Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China.
PLoS One. 2012;7(7):e40160. doi: 10.1371/journal.pone.0040160. Epub 2012 Jul 2.
Severity of acute pancreatitis contributes to the modality of cell death. Pervious studies have demonstrated that the herb medicine formula "Dachengqi Decoction" (DCQD) could ameliorate the severity of acute pancreatitis. However, the biological mechanisms governing its action of most remain unclear. The role of apoptosis/necrosis switch within acute pancreatitis has attracted much interest, because the induction of apoptosis within injured cells might suppress inflammation and ameliorate the disease. In this study, we used cerulein (10(-8) M)-stimulated AR42J cells as an in vitro model of acute pancreatitis and retrograde perfusion into the biliopancreatic duct of 3.5% sodium taurocholate as an in vivo rat model. After the treatment of DCQD, cell viability, levels of apoptosis and necrosis, reactive oxygen species positive cells, serum amylase, concentration of nitric oxide and inducible nitric oxide syntheses, pancreatic tissue pathological score and inflammatory cell infiltration were tested. Pretreatment with DCQD increased cell viability, induced apoptosis, decreased necrosis and reduced the severity of pancreatitis tissue. Moreover, treatment with DCQD reduced the generation of reactive oxygen species in AR42J cells but increased the concentration of nitric oxide of pancreatitis tissues. Therefore, the regulation of apoptosis/necrosis switch by DCQD might contribute to ameliorating the pancreatic inflammation and pathological damage. Further, the different effect on reactive oxygen species and nitric oxide may play an important role in DCQD-regulated apoptosis/necrosis switch in acute pancreatitis.
急性胰腺炎的严重程度与细胞死亡方式有关。先前的研究表明,草药方剂“大承气汤”(DCQD)可改善急性胰腺炎的严重程度。然而,其作用的大多数生物学机制仍不清楚。急性胰腺炎中细胞凋亡/坏死开关的作用引起了广泛关注,因为在受损细胞中诱导细胞凋亡可能抑制炎症并改善疾病。在这项研究中,我们使用 10(-8) M 胆囊收缩素刺激的 AR42J 细胞作为急性胰腺炎的体外模型,并将 3.5%牛磺胆酸钠逆行灌注到胰胆管作为体内大鼠模型。用 DCQD 处理后,检测细胞活力、凋亡和坏死水平、活性氧阳性细胞、血清淀粉酶、一氧化氮浓度和诱导型一氧化氮合成酶、胰腺组织病理评分和炎症细胞浸润。DCQD 的预处理增加了细胞活力,诱导了细胞凋亡,减少了坏死,并减轻了胰腺炎组织的严重程度。此外,DCQD 处理减少了 AR42J 细胞中活性氧的产生,但增加了胰腺炎组织中一氧化氮的浓度。因此,DCQD 调节细胞凋亡/坏死开关可能有助于改善胰腺炎症和病理损伤。此外,对活性氧和一氧化氮的不同作用可能在 DCQD 调节急性胰腺炎中的细胞凋亡/坏死开关中发挥重要作用。