The pancreas as a source of cardiovascular cell activating factors
The pancreas as a source of cardiovascular cell activating factors
复制标题
DOI：
10.1038/sj.mn.7300105
复制
发表时间：
2000-06-01
期刊：
影响因子：
2.4
通讯作者：
Schmid-Schönbein, GW
中科院分区：
文献类型：
--
作者：
Kistler, EB;Hugli, TE;Schmid-Schönbein, GW
目的：生理性休克导致激活循环白细胞和内皮细胞的血浆因子水平升高，从而损害微血管功能。这些血浆衍生活化剂的性质和来源尚不清楚。为了研究这些因素的可能来源，我们匀浆大鼠内脏器官，并测定其在体内和体外对心血管细胞的活性，in vitro.Methods：新鲜组织样品从小肠，脾脏，心脏，肝脏，肾脏，肾上腺，胰腺匀浆。他们的能力，诱导白细胞伪足的形成和硝基四氮唑蓝（NBT）的减少进行了测试，并在体内对血压，生存，和微血管细胞损伤的影响examined.Results：一个显着增加（p < 0.001），白细胞活化与对照组相比，观察到胰腺匀浆，但没有与其他器官的匀浆。白细胞激活诱导的其他组织的匀浆，只有在预先孵育与胰腺匀浆的亚刺激浓度。胰腺丝氨酸蛋白酶、胰蛋白酶和胰凝乳蛋白酶：不刺激白细胞，也产生其他组织的活性。在组织匀浆过程中加入丝氨酸蛋白酶抑制剂6-脒基-2-萘基对胍基苯甲酸二甲磺酸盐（ANGD）可显著抑制白细胞伪足的形成（p < 0.001）。向大鼠注射胰腺匀浆导致血浆过氧化氢水平升高，平均动脉压瞬时下降，这通常是致命的。这些反应被预先输注ANGD预防（p < 0.001）。大鼠肠系膜的活体显微镜检查证实，过滤的胰腺匀浆的灌流导致细胞死亡的显著增加（p < 0.05）;如通过碘化丙啶和过氧化氢形成检测的（p < 0.05），如通过二氯荧光素二乙酸酯（DCFH）荧光测定的。这些结果表明，胰腺酶攻击组织并产生与休克时器官功能障碍相关的细胞激活剂。
Objective: Physiological shock leads to elevated levels of plasma factors that activate circulating leukocytes and endothelial cells, thereby compromising microvascular functions. The nature and source of these plasma-derived activators are unknown. To examine the possible origin of these factors, we homogenized rat internal organs and measured their activity on cardiovascular cells in vivo and in vitro.Methods: Fresh tissue samples from small intestine, spleen, heart, liver, kidney, adrenals, and pancreas were homogenized. Their ability to induce leukocyte pseudopod formation and nitroblue tetrazolium (NBT) reduction was tested and their impact in vivo on blood pressure, survival, and microvascular cell injury was examined.Results: A dramatic increase (p < 0.001) in leukocyte activation compared to controls was observed with pancreas homogenate but not with homogenates from the other organs. Leukocyte activation was induced by homogenates of other tissues only after prior incubation with substimulatory concentrations of pancreatic homogenate. Pancreatic serine proteases, trypsin and chymotrypsin: which did not stimulate leukocytes, also generated activity from other tissues. Leukocyte pseudopod formation could be significantly inhibited by adding the serine protease inhibitor 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (ANGD) during tissue homogenization (p < 0.001). Injection of pancreatic homogenate into rats led to increased plasma hydrogen peroxide levels and an instantaneous drop in mean arterial pressure that was often lethal. These responses were prevented by prior infusion of ANGD (p < 0.001). Intravital microscopy of the rat mesentery confirmed that superfusion of filtered pancreatic homogenate leads to significant increases in cell death (p < 0.05); as detected by propidium iodide, and hydrogen peroxide formation (p < 0.05), as determined by dichlorofluorescein diacetate (DCFH) fluorescence.Conclusion: These results suggest that pancreatic enzymes attack tissue and generate cellular activators that are associated with organ dysfunction in shock.