苍耳子对内毒素免疫敏化大鼠的肝脏毒性

Hepatotoxicity Effect of Xanthii Fructus on Immune-sensitive Rat Model Induced by Endotoxin

目的:建立内毒素免疫敏化大鼠模型,观察苍耳子是否会诱发药物特异质肝损伤。方法:大鼠尾静脉注射0.7 mg·kg^-1脂多糖(LPS),于第1,7天共2次,建立内毒素免疫敏化模型。在模型基础上,苍耳子组分别每天灌胃苍耳子水提取物1.67,5.01,16.7 g·kg^-1,空白组和模型组每天灌胃等容积的蒸馏水,连续14 d,于灌胃后第7,14天两个流动时间点分别检测大鼠血清炎症因子白细胞介素-1β(IL-1β),白细胞介素-2(IL-2),白细胞介素-6(IL-6),白细胞介素-10(IL-10),肿瘤坏死因子-α(TNF-α);血清肝毒性生物标志物丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),总胆红素(TBil),碱性磷酸酶(ALP),总胆汁酸(TBA);苏木素-伊红(HE)染色观察肝脏病理学变化。结果:与空白组比较,内毒素免疫敏化模型表现为大鼠血清炎症因子IL-1β,IL-6水平明显升高(P<0.05,P<0.01);肝脏汇管区轻度炎细胞浸润(P<0.05);肝毒生物标志物ALT,AST,ALP,TBil,TBA变化差异无统计学意义。与模型组比较,苍耳子各剂量组大鼠的血清炎症因子、肝毒性生物标志物、肝脏病变程度差异无统计学意义。结论:苍耳子灌胃给药对内毒素免疫敏化模型大鼠的血清炎症因子、肝毒性生物标志物及肝脏病变程度均无明显影响,该结果提示苍耳子不会诱发药物特异质肝损伤。

Objective:To investigate the pharmaceutical idiosyncratic hepatotoxicity effect of Xanthii Fructus on the immune-sensitive rat model induced by endotoxin lipopolysaccharide(LPS).Method:The SD rats were randomly divided into five groups:control group,model group,and three Xanthii Fructucs groups.The immune-sensitive rat model was established by LPS(iv.0.7 mg·kg^-1,twice every 7 days).Then,the rats in control and model groups received the equal volume of distilled water,while the rats in Xanthii Fructus groups were administrated with water extract of Xanthii Fructus intragastrically(1.67,5.01,16.7 g·kg^-1,respectively)for 14 days.The serum and liver of the rats were collected on the 7 thand 14 thday to examine the levels of hepatotoxic biomarkers,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),alkaline phosphatase(ALP),and total bile acids(TBA),and liver histopathology.In addition,inflammatory factors,including interleukin-1β(IL-1β),interleukin-2(IL-2),interleukin-6(IL-6),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)of the idiosyncratic hepatotoxicity rats,were determined by enzyme-linked immunosorbent assay(ELISA).Result:The immunesensitive model rats showed elevated levels of IL-1β,IL-6(P<0.05,P<0.01),and mild inflammatory cells infiltrated in portal area of liver significantly(P<0.05),with no significant changes in hepatotoxic biomarkers.Meanwhile,there was no significant change between Xanthii Fructus groups and model rats in the levels of hepatotoxic biomarkers,inflammatory factors and hepatic lesions.Conclusion:Water extract of Xanthii Fructus intragastrically does not affect the levels of hepatotoxic biomarkers,inflammatory factors and hepatic lesions in rats induced by LPS intravenously.That is to say,Xanthii Fructus does not induce pharmaceutical idiosyncratic hepatotoxicity.