Dembiński A, Warzecha Z, Konturek P C, Ceranowicz P, Stachura J, Tomaszewska R, Konturek S J
Department of Physiology, Collegium Medicum, Jagiellonian University, 16 Grzegórzecka street, 31-531, Kraków, Poland.
Eur J Pharmacol. 2000 Jun 9;398(1):159-68. doi: 10.1016/s0014-2999(00)00301-0.
We examined the influence of endogenous and exogenous epidermal growth factor (EGF) on pancreatic repair after acute pancreatitis. Caerulein-induced pancreatitis was evoked in rats with intact or removed salivary glands and EGF (10 microg/kg) was administered starting 24 h after cessation of caerulein infusion. The dose of EGF 10 microg/kg was chosen because it was the most effective in preliminary experiments when 1, 10 or 50 microg/kg of EGF was used. Caerulein administration caused acute edematous pancreatitis with biochemical and histological manifestation of pancreatic damage, followed by spontaneous regeneration. The effect of salivectomy on the course of acute pancreatitis was slight, resulting in additional reduction in pancreatic blood flow, DNA synthesis and in an increase in plasma interleukin 1beta level. Treatment with EGF accelerated the healing of pancreatic damage, causing an increase in pancreatic blood flow and DNA synthesis. EGF caused faster normalization of plasma amylase and lipase activity and plasma interleukin 1beta concentration, as well as, this peptide accelerated the restoration of pancreatic amylase activity. On histological examination, EGF caused reduction of pancreatic damage and acceleration of tissue repair. We conclude that EGF reduces the severity of pancreatic damage evoked by caerulein-induced pancreatitis-related pancreatic damage and accelerates tissue repair. The beneficial effects of EGF appear to depend, at least in part, on the improvement of pancreatic blood flow, as well as on an increase of pancreatic cell growth and limitation of the activation cytokine release.
我们研究了内源性和外源性表皮生长因子(EGF)对急性胰腺炎后胰腺修复的影响。在唾液腺完整或切除的大鼠中诱发蛙皮素诱导的胰腺炎,并在蛙皮素输注停止后24小时开始给予EGF(10微克/千克)。选择10微克/千克的EGF剂量是因为在初步实验中,当使用1、10或50微克/千克的EGF时,该剂量最有效。给予蛙皮素导致急性水肿性胰腺炎,并伴有胰腺损伤的生化和组织学表现,随后是自发再生。唾液腺切除对急性胰腺炎病程的影响轻微,导致胰腺血流量、DNA合成进一步减少,血浆白细胞介素1β水平升高。EGF治疗加速了胰腺损伤的愈合,导致胰腺血流量和DNA合成增加。EGF使血浆淀粉酶和脂肪酶活性以及血浆白细胞介素1β浓度更快恢复正常,并且这种肽加速了胰腺淀粉酶活性的恢复。组织学检查显示,EGF减轻了胰腺损伤并加速了组织修复。我们得出结论,EGF降低了蛙皮素诱导的胰腺炎相关胰腺损伤所引起的胰腺损伤的严重程度,并加速了组织修复。EGF的有益作用似乎至少部分取决于胰腺血流量的改善,以及胰腺细胞生长的增加和激活细胞因子释放的限制。