柴胡总皂苷醇洗脱精制品对大鼠慢性肝毒性“量-毒”关系研究

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目的:观察连续15 d给予大鼠不同剂量的柴胡总皂苷醇洗脱精制样品导致大鼠肝毒性的损伤程度。方法:分别给予大鼠灌胃高、中、低剂量的柴胡总皂苷醇洗脱精制样品,按柴胡总皂苷计算,高、中、低剂量组分别为300,150,50 mg.kg-1,除观察一般状况外,检测血中肝功、肾功、脂质代谢、糖代谢相关指标;剖杀大鼠,精密称量心、肝、脾、肺、肾脏质量,计算脏体比值;进行肝脏病理组织学检查。结果:不同剂量的柴胡总皂苷醇洗脱精制样品可导致大鼠体重下降,导致血中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)、白蛋白(ALB)和总胆红素(TBI)水平增高,肝脏质量和肝体比值增大,病理学检查可见不同程度的肝组织损伤;上述变化随剂量的增加而逐渐加重,与空白组比较有明显差异。对尿素氮(BUN)、肌酐(Cr)、总蛋白(TPC)、胆固醇(CHO)、血糖(GLU)含量影响不明显。结论:柴胡对大鼠肝毒性损伤程度与柴胡用药剂量、柴胡总皂苷含量呈剂量依赖关系,并呈现一定的“量-毒”关系。柴胡总皂苷是柴胡导致肝毒性的毒效部位,柴胡总皂苷醇洗脱精制品(81.9%)在一定剂量下,连续给药15 d即可导致大鼠明显的肝脏器质性病变,其细胞损伤乃至坏死是主要病理改变。 OBJECTIVE: To observe the degree of damage of rat hepatotoxicity caused by elution of refined samples of Bupleurum total saponin at different doses on rats for 15 days. Methods: The rats were given high, medium and low doses of emodin total saponin elution refined samples, according to the total saikosaponin, high, medium and low dose groups were 300,150,50 mg.kg-1, In addition to observing the general situation, the liver function, renal function, lipid metabolism, glucose metabolism related indicators were measured; the rats were killed, the heart, liver, spleen, lung and kidney weights were accurately weighed to calculate the ratio of the soils; Histopathological examination. Results: Elution of refined samples with different dosages of total saponins from Bupleurum ophthalmus resulted in the decrease of body weight in rats, leading to the changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase AKP, ALB and TBI increased, liver mass and ratio of liver increased, pathological examination showed different degrees of liver damage. The above changes gradually increased with the increase of dose, There were significant differences in the blank group. The effects of BUN, Cr, TPC, CHO and GLU were not obvious. CONCLUSION: Bupleurum has a dose-dependent relationship with the dose of Bupleurum chinense and the dose of Bupleurum chinense and the degree of hepatotoxicity in rats. Bupleurum total saponin is the toxic effect of Bupleurum leading to hepatotoxicity. Bupleurum total saponin eluting product (81.9%) under certain dose, continuous administration of 15 d can lead to obvious liver organic disease in rats , Its cell damage and necrosis are the main pathological changes.
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