目的 探讨不同剂量左甲状腺素(L-T4)对缺氧缺血性脑损伤(hypoxia-ischemia brain damage, HIBD)新生大鼠脑组织缺氧诱导因子-1α(hypoxia-inducible factor 1α, HIF-1α)的调节作用。方法 7日龄SD大鼠随机分为假手术组、缺氧缺血组(HI)、溶剂组及L-T4低、高剂量组。低、高剂量L-T4干预组及溶剂对照组分别于HIBD后当日起腹腔注射2 μg/100 g L-T4、3.5 μg/100 g L-T4及等体积溶剂, 每日1次, 共5 d。应用免疫组化法检测鼠脑HIF-1α蛋白, RT-PCR法检测HIF-1αmRNA。结果 缺氧缺血组缺血侧大脑皮质HIF-1α蛋白(72.795±6.121)及HIF-1αmRNA(0.448±0.035)表达较假手术组(依次为38.581±2.846, 0.174±0.015)增高, 差异有统计学意义(P＜0.05);L-T4低、高剂量干预组缺血侧大脑皮质HIF-1α蛋白(依次为117.350±9.374, 142.842±8.948)及HIF-1αmRNA(依次为0.618±0.042, 0.711±0.049)表达较缺氧缺血组增高, 差异有统计学意义(P＜0.05), 且L-T4对HIF-1α的影响具有剂量依赖性, 即随剂量增加, HIF-1α蛋白及HIF-1αmRNA表达增加, 两组间差异具有统计学意义(P<0.05)。结论 在新生大鼠HIBD时, L-T4可上调HIF-1α蛋白及其mRNA表达, 从而对HIBD起保护作用, 且具有剂量依赖性。
Abstract
Objective To observe the expression of hypoxia-inducible factor 1α(HIF-1α) in rat brain after hypoxia-ischemia brain damage (HIBD) and L-thyroxine (L-T4) of different dose treated. Methods Eighty postnatal 7 days old Sprague-Dawley(SD) rats were randomly divided into 5 groups :the sham operation group, hypoxia-ischemia group (HI), menstruum-treated group, L-T4-treated groups of low and high dose.The rats of menstruum-treated, L-T4-treated groups of low and high dose were respectively daily administrated of intraperitoneal injection of menstruum of the equal volume and 2 μg/100 g L-T4, 3.5 μg/100 g, once a day, for 5 days.The expression of HIF-1α were detected by immunohistochemistry.Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect the level of HIF-1α mRNA. Results Compared with the sham operation group, the levels of HIF-1α protein(38.581±2.846) and HIF-1α mRNA(0.174±0.015) were upregulated in HI group(72.795±6.121, 0.448±0.035 respectively), as well as in menstruum-treated group.The levels of HIF-1α protein (117.350±9.374, 142.842±8.948 respectively)and HIF-1α mRNA(0.618±0.042, 0.711±0.049 respectively) in L-T4-treated groups of low and high dose were higher than HI group(P<0.05).The influence of L-T4 on HIF-1α protein and HIF-1α mRNA was dose dependent, namely with the increase of dose, their expression increased (P<0.05). Conclusion L-T4 upregulats HIF-1α mRNA and protein expression in neonatal rats with HIBD.
关键词
缺氧诱导因子1-α /
左甲状腺素 /
缺氧缺血性脑损伤 /
新生大鼠
Key words
hypoxia-inducible factor 1α /
L-thyroxine /
hypoxia-ischemia brain damage /
neonatal rat
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基金
2013年河南省教育厅自然科学研究计划项目(13A320664)
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