Coşkun T, Alican I, Yeğen B C, San T, Cetinel S, Kurtel H
Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
Digestion. 1995;56(3):214-9. doi: 10.1159/000201246.
The objective of this study was to determine the role of cyclosporin A (CsA) on cold-restraint-induced gastric lesions. Animals were subjected to 3 h immobilization at 4 degrees C in plastic restraining devices following a starvation period of 48 h. Gastric samples were obtained for the measurement of myeloperoxidase (MPO) activity, an index of number of peroxidase positive cells and thiobarbituric acid-reactive substances (TBARS; lipid peroxidation). Animals were pretreated with CsA which is a potent immunosuppressant and inhibits ischemia/reperfusion-induced polymorphonuclear leukocyte (PMN) infiltration. Cold-restraint administration significantly elevated the tissue MPO activity and TBARS formation. CsA pretreatment significantly reduced the severity of cold-restraint-induced gastric lesions while attenuating the elevated MPO measurements observed during cold-restraint administration. Animals rendered neutropenic with antineutrophil serum (ANS) exhibited significantly less gastric mucosal injury normally observed after cold-restraint stress. Neither CsA nor ANS treatment effected the elevated TBAR levels, indicating that PMNs are not involved in the lipid peroxidation process observed after cold-restraint stress. In conclusion, the results of this study indicate that CsA is capable of inhibiting cold-restraint-induced gastric mucosal injury and can attenuate the cold-restraint-induced increases in gastric MPO measurements. Our results also indicate that PMNs may be the important mediators of cold-restraint-induced gastric lesions.
本研究的目的是确定环孢素A（CsA）在冷束缚诱导的胃损伤中的作用。在48小时饥饿期后，将动物置于4摄氏度的塑料束缚装置中固定3小时。获取胃样本以测量髓过氧化物酶（MPO）活性，这是过氧化物酶阳性细胞数量的指标以及硫代巴比妥酸反应性物质（TBARS；脂质过氧化）。动物用CsA进行预处理，CsA是一种强效免疫抑制剂，可抑制缺血/再灌注诱导的多形核白细胞（PMN）浸润。冷束缚给药显著提高了组织MPO活性和TBARS形成。CsA预处理显著降低了冷束缚诱导的胃损伤的严重程度，同时减弱了冷束缚给药期间观察到的MPO测量值的升高。用抗中性粒细胞血清（ANS）使动物中性粒细胞减少后，其胃黏膜损伤明显少于冷束缚应激后通常观察到的情况。CsA和ANS处理均未影响升高的TBAR水平，表明PMN不参与冷束缚应激后观察到的脂质过氧化过程。总之，本研究结果表明CsA能够抑制冷束缚诱导的胃黏膜损伤，并能减弱冷束缚诱导的胃MPO测量值的增加。我们的结果还表明，PMN可能是冷束缚诱导的胃损伤的重要介质。
