治疗与涉及炎症和氧化应激调节的途径中的基因差异表达相关。这些发现表明FAE在由人CRP诱导的炎症和代谢紊乱模型中具有潜在的重要抗炎、抗氧化和代谢作用。
Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE) treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP), will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα) and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma). FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.
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影响因子：
5.8
作者：
Chai, Joshua T.;Digby, Janet E.;Choudhury, Robin P.
通讯作者：
Choudhury, Robin P.
影响因子：
37.8
作者：
Koike T;Kitajima S;Yu Y;Nishijima K;Zhang J;Ozaki Y;Morimoto M;Watanabe T;Bhakdi S;Asada Y;Chen YE;Fan J
通讯作者：
Fan J
影响因子：
4.7
作者：
Lin SX;Lisi L;Dello Russo C;Polak PE;Sharp A;Weinberg G;Kalinin S;Feinstein DL
通讯作者：
Feinstein DL
DOI：
10.1161/hypertensionaha.110.164350
发表时间：
2011-04
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Pravenec M;Kajiya T;Zídek V;Landa V;Mlejnek P;Simáková M;Silhavý J;Malínská H;Oliyarnyk O;Kazdová L;Fan J;Wang J;Kurtz TW
通讯作者：
Kurtz TW
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J