Downregulation of GRP78 and XIAP is correlated with apoptosis during cerulein-induced acute pancreatitis in rats via regulation of caspase activation.

Downregulation of GRP78 and XIAP is correlated with apoptosis during cerulein-induced acute pancreatitis in rats via regulation of caspase activation.
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GRP78 和 XIAP 的下调通过调节 caspase 激活与雨蛙素诱导的大鼠急性胰腺炎期间的细胞凋亡相关

DOI:
10.3892/mmr.2012.1241
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发表时间:
2013-03
影响因子:
3.4
通讯作者:
Li Y
Li Y
中科院分区:
医学4区
文献类型:
--
作者:
Liu Y;Zhou ZG;Zhou B;Wang R;Yan H;Li Y

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本研究的目的是探讨78 kDa葡萄糖调节蛋白(GRP 78)和X连锁凋亡抑制蛋白(XIAP)在蛙皮素诱导的急性胰腺炎(CAP)细胞凋亡调控中的潜在作用。采用雨蛙肽(50 μg/kg)诱导大鼠CAP模型,通过检测血清淀粉酶和脂肪酶、胰腺水肿和组织学改变来评价CAP的严重程度。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测胰腺腺泡细胞凋亡,实时荧光定量PCR和Western blotting检测GRP 78、XIAP和凋亡基因caspase-3、-7和-9的表达。蛙皮素诱导CAP后,大鼠血清淀粉酶和脂肪酶升高,胰腺水肿,炎症和细胞凋亡。CAP大鼠海马GRP 78和XIAP的mRNA和蛋白水平均显著下调,caspase-3、-7和-9的mRNA水平及细胞凋亡指数均显著升高(P<0.05)。CAP中GRP 78、XIAP的表达与caspase的表达呈负相关(P<0.05)。这项研究表明,GRP 78和XIAP的下调与胰腺腺泡细胞的凋亡相关,这可能是通过在CAP过程中调节caspase的激活而发生的。
Our aim in the present study was to investigate the potential roles of the 78-kDa glucose-regulated protein (GRP78) and the X-linked inhibitor of apoptosis protein (XIAP) in the regulation of apoptosis during cerulein-induced acute pancreatitis (CAP). A rat CAP model was induced by injection of cerulein (50 μg/kg), and the severity of CAP was estimated by measuring serum amylase and lipase, pancreatic edema and histological changes. Pancreatic acinar cell apoptosis was determined by terminal-deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the expression of GRP78, XIAP and the apoptotic genes caspase-3, -7 and -9 were determined by real-time quantitative PCR and western blotting. After induction with cerulein, increased serum amylase and lipase, pancreatic edema, inflammation and apoptosis were observed in CAP rats. Furthermore, the mRNA and protein levels of GRP78 and XIAP were significantly downregulated in CAP rats, while the mRNA levels of caspase-3, -7 and -9, as well as the cell apoptotic index were markedly increased when compared with control rats (P<0.05). The expression of GRP78 and XIAP was negatively correlated with caspase expression in CAP (P<0.05). This study suggests that the downregulation of GRP78 and XIAP were correlated with apoptosis in pancreatic acinar cells, and that this may occur through the regulation of caspase activation during CAP.
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