Gao Hong-Kai, Zhou Zong-Guang, He Tao, Chen You-Qin, Han Fang-Hai, Wang Cun
Department of General Surgery & Division of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Hepatobiliary Pancreat Dis Int. 2004 May;3(2):311-5.
Traditional Chinese medicine is a potent agent in the management of clinical and experimental acute pancreatitis (AP), but the molecular mechanism of its therapeutic action is unclear. Numerous experimental and clinical studies have shown that platelet endothelial cell adhesion molecule-1 (PECAM-1) is pivotal to leukocyte recruitment, which results in microcirculatory injury during inflammation, but its role in acute pancreatitis is poorly understood. We investigated the effects of a compound of traditional Chinese medicine pancreatitis-1 (TCMP-1) on the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in acute edematous pancreatitis (AEP).
The model of acute pancreatitis was established by subcutaneous injection of caerulein, and TCMP-1 treated groups were given TCMP-1 by catheterization from mouth to stomach (20 ml/kg) immediately after first time subcutaneous injection of caerulein. The changes of expression of PECAM-1 on leukocytes from the blood of the splenic vein and inferior vena cava were determined by flow cytometry.
In the AEP group, expression of PECAM-1 on PMNs was not significantly different between pancreatic microcirculation and systemic circulation at AEP2h and AEP4h time point. Then from AEP4h time point to AEP8h time point, expression of PECAM-1 was up-regulated in systemic circulation while it was down-regulated in pancreatic microcirculation and was significantly different between pancreatic microcirculation and systemic circulation at AEP8h time point (P<0.05). In the TCMP-1 treated group, compared with the AEP group, expression of PECAM-1 on PMNs decreased in different levels between pancreatic microcirculation and systemic circulation and was of significant difference at AEP8h time point (P<0.05).
Inhibition of PECAM-1 expression on PMNs may prevent PMNs from transmigration through the endothelium and may be one of the treatment mechanisms of TCMP-1 decoction on AEP.
中药是临床和实验性急性胰腺炎(AP)治疗中的一种有效药物,但其治疗作用的分子机制尚不清楚。大量实验和临床研究表明,血小板内皮细胞黏附分子-1(PECAM-1)对白细胞募集至关重要,这会导致炎症期间的微循环损伤,但其在急性胰腺炎中的作用了解甚少。我们研究了中药复方胰腺炎-1(TCMP-1)对急性水肿性胰腺炎(AEP)中多形核白细胞(PMN)上血小板内皮细胞黏附分子-1(PECAM-1)表达变化的影响。
通过皮下注射雨蛙素建立急性胰腺炎模型,首次皮下注射雨蛙素后立即经口胃管注入TCMP-1(20 ml/kg)对TCMP-1治疗组进行给药。采用流式细胞术检测脾静脉和下腔静脉血液中白细胞上PECAM-1的表达变化。
在AEP组,AEP2h和AEP4h时间点,胰腺微循环和体循环中PMN上PECAM-1的表达无显著差异。然后从AEP4h时间点到AEP8h时间点,体循环中PECAM-1表达上调,而胰腺微循环中PECAM-1表达下调,在AEP8h时间点胰腺微循环和体循环之间存在显著差异(P<0.05)。在TCMP-1治疗组中,与AEP组相比,胰腺微循环和体循环中PMN上PECAM-1的表达在不同水平下降,在AEP8h时间点有显著差异(P<0.05)。
抑制PMN上PECAM-1的表达可能会阻止PMN穿过内皮迁移,这可能是TCMP-1水煎剂治疗AEP的机制之一。