栀子水提物致大鼠肝脏毒性的时效与量效关系

Time-and dose-effect of Gardenia Jasminoides extract on hepatoxicity in rats

目的探讨栀子Gardenia jasminoides Ellis水提物对大鼠的肝脏毒性作用及其特征。方法给药组大鼠分为灌胃给予栀子水提物低、中、高(3、10、30 g/kg)剂量组,同时设灌胃给予去离子水空白对照组。给药期间每天观察,分别于给药7、14、28 d后采血,测定大鼠血清丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)、碱性磷酸酶(ALP)、谷氨酸脱氢酶(GLDH)活性以及总胆汁酸(TBA)和总胆红素(TBIL)的含有量;摘取肝脏称重并计算肝脏指数;常规切片,HE染色,光镜下观察肝脏组织病理学改变。结果给药7 d后,栀子水提物高剂量组大鼠开始出现摄食量减少,体质量增长缓慢,血清ALT、AST、ALP、TBA、TBIL、GLDH较空白对照组显著升高,中、高剂量组大鼠肝脏指数较空白对照组显著增大;给药14 d后,高剂量组大鼠血清ALP、TBA和TBIL较空白对照组显著升高,中、高剂量组大鼠肝脏指数较空白对照组显著增大;给药28 d后,高剂量组大鼠ALT和TBA、中剂量组TBIL和GLDH以及低剂量组GLDH较空白对照组显著升高,所有给药组大鼠肝脏指数均显著升高。病理组织学检查发现,给药7、14、28 d后,中、高剂量组大鼠均出现肝细胞肥大,小叶间胆管增生及炎症细胞浸润等不同程度病变。结论大鼠重复灌胃给予栀子水提物引起肝脏的毒性随剂量增加而增加,在高剂量时不随着时间增加而增加。

AIM To observe the relationship between dose effect and time effect on hepatoxicity of Gardenia jasminoides Ellis extract in rats. MOTItODS Wistar rats were divided into four groups： low, middle and high （3, 10, and 30 g/kg） dose of G. Jasminoides groups （administrated by gavage）, and the normal control group were orally given deionized water. All rats were observed daily during the administration period. On the 7th, 14th, 28th day after the administration, blood samples were collected; serum alanine transaminase （ALT） , aspartate transaminase （AST）, alkaline phosphatase （ALP）, glutamic dehydrogenase （GLDH） activity and total bile acid （TBA） and total bilirubin （TBIL） were determined. The livers were weighed and the liver index was calculated. HE staining and observation of histopathological changes in the structure of liver tissue under light microscopy were performed. RESULTS After the 7th day of administration, the rats in high dose group showed lower food consumption and slowly increased body weight. Serum ALT, AST, ALP, TBA, TBIL and GLDH in rats from high dose group were significantly higher than those in the normal control group. The liver index of rats in the middle and high dose groups was significantly increased than that in the normal control group. After the 14th day of administration, serum ALT, TBA and TBIL in rats from the high dose group were significantly higher than those in the normal group. The liver index of rats in the middle and high dose groups was significantly increased than that in the normal control group. After 28th day of administration, serum ALT and TBA in the rats from the high dose group, TBIL and GLDH in rats from the middle dose group, and GLDH in rats from the low dose group were significantly higher than those in the normal control group. The liver indexes of rats in all dose groups were significantly in- creased than those in the normal control group. After the 7th, 14th or 28th day of the treatment, histopathological changes such as the liver cell hypertrophy, interlobular bile duct hyperplasia, and inflammatory cell infiltration appeared in the middle and high dose groups. CONCLUSION The high dose of G. jasrninoides can induce and increase liver toxicity with the increase in dose, but at high dose level, liver toxicity does not increase with time.