MacMicking J D, Nathan C, Hom G, Chartrain N, Fletcher D S, Trumbauer M, Stevens K, Xie Q W, Sokol K, Hutchinson N
Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, New York 10021, USA.
Cell. 1995 May 19;81(4):641-50. doi: 10.1016/0092-8674(95)90085-3.
Mice deficient in inducible nitric oxide synthase (iNOS) were generated to test the idea that iNOS defends the host against infectious agents and tumor cells at the risk of contributing to tissue damage and shock. iNOS-/-mice failed to restrain the replication of Listeria monocytogenes in vivo or lymphoma cells in vitro. Bacterial endotoxic lipopolysaccharide (LPS) caused shock and death in anesthetized wild-type mice, but in iNOS-/-mice, the fall in central arterial blood pressure was markedly attenuated and early death averted. However, unanesthetized iNOS-/-mice suffered as much LPS-induced liver damage as wild type, and when primed with Propionobacterium acnes and challenged with LPS, they succumbed at the same rate as wild type. Thus, there exist both iNOS-dependent and iNOS-independent routes to LPS-induced hypotension and death.
为了验证诱导型一氧化氮合酶（iNOS）在保护宿主抵御感染因子和肿瘤细胞的同时会导致组织损伤和休克这一观点，研究人员培育出了iNOS基因缺陷的小鼠。iNOS基因敲除小鼠无法在体内抑制单核细胞增生李斯特菌的复制，也无法在体外抑制淋巴瘤细胞的生长。细菌内毒素脂多糖（LPS）可导致麻醉的野生型小鼠休克和死亡，但在iNOS基因敲除小鼠中，中心动脉血压的下降明显减弱，早期死亡得以避免。然而，未麻醉的iNOS基因敲除小鼠与野生型小鼠一样，都遭受了LPS诱导的肝脏损伤，并且在用痤疮丙酸杆菌致敏并接受LPS攻击时，它们的死亡率与野生型小鼠相同。因此，LPS诱导的低血压和死亡存在iNOS依赖和iNOS非依赖两种途径。
