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氧应激在慢性胰腺损伤发生中的表达变化

The role of oxide stress during the pathogenesis of chronic pancreatic injuries induced by chronic high-fat diets in rat

摘要:

目的 探讨氧应激及脂质过氧化反应在慢性胰腺损伤和胰腺纤维化发病中表达的变化.方法 72只大鼠随机分为6组,每组12只,分别为正常对照组、2、4、6、10和16周高脂饮食组.建立长期高脂饮食诱导的胰腺损伤动物模型,观察胰腺组织形态学变化,检验模型;检测胰腺组织中脂质过氧化产物4-羟基-2,3-反式-丙烯醛(4-HNE)和血栓素A2受体的表达;应用免疫荧光双染色法测定α-平滑肌肌动蛋白(α-SMA)和4-HNE及α-SMA和血栓素A2受体在胰腺组织中的共表达.结果 长期高脂饮食诱导大鼠胰腺纤维化,胰腺星状细胞发生增殖和活化,免疫组化染色法测定胰腺组织中脂质过氧化产物4-HNE表达较正常组明显增加,血栓素A2受体在胰腺组织中表达也明显增加.免疫荧光双标染色法显示4-HNE和血栓素A2受体分别与α-SMA在胰腺组织中共表达.结论长期高脂饮食可以诱导胰腺慢性损伤,可能通过促进氧应激及脂质过氧化反应诱导大鼠胰腺星状细胞活化及胰腺纤维化.

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abstracts:

Objective To provide more detailed information on the roles of lipid peroxidation in the pathogenesis of chronic pancreatic injuries in a pre-clinical rat model.Methods Totally 72 rats were divided into 6 groups (12 in each group) Rats in 5 experimental groups (n =12) were fed with a high-fat diet (1% cholesterol,10% lard,0.3% sodium tauroglycocholate,87.3% standard rodent chow as the control group) for 2,4,6,10 and 16 weeks,respectively.Morphological studies in the pancreas tissue samples from rats were investigated by using various histological methods.Pancreatic stellate cells (PSCs)were identified by immunohistochemical staining for Desmin and α-smooth muscle actin (α-SMA).The expression of the lipid peroxidation was detected by immunostaining for 4-hydroxy-2-nonenal (4-HNE) and thromboxane A2 receptor (TxA2r).The co-localization of α-SMA and 4-HNE or α-SMA and TxA2r in PSCs was also analyzed in this study.Results Pancreatic cells with positive staining for Desmin and α-SMA in HFD rats were distributed in a more extensive way when compared to that in the control group.The levels of pancreatic 4-HNE and TxA2r were increased in rats from HFD groups significantly.The co-localization of 4-HNE and TxA2r were also found within activated PSCs in both of groups.Conclusion The results showed that a chronic HFD feeding may increase the lipid peroxidation process and collagen synthesis through a critical signaling pathway of activated PSCs following pancreatic injuries in rats.

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作者: 张小丽 [1] 李非 [1] 崔叶青 [1] 刘爽 [1] 孙海晨 [1]
第一作者: 张小丽
期刊: 《中华外科杂志》2012年50卷7期 646-649页 MEDLINEISTICPKUCSCD
分类号: R657.5
栏目名称: 论著
DOI: 10.3760/cma.j.issn.0529-5815.2012.07.019
发布时间: 2012-10-29
基金项目:
北京市自然科学基金资助项目
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