Qiu Lei, Yin Guojian, Cheng Li, Fan Yuting, Xiao Wenqin, Yu Ge, Xing Miao, Jia Rongrong, Sun Ruiqing, Ma Xiuying, Hu Guoyong, Wang Xingpeng, Tang Maochun, Zhao Yan
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai 200080, P.R. China.
Int J Mol Med. 2015 Mar;35(3):625-36. doi: 10.3892/ijmm.2015.2070. Epub 2015 Jan 16.
This study aimed to investigate the effects of astragaloside IV (AS-IV; 3-O-β-D-xylopyranosyl-6-O‑β-D-glucopyranosylcycloastragenol), which has been reported to have comprehensive pharmacological functions, on sodium taurocholate (NaTc)/L-arginine (L-Arg)-induced acute pancreatitis (AP) in rats in vivo and in rat pancreatic acinar cells in vitro. NaTc-induced experimental AP was induced in rats by injecting 4% NaTc (0.1 ml/100 g) in the retrograde direction of the biliopancreatic duct. L-Arg-induced experimental AP was induced in rats by 2 intraperitoneal injections of 20% L-arg (3 g/kg), with an interval of 1 h between the injections. The rats were pre-treated AS-IV (50 mg/kg) or the vehicle (DMSO) 2 h prior to the induction of AP. Enzyme-linked immunosorbent assay, H&E staining, myeloperoxidase (MPO) activity, reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry were used to evaluate the effects of AS-IV on AP. The results revealed that treatment with AS-IV significantly reduced serum amylase and lipase levels, pancreatic pathological alterations, the secretion of pro-inflammatory cytokines, MPO activity, and the protein expression of nuclear factor-κB (NF-κB) in vivo. Moreover, pre-treatment with AS-IV significantly increased the expression levels of manganese superoxide dismutase and cuprum/zinc superoxide dismutase. In the in vitro experiment, treatment of the cells with AS-IV aslo reduced rat pancreatic acinar cell necrosis and nuclear NF-κB activity, and enhanced the protein expression of superoxide dismutase. In conclusion, this study indicates that the protective effects of AS-IV on experimental AP in rats may be closely related to the inhibition of NF-κB. In addition, our results indicate that AS-IV may exert potential antioxidant effects on AP. Therefore, AS-IV may be an effective therapeutic agent for AP.
本研究旨在探讨已报道具有多种药理功能的黄芪甲苷IV(AS-IV;3-O-β-D-吡喃木糖基-6-O-β-D-吡喃葡萄糖基环黄芪醇)对牛磺胆酸钠(NaTc)/L-精氨酸(L-Arg)诱导的大鼠体内急性胰腺炎(AP)以及体外大鼠胰腺腺泡细胞的影响。通过在胆胰管逆行方向注射4% NaTc(0.1 ml/100 g)诱导大鼠发生NaTc诱导的实验性AP。通过给大鼠腹腔注射2次20% L-精氨酸(3 g/kg)诱导L-Arg诱导的实验性AP,两次注射间隔1小时。在诱导AP前2小时,大鼠预先接受AS-IV(50 mg/kg)或溶剂(二甲基亚砜)处理。采用酶联免疫吸附测定、苏木精-伊红染色、髓过氧化物酶(MPO)活性检测、逆转录-定量聚合酶链反应、蛋白质免疫印迹分析和免疫组织化学来评估AS-IV对AP的影响。结果显示,AS-IV处理显著降低了体内血清淀粉酶和脂肪酶水平、胰腺病理改变、促炎细胞因子分泌、MPO活性以及核因子-κB(NF-κB)的蛋白表达。此外,AS-IV预处理显著提高了锰超氧化物歧化酶和铜/锌超氧化物歧化酶的表达水平。在体外实验中,AS-IV处理细胞也减少了大鼠胰腺腺泡细胞坏死和核NF-κB活性,并增强了超氧化物歧化酶的蛋白表达。总之,本研究表明AS-IV对大鼠实验性AP的保护作用可能与抑制NF-κB密切相关。此外,我们的结果表明AS-IV可能对AP发挥潜在的抗氧化作用。因此,AS-IV可能是AP的一种有效治疗药物。