在氧化应激诱导胰腺损伤的大鼠中，柳氮磺胺吡啶通过核因子κB信号通路抑制胰腺炎症和纤维化形成。
Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-κB signaling pathway in rats with oxidative stress-induced pancreatic injury.
作者信息
Wang Ya-Ru, Tian Fei-Long, Yan Ming-Xian, Fan Jin-Hua, Wang Li-Yun, Kuang Rong-Guang, Li Yan-Qing
机构信息
Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Shandong University School of Medicine, Qilu Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
出版信息
Drug Des Devel Ther. 2016 May 24;10:1743-51. doi: 10.2147/DDDT.S107679. eCollection 2016.
BACKGROUND
Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain.
PURPOSE
To investigate the effects of sulfasalazine (SF) on pancreatic inflammation and fibrogenesis.
METHODS
Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC) and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg) 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week); group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week); and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-κB pathway and fibrogenesis including NF-κB/p65, TNF-α, ICAM-1, α-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting.
RESULTS
Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-κB/p65, ICAM-1, and α-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse transcription polymerase chain reaction showed increased levels of NF-κB/p65, ICAM-1, TNF-α, α-SMA, and Con 1 mRNA in DDC and DS1 rats in comparison to normal controls. The mRNA levels of these molecules in DS2 and DS3 rats were significantly lower than those in DS1 and DDC rats. Western blotting demonstrated that the NF-κB/p65, ICAM-1, and α-SMA expressions in pancreatic tissues of the rats of the DDC group were more clear than those of the normal control, DS2, and DS3 rats.
CONCLUSION
SF inhibits pancreatic inflammation and fibrogenesis via NF-κB signaling pathway.
背景
慢性胰腺炎和胰腺纤维化的发病机制及有效治疗方法仍不明确。
目的
研究柳氮磺胺吡啶（SF）对胰腺炎症和纤维化形成的影响。
方法
用二乙基二硫代氨基甲酸盐（DDC）诱导大鼠发生慢性胰腺损伤，并通过腹腔注射SF进行干预。将大鼠分为五组：N组为正常对照组，大鼠仅用蒸馏水治疗；DS1组，大鼠在DDC治疗前2小时接受SF（10毫克/千克）；DS2组，大鼠先用DDC治疗，然后用SF（100毫克/千克，每周两次）；DS3组，大鼠先用DDC治疗，然后用SF（100毫克/千克，每周三次）；DDC组，大鼠仅用DDC治疗。通过苏木精-伊红染色和天狼星红染色来测定胰腺炎症和纤维化情况。通过免疫组织化学染色、逆转录聚合酶链反应和蛋白质印迹法检测与核因子κB（NF-κB）信号通路及纤维化形成相关的基因和蛋白，包括NF-κB/p65、肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）、α-平滑肌肌动蛋白（α-SMA）和Con 1。
结果
DDC组和DS1组大鼠在DDC治疗后组织学评分最高，但与DDC组相比，DS2组和DS3组的评分显著降低。天狼星红染色显示，DDC组和DS1组大鼠有明显的胶原形成，而DS2组和DS3组大鼠则没有。免疫组织化学显示，NF-κB/p65、ICAM-1和α-SMA在DDC组和DS1组大鼠中强烈表达，而DS2组和DS3组大鼠呈轻度至中度表达。逆转录聚合酶链反应显示，与正常对照组相比，DDC组和DS1组大鼠中NF-κB/p65、ICAM-1、TNF-α、α-SMA和Con 1的信使核糖核酸（mRNA）水平升高。DS2组和DS3组大鼠中这些分子的mRNA水平显著低于DS1组和DDC组大鼠。蛋白质印迹法表明，DDC组大鼠胰腺组织中NF-κB/p65、ICAM-1和α-SMA的表达比正常对照组、DS2组和DS3组大鼠更明显。
结论
SF通过NF-κB信号通路抑制胰腺炎症和纤维化形成。
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