【摘要】 目的:对含剧毒药马钱子的热痹清片进行长期毒理学研究,观察大鼠连续重复给予热痹清片后,机体产生的毒性反应及其严重程度,主要的毒性靶器官及其损害的可逆性,提供无毒性反应剂量及临床上主要的监测指标,为制定人用剂量提供参考,以确保临床用药的安全性。方法:以120只SD大鼠为受试对象,每组30只,雌雄各半,随机分为正常对照组、热痹清片高剂量组6.9g(生药)·kg-1、中剂量组3.45g(生药)·kg-1和低剂量组1.73g(生药)·kg-1,分别相当于人拟临床用药量的10倍、5倍和2.5倍。采用灌胃给药途径给药,正常对照组给予等容积纯净水,连续给药6个月,观察大鼠有无死亡及其毒性反应。在给药3个月、6个月后及停药后3周内(恢复期)各组分别处死10只大鼠,取血及脏器组织并检测生长发育、血液学、血液生化学、组织病理等指标的变化。结果:连续给药6个月,正常组和各给药组大鼠精神状态良好,行为活动、呼吸正常,未见有腺体异常分泌,皮毛光滑,粪便和尿液未见异常,体重增长正常,停药后3周内也未见异常情况发生。在给药中期(3个月)及给药结束时(6个月),动物体重增长值与空白对照组比较差异不显著(P>0.05),给药3个月、6个月及恢复期内,各组大鼠血液学指标及血液生化学指标均在正常范围内,未见药物对大鼠血液学指标有明显影响。血液学和血液生化学指标检查结果给药组与空白对照组比较差异不显著(P>0.05),给药3个月、6个月及恢复期内各组大鼠脏器指数均在正常范围内,未见药物对大鼠脏器指数有明显影响。给药3个月、6个月和恢复期内,正常组与高剂量组动物脏器组织病理组织学检查结果表明,该药对大鼠的各重要脏器均未出现与药物相关的病理学改变。结论:长期毒性研究表明,热痹清片在规定剂量下服用是安全的。更多还原

【Abstract】 Objective: To make a long-term study on Rebiqing tablet containing virulent nuxvomica. After successively feeding Rebiqing tablet to rats, we observed the toxic reaction and its degree, main target organ and its reversibility of damage, providing a virulent reaction dosage and main detection index for the safe dosage for patients. Methods: 120 SD rats were randomly divided into 4 groups with same male and female: normal-controlled group, Rebiqing high-dose group [ 6.9g(raw)·kg-1 ], middle-dose group [ 3.45g(raw)·kg-1 ] and low-dose group [ 1.73g(raw)·kg-1 ], corresponding 10, 5 and 2.5 times of human dosage. We gave them intragastric administration for 6 months, but the normal group pure water only, and observed the results of death and toxic reaction. After administration for 3, 6 months or stopping drugs after 3 weeks (convalescence), 10 rats were found dead. Took blood sample and organ tissue to examine index changes on growth, hematology, blood biochemistry and histopathology. Results: After giving rats drugs for 3, 6 months, the normal group and groups taking drugs were all in good spirit, with normal behavior and respiration, no abnormal gland secretion and normal body weight, even 3 weeks after stopping drugs. In the mid-term (3 months) or end (6 months) of the administration, the increase of body weight had no obvious difference from the controlled group (p>0.05). After 3-month, 6-month administrationhematologic and blood biochemical index of each group were normal, with no obvious effects on the hematologic index of the rats.The difference of hematologic and blood biochemical index between the administration team and the controlled group was not obvious ( P > 0.05 ) . After 3-month, 6-month administration or during the convalescent period, organic index of each group were norm, with no obvious effects on the organic index. After 3-month, 6-month administration or during the convalescent period, histopathologic examination of normal group and high-dose group showed that organs of rats had no obvious drug-related pathological changes. Conclusion: Long-term study of toxicity showed that rebiqing was safe taken under formulary dosage.更多还原