神经激肽1受体非肽类拮抗剂L-703,606对严重烫伤大鼠早期组织水肿的影响

目的观察神经激肽(NK)1受体非肽类拮抗剂L-703,606对严重烫伤大鼠早期组织水肿及血管通透性的影响。方法将152只SD大鼠随机分为正常对照组(8只),不作烫伤;烫伤对照组(48只),作20%TBSA深Ⅱ度烫伤;L-703,606组(48只)及β-七叶皂苷钠组(48只),分别从大鼠尾静脉注射250nmol/kg的L-703,606和1.8mg/kgβ-七叶皂苷钠,之后30min作20%TBSA深Ⅱ度烫伤。各致伤组大鼠创面伤后不予处理,并于烫伤后1、4、8、24、48、72h处死,取创周及肠组织标本待测,每组每时相点8只大鼠,并取正常对照组标本待测。用改良伊文思蓝渗出法及称取组织干湿重法测定各组大鼠创周和空肠组织血管通透性、组织含水量。结果伤后1h各致伤组大鼠创周及空肠组织血管通透性均较正常对照组增高(P<0.01),伤后4h开始逐渐下降。L-703,606组及β-七叶皂苷钠组创周组织血管通透性均低于烫伤对照组(P<0.01);伤后48、72h,L-703,606组高于β-七叶皂苷钠组(P<0.01).β-七叶皂苷钠组、L-703,606组空肠组织血管通透性伤后24h内低于烫伤对照组(P<0.01),β-七叶皂苷钠组伤后早期低于L-703,606组(P<0.01),伤后72h两组比较差异无统计学意义(P>0.05).组织含水量变化:伤后1h,各致伤组创周组织均呈现缺水状态,以后含水量逐渐升高,于伤后8~24h达峰值。伤后早期各致伤组空肠组织均出现一定的缺水状态,L-703,606组轻于烫伤对照组和β-七叶皂苷钠组(P<0.05或0.01),8h后表现出一定的水肿状态,伤后48h为甚,以L-703,606组水肿最轻,随后逐渐恢复。结论NK1受体非肽类拮抗剂L-703,606能降低严重烫伤大鼠早期创周和空肠组织血管的通透性,减轻组织水肿。

The influence of non-peptide NK1 receptor antagonist L-703,606 on the early tissue edema formation in rats with deep partial-thickness scald

OBJECTIVE: To investigate the influence of non-peptide neuro-kinase 1 (NK1) receptor antagonist L-703, 606 on the early tissue edema formation in rats with deep partial-thickness scald. METHODS: One hundred and fifty-two SD rats were enrolled in the study and were randomly divided into normal control (NC, n = 8), scald control (SC, n = 48, with 20% TBSA deep partial thickness scald), L-703, 606 treatment (LT, n = 48, with 20% TBSA deep partial-thickness scald 20 minutes after caudal vein injection of 250 nmol/kg L-703, 606) and beta-aescin treatment (AT, n = 48, with 20% TBSA deep-partial-thickness scald 30 minutes after caudal vein injection of 1.8 mg/kg beta-aescin) groups. The rats were sacrificed at 1, 4, 8, 24, 48 and 72 post scald hours (PSHs), with 8 rats at each time point. The peri-wound tissue and jejunum samples were harvested for the detection of vascular permeability and tissue water content with modified Evans blue extravasation method and average water content assay. RESULTS: The vascular permeability was significantly higher in the peri-wound tissue and jejunum in SC, LT an AT groups than that in NC group (P < 0.01) at 1 PSH, and it decreased gradually at 4 PSH. The vascular permeability in the peri-wound tissue in LT and AT group was significantly lower than that in SC group (P < 0.01), and that in LT group was markedly higher than that in AT group (P < 0.01) at 48 and 72 PSHs. The vascular permeability of jejunum tissue in LT group was lower than that in SC group within 24 PSH (P < 0.01), while that in AT group was lower than that in LT group at the early postscald stage (P < 0.01), but no obvious difference was found between the two groups after 72 PSH (P > 0.05). The change in the tissue water content was as follows: Dehydration was observed in peri-wound tissue in SC, LT and AT groups at 1 PSH. The tissue water content increased gradually thereafter and reached the peak at 8 and 24 PSH. Certain degree of dehydration was observed in jejunum tissue in SC, LT and AT groups at early postscald stage. The water content in jejunum tissue in LT group was evidently higher than that in SC and AT groups (P < 0.05 or 0.01), edema was evident at 8 PSH, and it became more obvious at 48 PSH, then it subsided gradually. Edema was less evident in LT group. CONCLUSION: Nonpeptide NK1-receptor antagonist L-703, 606 was able to mitigate the vascular permeability and reduce tissue water content in peri-wound and jejunal tissues.