Kihara Yasuyuki, Yoshikawa Hiroyuki, Honda Hidekazu, Fukumitsu Ken-ichirou, Yamaguchi Taizou, Otsuki Makoto
Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Pancreas. 2005 Jul;31(1):48-53. doi: 10.1097/01.mpa.0000168223.43709.28.
Group 2 phospholipase A2 (PLA2) plays an important role in the pathogenesis of multiple organ failure associated with acute pancreatitis. C57 BL/6J mice are natural group 2 PLA2 knockout mice lacking group 2 PLA2 mRNA. To clarify the role of group 2 PLA2 in the exacerbation of acute pancreatitis, we studied the biologic and histologic alterations in choline-deficient and ethionine-supplemented (CDE) diet-induced pancreatitis in group 2 PLA2-deficient C57 BL/6J mice and compared them with those in wild-type mice.
Female C57 BL/6J mice weighing 20 to 22 g were fed a CDE diet for 3 days to induce pancreatitis. Female C3H/HEJ mice were used as controls. Mice were killed on days 1, 2, and 3 after the onset of the CDE diet. The severity of pancreatitis was evaluated by survival rate, plasma PLA2 activity, serum amylase level, histologic changes in the pancreas and lung, and myeloperoxidase activity in the lung.
The survival rate of C57 BL/6J mice was 100% up to day 3 after the onset of the CDE diet, whereas that of the control mice was 42% on day 3. Plasma PLA2 activity in control mice increased on day 3 but did not increase in C57 BL/6J mice. Serum amylase activity on day 3 in C57 BL/6J mice was 15,480 +/- 3036 SU/dL, which was significantly lower than that in the control mice (43,760 +/- 8657 SU/dL, P < 0.01). Histologic changes in the pancreas of C57 BL/6J mice were markedly milder than in control mice. The degree of alveolar membrane thickening and infiltration of inflammatory cells in the lung of C57 BL/6J mice were overtly less than those of the controls. Myeloperoxidase activity in the lung of C57 BL/6J mice was lower, albeit insignificant, than in C3H/HEJ mice.
Natural disruption of the group 2 PLA2 gene protects against CDE diet-induced acute pancreatitis and associated lung injury. These findings support the view that group 2 PLA2 is one of the factors in the exacerbation of severe acute pancreatitis.
第2组磷脂酶A2（PLA2）在与急性胰腺炎相关的多器官功能衰竭发病机制中起重要作用。C57 BL/6J小鼠是缺乏第2组PLA2 mRNA的天然第2组PLA2基因敲除小鼠。为阐明第2组PLA2在急性胰腺炎加重中的作用，我们研究了第2组PLA2缺陷型C57 BL/6J小鼠在胆碱缺乏及补充乙硫氨酸（CDE）饮食诱导的胰腺炎中的生物学和组织学改变，并与野生型小鼠进行比较。
体重20至22 g的雌性C57 BL/6J小鼠喂食CDE饮食3天以诱导胰腺炎。雌性C3H/HEJ小鼠用作对照。在CDE饮食开始后的第1、2和3天处死小鼠。通过存活率、血浆PLA2活性、血清淀粉酶水平、胰腺和肺的组织学变化以及肺中的髓过氧化物酶活性评估胰腺炎的严重程度。
C57 BL/6J小鼠在CDE饮食开始后至第3天的存活率为100%，而对照小鼠在第3天的存活率为42%。对照小鼠的血浆PLA2活性在第3天增加，但C57 BL/6J小鼠未增加。C57 BL/6J小鼠在第3天的血清淀粉酶活性为15,480±3036 SU/dL，显著低于对照小鼠（43,760±8657 SU/dL，P<0.01）。C57 BL/6J小鼠胰腺的组织学变化明显比对照小鼠轻。C57 BL/6J小鼠肺中肺泡膜增厚程度和炎性细胞浸润明显少于对照小鼠。C57 BL/6J小鼠肺中的髓过氧化物酶活性低于C3H/HEJ小鼠，尽管差异不显著。
第2组PLA2基因的天然缺失可预防CDE饮食诱导的急性胰腺炎及相关肺损伤。这些发现支持第2组PLA2是重症急性胰腺炎加重因素之一的观点。
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