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目的观察重复灌胃给予SD大鼠SCZKG所产生的毒性反应及其严重程度。方法 SD大鼠随机分为7.7,15.4和28.0 g·kg-1组和溶媒对照组,连续灌胃给药4周、停药恢复性观察2周。结果①给药期间,中剂量组和高剂量组有部分动物出现稀便和(或)水样便和(或)肛门周围不清洁、此两组动物摄食量减少和饮水量增加(有剂量-反应关系),三个剂量组雄鼠体重增长较溶媒对照组略缓慢(高剂量组较明显),各组间比较有显著性差异(P<0.05),停药后粪便性状及排泄正常,各组动物摄食及饮水量相当、雄鼠体重有所恢复;②给药4周给药组动物血清的EOS%,RBC,MCV,Retic%,PT,TG,CHOL,GLU,BUN,K+,Na+和Ca,组间比较有显著性差异(P<0.05),虽EOS%,Retic%,GLU,K+和Na+有剂量-反应趋势,但无时间-反应关系,除Retic%和BUN外,其余指标均在本中心正常历史背景资料范围内小幅波动,故无生物学意义;③给药4周给药组雌鼠肝、左肾、右肾、肾脏重量及系数和各脏脑比值,脾脏系数和脾/脑比值,给药组雄鼠肝、右肾、肾的系数,低、高剂量组肝/脑比值、脾重量、胸腺重量及系数和胸腺/脑比值,组间比较均有显著性差异(P<0.05),除雌鼠右肾重量、脾系数、肝/脑和脾/脑比值,雄鼠右肾、肾、胸腺系数和肝/脑比值外均有剂量-反应关系;④组织病理学镜检,可见肝病变仅在溶媒对照组发生、睾丸及附睾病变仅见于恢复期高剂量组单例、肾脏和前列腺病变在溶媒对照组及高剂量组均有发生,但两组病变发生率和病变程度组间比较均无显著性差异(P>0.05),故推测上述病变可能与动物自发病变有一定相关性。结论 SCZKG 7.7 g·kg-1(临床人拟用剂量的13.8倍)以下为无毒性反应剂量,临床需重点关注胃肠道反应,以及食欲、饮水、体重、肝、肾、脾功能的变化情况。
Objective To observe the toxicity and severity of SCZKG induced by repeated intragastric administration in SD rats. Methods SD rats were randomly divided into 7.7, 15.4 and 28.0 g · kg -1 groups and vehicle control group. The rats were orally administrated for 4 weeks. The recovery was observed for 2 weeks. Results ① During the administration period, some animals in the medium dose group and high dose group had loose stools and / or watery stools and / or unclean surroundings, and their food intake and water intake increased (dose- (P <0.05). The stool performance and excretion of each group were normal after stopping the treatment (P <0.05). The body weight of the three dose groups was slightly slower than that of the vehicle control group (the high dose group was more obvious) The rats fed with the same diet had the same amount of drinking and drinking water, and the body weight of the male rats recovered. The serum EOS%, RBC, MCV, Retic%, PT, TG, CHOL, GLU, BUN, K +, Na + (P <0.05). There was no dose-response relationship between EOS%, Retic%, GLU, K + and Na + except for Retic% and BUN There is no biological significance in the range of the normal historical background of the center; ③The weights and coefficients of liver, left kidney, right kidney, kidney, and the ratios of various organs of the mice in the 4-week administration group, the spleen coefficient and spleen / Brain ratio, the coefficient of liver, right kidney and kidney, the liver / brain ratio of low and high dose groups, spleen weight, thymus weight and coefficient and thymus / (P <0.05). Except for the right kidney weight, spleen coefficient, liver / brain and spleen / brain ratio, the right kidney, kidney, thymus index and liver / Response relationship; ④ histopathological microscopy, visible liver lesions occurred only in the vehicle control group, testicular and epididymal lesions only found in recovery high-dose single case, renal and prostate lesions in the vehicle control group and high-dose group have occurred, However, there was no significant difference between the two groups in the incidence of lesions and the degree of lesion (P> 0.05). Therefore, it is speculated that the above lesions may be related to the spontaneous lesion in animals. Conclusions SCZKG 7.7 g · kg-1 (13.8 times of clinical dose) is the non-toxic reaction dose, the clinical need to focus on gastrointestinal reactions, as well as appetite, drinking water, body weight, liver, kidney and spleen function changes .