C5a反义肽对脓毒症小鼠的保护作用及其机制

Protective effects of antisense peptide of C5a in experimental sepsis

目的研究C5a反义肽R4在小鼠体内拮抗C5a的活性以及它对小鼠CLP后脓毒症的保护作用。方法小鼠CLP后分为实验组和对照组,实验组小鼠CLP后立即尾静脉注射反义肽 R4,剂量分别按1．0、2．0、4．0、8．0mg／kg体重,观察小鼠的生存率。取实验组小鼠(4 mg／kg体重) 取血液和肺组织,检测血清ALT、AST、BUN、肌酸酐、尿酸和肺的髓过氧化物酶(MPO)浓度。结果 (1)对照组小鼠ALT、AST、BUN、肌酸酐、尿酸、肺的MPO浓度分别为(344．416±29．786)、 (375．350±13．373)U／L,(25．233±6．006)mmol／L、(48．933±7．306)、(456．000±152．526)μmol／ ml、(4．476±0．880)U／g。正常小鼠组以上参数分别依次为(24．520±8．097)、(116．983±40．963) U／L、(6．917±1．585)mmol／L、(11．083±1．833)μmol／ml、(52．800±9．200)μmol／ml,(0．456± 0．081)U／g。实验组以上参数分别依次为(60．933±7．960)、(163．433±7．925)U／L,(7．200± 1．311)mmol／L,(18．600±1．708)μmol／ml,(158．166±6．924)μmol／ml,(1．005±0．107)U／g。对照组较实验组和正常组小鼠损伤明显,实验组小鼠以上参数较对照组的发生有意义的改善(P< 0．05)。(2)实验组小鼠生存率(33％～50％)比对照组小鼠明显提高(P<0．05)。结论该结果显示 C5a反义肽在小鼠体内有着良好的拮抗C5a的作用,揭示了治疗脓毒症的一种新的药物治疗范畴。

Objective To evaluate the antisense peptide of C5a in the sepsis model of cecal ligation and puncture （CLP） for their protective effects in mouse. Methods Mice were subjected to cecal ligation and puncture （CLP）. Drug-treated mice received antisense peptide of C5a （1,2, 4 and 8 mg/kg, i, v） through the tail vein after CLP and the survival rate was observed. Levels of circulating alanine and aspartate aminotransferase （ALT/AST）, creatinine, blood urea nitrogen （BUN）, uric acid and myeloperoxidase （MPO） concentrations in the lung of the drug-treated mice receiving antisense peptide of C5a （4 mg/kg） were determined. Results Sepsis was characterized by significant elevations of ALT, AST, creatinine, BUN, acidum uricum, organ MPO concentrations. In untreated group these parameters were （344.416± 29.786）, （375.35± 13.373） U/L, （25.233± 6.006） mmol/L, （48.933± 7.306）, （456.000 ± 152.526） μmol/ml and （4. 476 ± 0. 880） U/g respectively, in normal group, they were （24.520± 8.097）, （116.983± 40.963） U/L, （6.917± 1.585） mmol/L, （11.083± 1.833）, （52. 800 ± 9. 200） μmol/ml and 0. 456± 0. 081 × 10^-2 U/g respectively, and in treated group they were （60.933± 7.960）, （163.433± 7.925） U/L, （7.200± 1.311） mmol/L, （18.600± 1.708） μmol/ml and （158. 166± 6. 924） μmol/ml respectively. The survival rate in untreated group treated group was 0 and 33%-50% （2-3/6） respectively （P〈 0.05）. Conclusion These data suggest that the antisense peptide of C5a has an antagonistic effect against C5a in vlvo and suggest a possible new drug therapeutic category for treating sepsis.