牛磺熊去氧胆酸对急性胰腺炎大鼠内质网应激蛋白的影响  

Regulation of tauroursodeoxycholic acid on the expression of reticulum-related stress protein in rats with acute pancreatitis

作　　者：吴遥[1,2] 刘学政[2] 

机构地区：[1]辽宁医学院附属第一医院,辽宁锦州121000 [2]辽宁医学院,辽宁锦州121000

出　　处：《现代预防医学》2016年第6期1075-1080,共6页Modern Preventive Medicine

基　　金：国家自然科学基金主任基金(31140072);辽宁省自然科学基金计划(20102138)

摘　　要：目的观察牛磺熊去氧胆酸(TUDCA)对蛙皮素诱导的急性胰腺炎大鼠内质网应激相关蛋白GRP78/BIP、s XBP-1、pJNK及Caspase-12表达的影响,探讨其对急性胰腺炎保护作用的机制。方法 3月龄SD大鼠96只,随机分为Na Cl对照组、TUDCA对照组、CER组、TUDCA治疗组,每组24只。于造模成功后的第0.5、1、2、4 h取胰腺组织,采用常规HE染色法观察各组大鼠胰腺组织学改变;应用免疫蛋白印迹法检测GRP78/BIP、s XBP-1、pJNK及Caspase-12蛋白的表达情况。结果 CER组、TUDCA治疗组均出现炎症反应及凋亡形态学改变,而TUDCA治疗组反应较轻。诱导后各时间点CER组GRP78/BIP呈上升趋势;TUDCA治疗组较比CER组表达降低(P<0.05),但仍高于Na Cl对照组。CER组s XBP-1在诱导后1 h、2 h表达增加,与TUDCA治疗组比较,差异有统计学意义(P<0.05)。CER组、TUDCA治疗组pJNK的表达于0.5 h达到峰值,其后呈下降趋势,但仍显著高于Na Cl对照组、TUDCA对照组(P<0.05),TUDCA治疗组pJNK水平较CER组降低,在时间点2 h、4 h的表达差异有统计学意义(P<0.05)。CER组Caspase-12的表达增加,于2 h达到峰值。TUDCA治疗组与CER组比较,Caspase-12的表达降低,在时间点0.5 h、1 h、2 h差异有统计学意义(P<0.05)。结论 TUDCA通过下调GRP78/BIP、s XBP-1,抑制pJNK、Caspase-12表达,发挥其对大鼠急性胰腺炎的细胞保护潜能。Objective The aim of this study was to investigate the effects of taurocholate ursodeoxycholic acid（ TUDCA） on the expressing of endoplasmic reticulum stress- related proteins GRP78 / BIP,s XBP- 1,pJNK and Caspase- 12 in the established rats model with acute pancreatitis within bombesin in order to explore the mechanism of the protective effect against acute pancreatitis. Methods Each group was observed using conventional HE staining in rat pancreatic histological section of pancreas tissue by 0. 5,1,2,and 4 h after successful modeling. Western blot assays were applied to detect the expression of GRP78 / BIP,s XBP- 1,pJNK and Caspase- 12. Results CER group and TUDCA treatment group had inflammatory response and morphological changes of apoptosis,while the response of TUDCA treatment group was mild. The expression of GRP78 / BIP in CER group was increased at different time points after induction. TUDCA therapy group was lower than CER group（ P〈0. 05）,but was still higher than Na Cl control group. The expression of s XBP- 1 in CER group was increased after induction of 1h and 2h. Compared with TUDCA treatment group,the difference was statistically significant（ P〈0. 05）. The expression of pJNK in CER group and TUDCA treatment group reached a peak at the point of 0. 5h,then followed by a downward trend,but was still significantly higher than Na Cl control group and TUDCA control group（ P〈0. 05）. The expression of pJNK in TUDCA treatment group was decreased at the point of 2h and 4h compared with CER group. The difference of expression was statistically significant（ P〈0. 05）. The expression of Caspase- 12 in CER group was increased,peaked at the point of 2h. The expression of Caspase- 12 in TUDCA treatment group was reduced compared with CER group.The difference was statistically significant at the point of 0. 5h,1h,and 2h（ P〈0. 05）. Conclusion TUDCA has the potential cytoprotective effect in acute pancreatitis through reducing the expression of GRP78 / BIP and s XBP- 1 as well as inh

关 键 词：牛磺熊去氧胆酸 急性胰腺炎 GRP78/BIP XBP-1 pJNK CASPASE-12 

分 类 号：R576[医药卫生—消化系统]