Wang X-Y, Tang Q-Q, Zhang J-L, Fang M-Y, Li Y-X
Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China.
Eur Rev Med Pharmacol Sci. 2014;18(3):338-43.
This study aimed to investigate the effect of SB203580 which is the inhibitor of p38 mitogen-activated protein kinase on pathologic change of pancreatic tissue and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1b) in rats with severe acute pancreatitis (SAP), Hematoxylin-eosin (HE) staining and immunohistochemistry were carried out in the present study.
Forty-five male Wistar rats were divided into three groups: the SAP group (N=15), SB203580-treated group (SB group) (N=15), and the control group (N=15). Severe acute pancreatitis was induced by injection of sodium taurocholate into the pancreatic duct. For SB203580-treated group, SB203580 were administered via intraperitoneal injection (10 mg/kg). Serum amylase activity was measured 6, 12 and 24 hours respectively after the operation. The pancreas tissue were stained with HE for histopathological evaluation and the expression of TNF-α and IL-1b in the pancreatic tissue were determined through inferior vena cava.
The results show that the level of amylase in SAP group was higher than that in the other groups. Further, the pancreas tissues of SB group rats were observed more mildly edematous, hemorrhagic and with monocytes infiltration. Based on immunohistochemical staining, the expression of TNF-α and IL-1β in SAP rats were significantly increased than those of the control group. However, those of SB203580-treated group were more significantly reduced than those of SAP group (p < 0.05).
Those data suggest that SB203580, down regulating the expression of pro-inflammatory mediators such as TNF-α and IL-1β, then through p38 MAPK signaling pathway inhibition, plays an important role in the treatment of SAP.
本研究旨在探讨p38丝裂原活化蛋白激酶抑制剂SB203580对重症急性胰腺炎(SAP)大鼠胰腺组织病理变化及肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)表达的影响,本研究采用苏木精-伊红(HE)染色和免疫组织化学方法。
45只雄性Wistar大鼠分为三组:SAP组(N = 15)、SB203580治疗组(SB组)(N = 15)和对照组(N = 15)。通过向胰管注射牛磺胆酸钠诱导重症急性胰腺炎。对于SB203580治疗组,通过腹腔注射给予SB203580(10mg/kg)。分别在术后6、12和24小时测量血清淀粉酶活性。胰腺组织用HE染色进行组织病理学评估,并通过下腔静脉测定胰腺组织中TNF-α和IL-1β的表达。
结果显示,SAP组淀粉酶水平高于其他组。此外,观察到SB组大鼠的胰腺组织水肿、出血较轻,单核细胞浸润较少。基于免疫组织化学染色,SAP大鼠中TNF-α和IL-1β的表达明显高于对照组。然而,SB203580治疗组的表达比SAP组更显著降低(p < 0.05)。
这些数据表明,SB203580通过抑制p38丝裂原活化蛋白激酶信号通路,下调TNF-α和IL-1β等促炎介质的表达,在SAP的治疗中起重要作用。