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n-3脂肪酸调节肥胖巨大儿大鼠的T细胞钙信号传导。

n-3 fatty acids modulate T-cell calcium signaling in obese macrosomic rats.

作者信息

Guermouche Baya, Yessoufou Akadiri, Soulimane Nassima, Merzouk Hafida, Moutairou Kabirou, Hichami Aziz, Khan Naim Akhtar

机构信息

Départment de Biologie, Faculté des Sciences, Université de Tlemcen, Algeria.

出版信息

Obes Res. 2004 Nov;12(11):1744-53. doi: 10.1038/oby.2004.216.

DOI:10.1038/oby.2004.216
PMID:15601968
Abstract

OBJECTIVE

We investigated the effects of a diet containing EPAX-7010, rich in PUFAs such as eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)], i.e., a PUFA/EPAX regimen, on T-cell activation in diabetic pregnant rats and their obese pups.

RESEARCH METHODS AND PROCEDURES

Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on Day 5 of gestation. T-cell blastogenesis was assayed by using (3)H-thymidine, whereas intracellular free calcium concentrations ([Ca(2+)]i) were measured by using Fura-2 in diabetic pregnant rats and their obese offspring.

RESULTS

Concavalin-A-stimulated T-cell proliferation was decreased in both pregnant diabetic rats and their obese pups as compared with control animals. Feeding the PUFA/EPAX diet restored T-cell proliferation in both groups of animals. We also employed ionomycin, which at 50 nM opens calcium channels, and thapsigargin (TG), which recruits [Ca(2+)]i from endoplasmic reticulum pool. We observed that ionomycin-induced increases in [Ca(2+)]i in T-cells of diabetic mothers and obese offspring were greater than in those of control rats. Furthermore, feeding PUFA/EPAX diet diminished significantly the ionomycin-evoked rise in [Ca(2+)]i in diabetic and obese animals. TG-induced increases in [Ca(2+)]i in T-cells of diabetic pregnant rats and their obese offspring were greater than in those of control rats. The feeding of the experimental diet significantly curtailed the TG-evoked increases in [Ca(2+)]i in both diabetic and obese rats.

DISCUSSION

Together, these observations provide evidence that T-cell activation and T-cell calcium signaling are altered during gestational diabetes and macrosomia. Hence, dietary fish oils, particularly eicosapentaenoic acid and docosahexaenoic acid, may restore these T-cell abnormalities.

摘要

目的

我们研究了一种富含二十碳五烯酸[20:5(n - 3)]和二十二碳六烯酸[22:6(n - 3)]等多不饱和脂肪酸的饮食,即多不饱和脂肪酸/ EPAX方案(PUFA/EPAX方案),对糖尿病妊娠大鼠及其肥胖幼崽T细胞活化的影响。

研究方法和步骤

妊娠第5天腹腔注射链脲佐菌素诱导妊娠大鼠轻度高血糖。用³H - 胸腺嘧啶测定T细胞增殖,而用Fura - 2测量糖尿病妊娠大鼠及其肥胖后代的细胞内游离钙浓度([Ca²⁺]i)。

结果

与对照动物相比,妊娠糖尿病大鼠及其肥胖幼崽中刀豆蛋白A刺激的T细胞增殖均降低。给予PUFA/EPAX饮食可恢复两组动物的T细胞增殖。我们还使用了离子霉素(50 nM时可打开钙通道)和毒胡萝卜素(TG),后者可从内质网池中募集[Ca²⁺]i。我们观察到,离子霉素诱导的糖尿病母亲和肥胖后代T细胞中[Ca²⁺]i的增加大于对照大鼠。此外,给予PUFA/EPAX饮食可显著降低离子霉素诱发的糖尿病和肥胖动物中[Ca²⁺]i的升高。TG诱导的糖尿病妊娠大鼠及其肥胖后代T细胞中[Ca²⁺]i的增加大于对照大鼠。给予实验饮食可显著减少糖尿病和肥胖大鼠中TG诱发的[Ca²⁺]i的增加。

讨论

总之,这些观察结果提供了证据,表明妊娠期糖尿病和巨大儿期间T细胞活化和T细胞钙信号传导发生改变。因此,膳食鱼油,特别是二十碳五烯酸和二十二碳六烯酸,可能恢复这些T细胞异常。

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