【摘要】 目的研究C25P肽对小鼠的急性毒性作用以及体外致癌性,为临床应用提供依据。方法采用最大耐受剂量法(MTD)进行对小鼠的急性毒性试验。对照组小鼠尾静脉注射生理盐水(40ml/kg);用药组小鼠尾静脉注射C25P多肽(3.64g/kg)。给药后连续观察14d。14d处死小鼠,测定血常规及血液生化学指标,并解剖小鼠进行病理组织学检查。并采用染色体畸变试验、细胞转化试验、非锚定依赖性生长试验对C25P多肽进行体外的致癌性评价。结果未出现小鼠死亡,用药组有3只小鼠发生轻微毒性反应;每组小鼠体质量均有增长,各组间的平均增长率无显著差异;所测血液生化指标中,用药组GPT(谷丙转氨酶)值比对照组呈显著性升高(P<0.05);用药组ALP(碱性磷酸酶)值比对照组呈显著性降低(P<0.05);大部分小鼠器官正常,发生毒性反应的3只小鼠的肺、脾、肝脏出现病变。C25P多肽的染色体畸变试验、细胞转化试验、非锚定依赖性生长试验均呈阴性。结论 C25P肽对受试动物无明显急性毒性作用以及无明显致癌性作用,属于低毒类药物。更多还原

【Abstract】 Objective To study the acute toxicity of C25P polypeptide, a CCR5 antagonist, in mice and its carcinogenic effect in vitro. Methods The acute toxicity of C25P polypeptide in mice was assessed by determinng the maximum tolerated dose (MTD). The mice were given C25P at the dose of 3.64 g/kg by tail vein injection, and the control mice received saline (40 ml/kg) injection. The mice were continuously observed for 14 days after the administration and sacrificed on day 14 for routine blood test, examination of the blood biochemistry and pathological examination. The carcinogenicity of C25P polypeptide in vitro was evaluated in cultured cell lines by chromosome aberration test, cell transformation test and non-anchorage dependent growth test. Results No mice died following administration of the drug, but 3 mice showed mild adverse reactions. The rats in both groups showed an increase in the body weight at a comparable rate. GPT increased and ALP decreased significantly in C25P polypeptide group (P<0.05). Most of the organs of the rats treated with in C25P polypeptide remained normal, but 3 mice showed pathologies in the lung, spleen and liver. Chromosome aberration test, cell transformation test and non-anchorage-dependent growth test all yielded negative results for C25P polypeptide. Conclusion C25P polypeptide is a low-toxicity drug that produces no apparent acute toxicity in mice or obvious carcinogenicity in vitro.更多还原