Olsson L E, Wheeler M A, Sessa W C, Weiss R M
Section of Urology, Yale University School of Medicine, New Haven, Connecticut, USA.
J Pharmacol Exp Ther. 1998 Mar;284(3):1203-8.
Systemic bacterial lipopolysaccharides (LPS) induce inflammatory responses characteristic of sepsis. Instillation of LPS into rat bladder produces a localized inflammatory response similar to that seen in urinary tract infections (UTIs). Four hours after intravesical instillation of LPS, neutrophils infiltrate into the bladder, and mRNA for inducible nitric oxide synthase (iNOS) and the cytokines, interleukin (IL)-6 and IL-10, is detected in rat bladder but not in the kidney. Induction of iNOS protein is inferred because urinary nitrate and cGMP levels are increased 4 hr after LPS intravesical instillation and remain elevated for at least 24 hr. When LPS is injected intraperitoneally, iNOS and IL-6 mRNA are induced both in the bladder and in the kidney. These data are consistent with the effects of intravesical instillation of LPS remaining localized, iNOS activity increases in both particulate and soluble bladder fractions when measured 4 hr after intravesical instillation of LPS. The magnitude of these increases in iNOS activity in the bladder is not as great as when LPS is injected intraperitoneally. Intravesical instillation of LPS induces no increase in lung or kidney NOS activity. The localized inflammatory response produced by intravesical instillation of LPS demonstrates the importance of LPS as a mediator of the host response in UTIs and supports the use of urinary measurements of nitrate and cGMP in humans as indicative of the localized induction of iNOS in UTIs.
全身性细菌脂多糖（LPS）可诱导脓毒症特有的炎症反应。将LPS注入大鼠膀胱会产生一种局部炎症反应，类似于在尿路感染（UTI）中所见的反应。膀胱内注入LPS 4小时后，中性粒细胞浸润到膀胱中，并且在大鼠膀胱而非肾脏中检测到诱导型一氧化氮合酶（iNOS）以及细胞因子白细胞介素（IL）-6和IL-10的mRNA。推断iNOS蛋白被诱导，因为膀胱内注入LPS 4小时后尿硝酸盐和cGMP水平升高，并至少持续升高24小时。当腹腔注射LPS时，膀胱和肾脏中均诱导出iNOS和IL-6 mRNA。这些数据与膀胱内注入LPS的作用局限一致，膀胱内注入LPS 4小时后测量时，膀胱微粒体和可溶性部分中的iNOS活性均增加。膀胱中iNOS活性的增加幅度不如腹腔注射LPS时大。膀胱内注入LPS不会导致肺或肾脏NOS活性增加。膀胱内注入LPS产生的局部炎症反应证明了LPS作为UTI中宿主反应介质的重要性，并支持将人体尿液中硝酸盐和cGMP的测量用作UTI中iNOS局部诱导的指标。
