抗菌肽R9对小鼠急性毒性及肾毒性的研究

Study on acute toxicity and nephrotoxicity of antimicrobial peptide R9 in mice

目的观察抗菌肽R9对小鼠的急性毒性和肾毒性。方法半数致死量(LD_(50))测定:给小鼠一次腹腔注射抗菌肽R9,观察7 d,按Bliss法计算LD_(50)及95%的可信限。R9肾毒性实验:小鼠随机分为4组,空白对照组(0.9%NaCl)和低、中、高3个剂量(抗菌肽R9:6.7,10.0,15.0 mg·kg^(-1))实验组,分别一次腹腔注射。于给药第2天,测定血液学指标;检测肌酸酐、尿素氮、总蛋白;计算肾系数。结果R9的LD_(50)为21.3 mg·kg^(-1),95%可信限为19.1~23.5mg·kg^(-1)。给药第2天,与空白对照组比较,高剂量实验组小鼠的白细胞(4.07×10~9/L)和红细胞(8.96×10^(12)/L)明显减少而肌酸酐(19.99μmol·L^(-1))和尿素氮(8.07 mmol·L^(-1))升高,差异均有统计学意义(P<0.05,P<0.01);同时,总蛋白(54.18 g·L^(-1))降低而肾系数(13.40 mg·g^(-1))升高,差异均有统计学意义(均P<0.05)。结论抗菌肽R9对小鼠有一定毒性,肾是主要毒性靶器官。肾毒性与给药剂量呈正相关,停药后有可逆性好转趋势。

Objective To observe the acute toxicity and nephrotoxicity of antibacterial peptide R9 in mice. Methods Median lethal dose(LD（50）） test： Antimicrobial peptide R9 was intraperitoneally injected into mice. After 7 d of observation,the LD（50） and 95% confidence limits were calculated according to the Bliss method. Renal toxicity of R9 test： 80 mice were randomly divided into 4 groups： the low,medium and high dose(6. 7,10,15 mg·kg-1 R9） experimental groups and blank control group(distilled water） were injected intraperitoneally. The blood samples were collected on the 2 nd day respectively from 10 mice,then blood indexes were tested. The serum were separated,then creatinine,blood urea nitrogen and total protein were measured. Kidneys and other organs were taken to calculate the organ coefficients. Results The LD（50） of antimicrobial peptide R9 was 21. 3 mg·kg-1,and its 95% confidence limit was 19. 1-23. 5 mg · kg-1. On the second day after administration,WBC(4. 07 × 109/L） and RBC(8. 96 × 1012/L） in the high dose experimental group decreased compared with the blank control group,the differences were statistically significant difference(P〈0. 01,P〈0. 05）.Creatinine(19. 99 μmol·L-1） and urea nitrogen(8. 07 mmol·L-1）increased with significant(P〈0. 05,P〈0. 01）. The total protein(54. 18 g·L-1） decreased with significant(P〈0. 05） and the kidney coefficient(13. 40 mg · g-1） increased with significant(P〈0. 05）.Conclusion A single intraperitoneal injection of antimicrobial peptide R9 can produce certain toxicity to mice,and the kidney was the main target organ. Nephrotoxicity was positively correlated with dose,and there was a trend of reversible improvement after withdrawal.