Hypertriglyceridemia Aggravates ER Stress and Pathogenesis of Acute Pancreatitis
Hypertriglyceridemia Aggravates ER Stress and Pathogenesis of Acute Pancreatitis
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DOI：
10.5754/hge12042
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发表时间：
2012-10-01
影响因子：
--
通讯作者：
Ma, Jingjing
中科院分区：
文献类型：
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作者：
Zeng, Yue;Wang, Xingpeng;Ma, Jingjing
背景/目的：内质网(ER)应激和高甘油三酯血症(HTG)与急性胰腺炎(AP)有关。方法：在细胞模型中，大鼠外分泌腺泡细胞与棕榈酸(0.05或0.1 mmol/L，3h)预孵育，并用CCK-8(100pmol/L，30min)刺激。动物模型采用高脂饮食诱导大鼠HTG和AP模型，注射雨蛙素(20mgg/kg)。通过检测胰淀粉酶分泌、细胞内钙离子浓度、细胞凋亡率和组织学变化来评估胰腺细胞的损伤。用RT-PCR和免疫组织化学方法检测内质网应激诱导的未折叠蛋白反应(UPR)相关基因的表达。结果：在CCK-8刺激的大鼠腺泡细胞中，PA预孵育引起淀粉酶分泌增加，细胞内钙离子积聚时间延长，细胞凋亡率增加。高脂饮食的大鼠血清甘油三酯水平显著升高。AP的诱导导致高脂饮食组大鼠胰腺组织细胞凋亡率高于对照组。为支持HTG，UPR组分GRP78/Bip、XBP-1、GADD153/CHOP和caspase-12的表达上调。结论：当胰腺腺泡细胞中存在过多的脂肪酸时，AP发病的标志物和UPR组分水平升高。HTG似乎加重了内质网应激和AP的发病机制。
Background/Aims: Endoplasmic reticulum (ER) stress and hypertriglyceridemia (HTG) have been implicated in acute pancreatitis (AP). Methodology: For cellular model, rat exocrine acinar cells were preincubated with palmitic acid (0.05 or 0.1mmol/L, 3h) and stimulated with a cholecystokinin analog, CCK-8 (100pmol/L, 30min). For animal model, rats fed a high-fat diet to cause HTG and AP was induced by injection of caerulein (20 mu g/kg). Injury to pancreatic cells was estimated by measuring amylase secretion, intracellular calcium concentration, apoptosis and histological changes. Expression of genes involved in ER stress-induced unfolded protein response (UPR) was monitored by RT-PCR and immunohistology. Results: In CCK-8 stimulated rat acinar cells, preincubation with PA caused an increased secretion of amylase, a higher and prolonged accumulation of intracellular calcium and increased apoptosis. Rats on high-fat diet had significantly elevated serum triglyceride levels. Induction of AP led to increased apoptosis in pancreatic tissue on high-fat diet than controls. For favoring HTG, expression of UPR components, GRP78/Bip, XBP-1, GADD153/CHOP and caspase-12 was upregulated. Conclusions: Levels of markers of AP pathogenesis and components of UPR were elevated in the presence of excess fatty acids in pancreatic acinar cells. HTG appears to aggravate ER-stress and pathogenesis of AP.