Department of Surgery, Technische Universität München, Munich, Germany.
Pancreatology. 2011;11(1):57-67. doi: 10.1159/000325972. Epub 2011 Apr 8.
BACKGROUND/AIMS: Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP.
To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 μg/kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation.
Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels.
Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP. and IAP.
背景/目的:急性胰腺炎(AP)的特征是过早的酶原激活、全身性炎症反应导致炎症浸润、持续的细胞内钙、神经源性炎症和疼痛。抑制性神经递质和细胞保护氨基酸甘氨酸对炎症细胞具有直接抑制作用,抑制钙内流和神经元激活,因此代表了 AP 的一种潜在治疗剂。
为了探讨甘氨酸的影响,通过超最大剂量的 cerulein 刺激(10 μg/kg BW/h)诱导大鼠轻度 AP,通过逆行注射 3%牛磺胆酸钠溶液到共同胆胰管诱导大鼠重度 AP。在 AP 诱导前,静脉内给予 100/300 mmol 甘氨酸。为了阐明甘氨酸对 AP 的作用,我们测定了病理形态学、胰腺细胞因子以及蛋白酶、血清脂肪酶和淀粉酶、胰腺和肺 MPO 活性以及疼痛感觉。
甘氨酸的给药导致 AP 的病理形态学改变明显改善,例如 cerulein 性胰腺炎中坏死、炎症浸润和细胞质空泡减少。在牛磺胆酸钠性胰腺炎中,甘氨酸还降低了胰腺细胞因子和 MPO 活性以及血清脂肪酶和淀粉酶水平。
甘氨酸通过减轻胰内和全身炎症反应减轻了轻度和更严重的 AP 的严重程度。因此,甘氨酸似乎是预防治疗 AP 和 IAP 的有前途的工具。