脓毒症肺损伤治疗冲辣椒素对TLR4-NF-κB通路的影响

Protective effects of capsaicine on lung injury in septic mice and its mechanism

目的探讨辣椒素受体(TRPV1)激动剂辣椒素在脓毒症肺损伤治疗中对TOLL受体(TLR)4-核因子(NF)-κB通路的影响。方法选取ICR小鼠108只,按随机数字表法分为6组:正常对照组(CON组)、辣椒素对照组(CAP+CON组)、TRPV1拮抗剂Capsazepine对照组(CAPZ+CON组)、脓毒症组(LPS组)、辣椒素组(CAP组)、Capsazepine组(CAPZ组)。LPS组、CAP组、CAPZ组均腹腔注射脂多糖(LPS)10mg/kg以制备LPS肺损伤模型,对照组经腹腔注射等量0.g%氯化钠溶液。造模前0.5hCAP组、CAP+CON组小鼠预先腹腔注射辣椒素,而CAPZ组、CAPZ+CON组小鼠则注射Capsazepine。每组取注射后3、8、16h等各时点检测肺组织NF-κB mRNA、TLR4 mRNA的表达量和肺组织含水量变化。结果与CON组比较,LPS组、CAP组、CAPZ组肺组织含水量在8、16h均有所上升(P<0.05);LPS组、CAP组、CAPZ组NF-κB mRNA、TLR4 mRNA在3、8、16h均表达增强(均P<0.05);与LPS组比较,CAP组肺组织含水量在8、16h均下降,NF-κB mRNA在8、16h均表达减弱(均P<0.05。结论 LPS肺损伤时TLR4 mRNA、NF-κB mRNA表达增强,肺组织含水量增加,辣椒素可能通过抑制NF-κB mRNA表达来减轻肺损伤,但对TLR4表达无影响。

Objective To investigate the protective effects of capsaicine on lung injury in septic mice and its mechanism. Methods One hundred and eight ICR male mice were randomly divided into six groups with 18 animals in each group. Septic model was induced by injection of lipopolysaccharide （LPS, 10mg/kg） in LPS, CAP and CAPZ groups;0.5h before LPS adminis-tration normal saline, capsaicine and capsazepine （TRPV1 antagonist） were injected intraperitoneal y respectively. For 3 control groups （CON, CAP＋CON and CAPZ＋CON groups）, normal saline, capsaicine and capsazepine were injected i.p , respectively. The expressions of NF- κB mRNA and TLR4mRNA were detected by RT- PCR at 3, 8 and 16h after injection and the histopatho-logical changes and lung water contents were also observed. Results Compared to CON group, the lung tissue water content was increased in LPS, CAP and CAPZ groups at 8 and 16h after injection; the expressions of NF- κBmRNA and TLR4mRNA were increased in LPS,CAP and CAPZ groups at 3, 8h and 16h （P〈0.05）. Compared to LPS group, the lung tissue water content and the expression of NF- κBmRNA were decreased in CAP group at 8h and 16h after injection （P〈0.05）. Conclusion Cap-saicine attenuates lung injury of septic mice, which is associated with up- regulated expression of NF- κBmRNA, but not with TLR4mRNA.