Department of Perioperative Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
Anesthesiology. 2011 May;114(5):1190-9. doi: 10.1097/ALN.0b013e318212515b.
Previous studies suggest that the transient receptor potential vanilloid 1 (TRPV1) channel has a role in sepsis, but it is unclear whether its effect on survival and immune response is beneficial or harmful.
We studied the effects of genetic (Trpv1-knockout vs. wild-type [WT] mice) and pharmacologic disruption of TRPV1 with resiniferatoxin (an agonist) or capsazepine (an antagonist) on mortality, bacterial clearance, and cytokine expression during lipopolysaccharide or cecal ligation and puncture-induced sepsis.
After cecal ligation and puncture, genetic disruption of TRPV1 in Trpv1-knockout versus WT mice was associated with increased mortality risk (hazard ratio, 2.17; 95% CI, 1.23-3.81; P = 0.01). Furthermore, pharmacologic disruption of TRPV1 with intrathecal resiniferatoxin, compared with vehicle, increased mortality risk (hazard ratio, 1.80; 95% CI, 1.05-3.2; P = 0.03) in WT, but not in Trpv1-knockout, mice. After lipopolysaccharide, neither genetic (Trpv1 knockout) nor pharmacologic disruption of TRPV1 with resiniferatoxin had significant effect on survival compared with respective controls. In contrast, after lipopolysaccharide, pharmacologic disruption of TRPV1 with capsazepine, compared with vehicle, increased mortality risk (hazard ratio, 1.92; 95% CI, 1.02-3.61; P = 0.04) in WT animals. Furthermore, after cecal ligation and puncture, increased mortality in resiniferatoxin-treated WT animals was associated with higher blood bacterial count (P = 0.0004) and higher nitrate/nitrite concentrations and down-regulation of tumor necrosis factor α expression (P = 0.004) compared with controls.
Genetic or pharmacologic disruption of TRPV1 can affect mortality, blood bacteria clearance, and cytokine response in sepsis in patterns that may vary according to the sepsis-inducing event and the method of TRPV1 disruption.
先前的研究表明，瞬时受体电位香草酸 1（TRPV1）通道在脓毒症中起作用，但尚不清楚其对存活和免疫反应的影响是有益还是有害。
我们研究了遗传（TRPV1 敲除与野生型 [WT] 小鼠）和药理学破坏 TRPV1 对脂多糖或盲肠结扎和穿刺诱导的脓毒症期间死亡率、细菌清除率和细胞因子表达的影响，使用的方法为使用树脂毒素（激动剂）或辣椒素（拮抗剂）。
盲肠结扎和穿刺后，TRPV1 敲除与 WT 小鼠相比，TRPV1 基因敲除与更高的死亡率风险相关（风险比，2.17；95%置信区间，1.23-3.81；P=0.01）。此外，与载体相比，鞘内给予树脂毒素破坏 TRPV1 与 WT 小鼠而不是 Trpv1 敲除小鼠的死亡率风险增加（风险比，1.80；95%置信区间，1.05-3.2；P=0.03）。脂多糖后，与相应对照相比，TRPV1 的遗传（TRPV1 敲除）或药理学破坏对生存均无显著影响。相反，脂多糖后，与载体相比，用辣椒素破坏 TRPV1 与 WT 动物的死亡率风险增加（风险比，1.92；95%置信区间，1.02-3.61；P=0.04）。此外，盲肠结扎和穿刺后，与对照组相比，在 WT 动物中，用树脂毒素治疗后死亡率增加与血液细菌计数升高（P=0.0004）和硝酸盐/亚硝酸盐浓度升高以及肿瘤坏死因子 α 表达下调有关（P=0.004）。
TRPV1 的遗传或药理学破坏可以影响脓毒症中的死亡率、血液细菌清除率和细胞因子反应，其模式可能根据脓毒症诱导事件和 TRPV1 破坏方法而有所不同。
