Different effects of arginine vasopressin on high-mobility group box 1 expression in astrocytes isolated from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats
Different effects of arginine vasopressin on high-mobility group box 1 expression in astrocytes isolated from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats
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DOI：
10.1111/iep.12172
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发表时间：
2016-04-01
影响因子：
3
通讯作者：
Nabika, Toru
中科院分区：
文献类型：
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作者：
Yamagata, Kazuo;Sone, Natumi;Nabika, Toru
易卒中的自发性高血压大鼠（SHRSP/Izm）在缺血刺激后发生严重的高血压和星形胶质细胞水肿。在缺血性应激期间，诱导星形胶质细胞中的高迁移率族蛋白1（Hmgb 1）表达，并且随后由于缺血性损伤而增强脑的恶化，其表现为脑炎症和星形胶质细胞水肿。精氨酸加压素（AVP）可诱导脑损伤并增加星形胶质细胞肿胀。中风后，Hmgb1和过氧化物酶（Prx）在不同的时间释放，并通过Toll样受体（Tlr2）激活大脑中的巨噬细胞。本研究的目的是检查是否AVP和/或缺氧/复氧（H/R）有助于缺血性脑卒中后Hmgb1的调节。因此，比较了从用AVP和/或H/R处理的Wistar京都大鼠（WKY/Izm）、自发性高血压大鼠（SHR/Izm）、SHRSP/Izm和同类大鼠品系SHRpch 1_18分离的星形胶质细胞中Hmgb 1、Prx 2和Tlr 2的表达水平。通过逆转录聚合酶链反应（RT-PCR）和实时定量PCR以及Western blot测定基因和蛋白表达水平。AVP诱导的Hmgb 1、Prx 2和Tlr 2 mRNA表达呈剂量依赖性，SHR/Izm、SHRSP/Izm和SHRch1_18的Hmgb 1和Prx 2 mRNA表达均高于WKY/Izm。与WKY/Izm相比，SHR/Izm中AVP的Tlr2表达减少。SHRpch1_18在AVP + H/R后Hmgb 1表达增加。AVP调节的Hmgb1蛋白的表达减少了添加抗氧化剂N-乙酰半胱氨酸（NAC）。这些结果表明，AVP的氧化应激增强了星形胶质细胞中Hmgb 1，Prx 2和Tlr 2的表达。我们推测AVP在H/R过程中对Hmgb 1的调节可能与SHRSP/Izm和SHRpch 1_18大鼠炎症和卒中的诱导有关。
Stroke-prone spontaneously hypertensive rats (SHRSP/Izm) develop severe hypertension and astrocytic oedema following ischaemic stimulation. During ischaemic stress high-mobility group box 1 (Hmgb1) expression in astrocytes is induced, and subsequently potentiates deterioration of the brain due to ischaemic injury, which manifests as both cerebral inflammation and astrocytic oedema. Arginine vasopressin (AVP) induces brain injury and increases astrocytic swelling. After stroke, Hmgb1 and peroxiredoxin (Prx) are released at different times and activate macrophages in the brain via Toll-like receptors (Tlr2s). The purpose of this study was to examine whether AVP and/or hypoxia and reoxygenation (H/R) contribute to Hmgb1 regulation following ischaemic stroke. Thus, Hmgb1, Prx2 and Tlr2 expression levels in astrocytes isolated from Wistar Kyoto rats (WKY/Izm), spontaneously hypertensive rats (SHR/Izm), SHRSP/Izm and congenic rat strain SHRpch1_18 treated with AVP and/or H/R were compared. Gene and protein expression levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative PCR, and Western blot. mRNA expression of Hmgb1, Prx2 and Tlr2 induced by AVP was dose-dependent, and Hmgb1 and Prx2 expression was higher in SHR/Izm, SHRSP/Izm and SHRch1_18 than in WKY/Izm. Tlr2 expression with AVP was reduced in SHR/Izm compared to WKY/Izm. In SHRpch1_18, Hmgb1 expression increased after AVP plus H/R. AVP-modulated expression of Hmgb1 protein was reduced by the addition of the antioxidant N-acetylcysteine (NAC). These results suggest that oxidative stress by AVP enhanced expression of Hmgb1, Prx2 and Tlr2 in astrocytes. We hypothesize that regulation of Hmgb1 by AVP during H/R might be related to induction of inflammation and stroke in SHRSP/Izm and SHRpch1_18 rats.