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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 To observe the effect of TUDCA on the expression of endoplasmic reticulum stress-related proteins GRP78 / BIP, s XBP-1, pJNK and Caspase-12 in Bombescerin-induced acute pancreatitis Protection of acute pancreatitis mechanism. Methods Ninety-four-month-old SD rats were randomly divided into NaCl control group, TUDCA control group, CER group and TUDCA treatment group, with 24 rats in each group. Pancreatic tissues were harvested at 0.5, 1, 2 and 4 h after successful modeling. Histopathological changes of pancreas were observed by routine HE staining. GRP78 / BIP, s XBP-1, pJNK And Caspase-12 protein expression. Results Both inflammatory response and apoptotic morphological changes were observed in both CER and TUDCA treatment groups, but mild in TUDCA treatment group. After induction, GRP78 / BIP in CER group showed an upward trend at each time point. Compared with CER group, TUDCA treatment group decreased (P <0.05), but still higher than that of NaCl control group. The expression of XBP-1 in CER group increased at 1 h and 2 h after induction, which was significantly different from that in TUDCA group (P <0.05). The expression of pJNK in CER group and TUDCA group peaked at 0.5 h and then decreased, but still significantly higher than that in NaCl control group and TUDCA control group (P <0.05). The level of pJNK in TUDCA group was lower than that in CER group At 2 h, 4 h, there was a statistically significant difference (P <0.05). The expression of Caspase-12 increased in CER group and peaked at 2 h. Compared with CER group, the expression of Caspase-12 in TUDCA treatment group was lower than that in CER group (P <0.05) at the time points of 0.5 h, 1 h and 2 h. Conclusion TUDCA exerts its protective effect on acute pancreatitis in rats by down-regulating the expression of GRP78 / BIP, s XBP-1 and inhibiting the expression of pJNK and Caspase-12.