Effect of age receptor blocker and/or anti-inflammatory coadministration in relation to glycation, oxidative stress and cytokine production in STZ diabetic rats
Effect of age receptor blocker and/or anti-inflammatory coadministration in relation to glycation, oxidative stress and cytokine production in STZ diabetic rats
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DOI：
10.1006/phrs.2002.0979
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发表时间：
2002-05-01
影响因子：
9.3
通讯作者：
Hashem, RM
中科院分区：
文献类型：
--
作者：
El-Seweidy, MM;El-Swefy, SE;Hashem, RM
晚期糖基化终末产物（AGES）与血管病变的关系至今仍存在争议。然而，前者与受体的相互作用触发细胞因子的合成，特别是白细胞介素1-β（IL-1 β）和肿瘤坏死因子-α（TNF α）。随后释放的一氧化氮（NO）可能反过来诱导β细胞胰岛的某些损伤。一些论点表明，AGES和活性氧中间体（ROI）可以改变血管壁的功能。因此，本研究旨在研究氨基胍、AG（AGE形成抑制剂）与omega-3-脂肪酸、omega-3 FA（抗炎免疫抑制药）联合治疗STZ糖尿病大鼠的有效性。在48只雌性白化病Wistar大鼠中，通过单次腹腔内（i. p.）注射链脲佐菌素（STZ，50 mg kg（-1））。糖尿病动物每天口服AG（50 mg kg（-1））和/或omega 3FAs（12 mg kg（-1））治疗4周。年龄匹配的糖尿病大鼠组（n=10）和健康动物组（n=10）作为阳性和阴性对照。实验结束时检测血糖、果糖胺、总胆固醇（TC）、高密度脂蛋白胆固醇（HDLC）、低密度脂蛋白胆固醇（LDLC）、低密度脂蛋白对铜催化氧化的敏感性、过氧化氢酶活性、NO、IL-1 β、TNF α。还测定了胰腺切片的组织学评估。糖尿病显著增加血浆葡萄糖、果糖胺和血脂异常（TC、LDL C升高和HDL C降低）。氧化标记物如LDL的氧化敏感性、过氧化氢酶活性和NO水平大大增强。最后，增加细胞因子（IL-1 β和TNF α）的合成和释放。用AG和omega 3FAs治疗糖尿病大鼠显著降低上述参数。联合形式治疗对氧化细胞标志物，特别是NO水平有更好的效果。最后，与糖尿病和AG治疗组相比，ω 3FA与AG联合给药几乎恢复了胰岛的萎缩和外周淋巴细胞浸润。总之，糖基化、氧化应激和细胞因子的产生与STZ糖尿病大鼠微血管病变的倾向增加有直接相关性。与AGE受体阻断剂一起施用ω 3FA可能代表针对减轻与糖尿病相关的并发症的治疗的研究的可能途径。(C)2002爱思唯尔科技有限公司。保留所有权利。
Until now the relation between advanced glycation end products (AGES) and vascular lesion is still controversial. However, the interaction of the former with a receptor triggers the synthesis of cytokines particularly interleukin 1-beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). Subsequent release of nitric oxide (NO) may in turn induce certain damage to beta cell islets. Several arguments indicated that AGES and reactive oxygen intermediates (ROIs) could alter the function of the vessel wall. Therefore, this study was undertaken to investigate the effectiveness of aminoguanidine, AG (inhibitor of AGE formation) joined with omega-3-fatty acids, omega3FAs (anti-inflammatory immunosuppressive drug) in STZ diabetic rats. Diabetes was induced in 48 female albino Wistar rats by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 50 mg kg(-1)). Diabetic animals were treated with AG (50 mg kg(-1)) and/or omega3FAs (12 mg kg(-1)) daily and orally for 4 weeks. Groups of age matched diabetic rats (n=10) and healthy animals (n=10) served as positive and negative controls. At the end of the study, plasma glucose, fructosamine, total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), the susceptibility of LDL to copper-catalysed oxidation, catalase activity, NO, IL-1beta, TNFalpha were measured. Histopathological assessment of pancreatic slices were also determined. Diabetes remarkably increased plasma glucose, fructosamine and dyslipidaemia (increased TC, LDLC and decreased HDLC). Oxidative markers like oxidative susceptibility of LDL, catalase activity and NO levels were greatly enhanced. Finally, it increased the synthesis and release of cytokine (IL-1beta and TNFalpha). Treatment of diabetic rats with AG and omega3FAs markedly reduced the above mentioned parameters. Combined form therapy has a better effect regarding oxidative cell markers, specifically NO level. Finally, omega3FAs coadministration with AG nearly restored the atrophy of islets of Langerhan's and the peripheral lymphocytic infiltration compared to diabetic and AG treated groups. In conclusion, there is a direct correlation between glycation, oxidative stress and cytokine production with increased propensity of microvascular disorder in STZ diabetic rats. omega3FA administration with AGE receptor blocker may represent a possible avenue of research for therapeutics directed for alleviating the complication associated with diabetes. (C) 2002 Elsevier Science Ltd. All rights reserved.