摘要
目的观察壮骨关节丸及所含药材对Beagle犬的肝脏毒性,寻找和确定壮骨关节丸引起肝损害的原因。方法按照故障排除法将壮骨关节丸全方拆分为最可能组(补骨脂组)、可能组(淫羊藿加独活组、乳香加没药组)、最不可能组(熟地组、续断加狗脊和鸡血藤组、骨碎补加桑寄生和木香组),与对照组和全方组进行Beagle犬的肝毒性对比研究,初步寻找出其中引起肝损害的药材组。将壮骨关节丸去掉毒性药材与全方进行肝毒性比较,对毒性药材进一步确认,每周称动物体重,从第3周开始监测血清生化指标。连续给药6个月,实验结束后取肝、脾、肾和肾上腺称重并计算脏器系数,对相应脏器进行病理检查。结果初筛发现乳香加没药组0.70g/kg犬血清中ALP、TC以及肝系数明显高于对照组,并且有1只犬肝脏汇管区有轻度胆管增生和胆汁淤积,熟地组犬血清TC水平升高,补骨脂组0.35g/kg犬血清ALP也高于正常对照组。壮骨关节丸全方组3.0g/kg从药后12周开始体重明显低于对照组,给药6周后ALP显著升高,3周后TC显著升高,肝、肾和肾上腺系数显著高于对照组,而去掉乳香和没药后的去乳香没药组2.65g/kg在6个月的实验中体重和ALP基本正常,仅13～20周高于对照组,且显著低于壮骨关节丸全方组,但TC依然显著升高。病理组织学检查表明全方组有3只犬肝脏内有轻度胆汁淤积,而对照组和去乳香没药组犬的肝脏均无胆汁淤积。结论壮骨关节丸中引起胆汁淤积的主要药材是乳香和没药,补骨脂对肝功能也有轻微影响。
Objective To observe hepatotoxicity of medicinal material in Zhuangguguanjie（ZGGJ） pill, to find and determine the hepatotoxic medicinal materials in ZGGJ pill. Methods ZGGJ formula was divided into the highest risk group（including Fructus Psoraleae）, higher risk groups（including Herba Epimedii＋Radix Angelicae Pubescentis and Ohbanum＋Myrrha） and lower risk groups（Radix Rehmanniae Preparata, Radix Dipsaci＋Rhizome Cibotii＋Caulis Spatholobi and Rhizoma Drynariae＋Herba Taxilli＋ Radix Aucklandiae） with hepatotoxicity risk of medicinal materials. A comparative study was made on hepatotoxicity of 6 medicinal material groups with control group and ZGGJ full formula group in Beagle, for finding the hepatotoxic medicinal materials. 18 Beagle dogs were divided control group, ZGGJ full formula group and non-full formula group which was removal Olibanum and Myrrha from ZGGJ formula. The dogs were administrated orally with ZGGJ full formula（3.0g/kg） and non-full formula（2.65g/kg） once a day for 6 months. The dogs were weighted once a week and serum biochemical indexes were determined from 3rd week after administration. In 26th week, the dogs were anesthetized and sacrificed after fasting for 16 hours, then liver, spleen, kidney, adrenal gland weights and coefficients were measured, and histopathologic examination was performed with lightmicroscope. Results The liver coefficient and serum ALP, TC of the dogs treated with Olibanum＋Myrrha were higher than those of control group, and one case had mild cholestasis and ductular proliferation in liver portal area. Serum TC of the dogs treated with Radix Rehmanniae Preparata was also higher than those of control group, and hepatic function of the dogs treated with Fructus Psoraleae was abnormal. Weights of the dogs treated with ZGGJ full formula were significiantly lower than those of control group from 12nd week after administration to the end of experiment, then ALP was significiantly higher from 6th week and TC from 3rd week. Coefficients of liver, kidney and adrenal gland were higher than control group. During the experiment, weight and ALP of dogs treated with non-full formula were only a few times higher than control group, but TC was still higher. Histopathologic examination showed that 3 cases of ZGGJ full formula group had mild cholestasis, but no cholestasis in liver of control group and non-full formula group. Conclusion Olibanum and Myrrha were the mainly hepatotoxic medicinal materials in ZGGJ pill, and yet Fructus Psoraleae had effects on hepatic function.
出处
《中国药物警戒》
2009年第11期641-648,共8页
Chinese Journal of Pharmacovigilance
关键词
壮骨关节丸
肝毒性
乳香
没药
补骨脂
熟地
Zhuangguguanjie pill
hepatotoxicity
Fructus Psoraleae
Olibanum
Myrrha
Radix Rehmanniae Preparata
