珍菊降压片中西药配伍减毒机制  

Detoxic attenuation mechanism of Zhenju Jiangya Tablets containing phyto-Chinese medicine extracts and chemical drugs' components

作　　者：谢家骏[1] 周广兴[2] 乔正东 成苗[4] 张国明[4] 王建新[5] 

机构地区：[1]上海中医药大学药物安全评价研究中心,上海201203 [2]复旦大学实验动物科学部,上海200032 [3]上海市浦东医院,上海201399 [4]上海市中药研究所,上海201401 [5]复旦大学药学院,上海201203

出　　处：《中成药》2015年第8期1633-1641,共9页Chinese Traditional Patent Medicine

基　　金：国家"十二五"科技重大专项课题(2011ZX09301-009);上海市科委中药现代化专项(04DZ19854)

摘　　要：目的探索珍菊降压片中西药配伍减毒机制,评价其长期给药的安全性。方法将Wistar大鼠随机分为珍菊降压片3 200、800、200 mg/kg剂量组、相应剂量的化药组分对照组以及空白对照组,每组30只,雌雄各半,连续给药26周,停药恢复期8周。结果化药组分对照组动物体重增长缓慢,血液红细胞数(RBC)、血红蛋白(HGB)、红细胞压积(HCT)、红细胞血红蛋白(MCH)、红细胞平均血红蛋白浓度(MCHC)先升高后降低,血清碱性磷酸酶(ALP)、游离氨基酸(NEFA)上升,总蛋白(TP)、白蛋白(ALB)、K+、Na+、Cl-下降,尿液Glu以及肝、肾、肾上腺、睾丸系数升高,部分动物肝细胞呈轻度脂肪变性,肾小管上皮细胞轻度颗粒样变性,停药后亦未见完全恢复。服用中西药配伍的珍菊降压片,200 mg/kg剂量组对化药组分所导致的异常能呈现完全的对抗,而3 200、800 mg/kg剂量组则呈现部分对抗。结论珍菊降压片中西药配伍用药具有完全或部分对抗源于化药组分所致的毒性作用,其程度与化药组分的剂量密切相关。珍菊降压片给大鼠连续26周灌胃的安全剂量为200 mg/kg,相当人临床剂量的18倍。AIM To investigate the safety and the detoxic mechanism of Zhenju Jiangya Tablets containing phyto-Chinese medicine and chemicals. METHODS The rats were treated with Zhenju Jiangya Tablets at a dose of 3 200,800,200 mg / kg respectively and its corresponding chemicals through intragastric administration once a day for 26 weeks. RESULTS After the administration of the chemical components,the animal body weight declined. RBC,HGB,HCT,MCH,MCHC initially increased and then decreased in the blood. ALP,NEFA,ALB,K^＋increased. TP,Na^＋,Cl^-decreased in the serum. Glu increased in the urine. The coefficients of liver,kidney,adrenal gland and testis increased. Some animal liver cells showed mild steatosis and some animal renal tubular epithelial cells showed mild granular degeneration. Both did not recover completely after the administration stopped. But Zhenju Jiangya Tablets could completely inhibit these adverse reactions at a dose of 200 mg / kg,and partly inhibit them at a dose of 3 200 and 800 mg / kg. CONCLUSION Zhenju Jiangya Tablets can completely or partially antagonize toxicity induced by the chemicals＇ components,and its antagonizing degree is closely related to the dosages of the chemicals＇ components. The safe dosage of Zhenju Jiangya Tablets by intragastric administration for 26 weeks on rats is 200 mg / kg,equivalent to 18 times of the clinical dosage for human.

关 键 词：珍菊降压片 盐酸可乐定 氢氯噻嗪 中西药配伍 长期毒性试验 减毒机制 安全剂量 

分 类 号：R259.441[医药卫生—中西医结合]