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目的:研究柴胡总皂苷对大鼠肝脏线粒体功能、与能量损伤相关肝功和病理指标的影响,探讨其致大鼠肝毒性损伤的能量机制。方法:连续15 d给大鼠灌胃高、中、低不同剂量的柴胡总皂苷醇洗脱物,按柴胡总皂苷计算剂量分别为300,150,50 mg.kg-1。检测血清部分肝功指标;测定肝脏线粒体呼吸功能,ATP含量及ATP酶活性的变化;计算心、肝、脾、肺、肾脏/体比值和肝病理组织学检查。结果:柴胡总皂苷各剂量组大鼠肝脏线粒体呼吸控制率(PCR)、磷氧比值(P/O)、呼吸耗氧量、ATP含量和ATP酶活性均明显降低;血中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和白蛋白(ALB)水平升高;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。结论:柴胡总皂苷在一定剂量下可通过抑制线粒体呼吸功能、影响肝脏能量代谢造成肝脏毒性损伤,是否还有其他肝毒性机制有待进一步探讨。
OBJECTIVE: To study the effects of saikosaponins (SSP) on the hepatic mitochondrial function and liver function and pathological parameters related to energy damage in rats, and to explore the energy mechanism of Bupleurum total saponins on liver injury in rats. Methods: Rats were administered with high, medium and low dose of Bupleurum total saponin eluate on the 15th day. The dosages of total saponins of Bupleurum chinense were 300,150 and 50 mg.kg-1, respectively. The serum level of liver function index was measured. The change of mitochondrial respiratory function, ATP content and ATPase activity were measured. The heart, liver, spleen, lung, kidney / body ratio and liver histopathological examination were calculated. Results: The liver mitochondrial respiratory control rate (PCR), P / O ratio, respiratory oxygen demand, ATP content and ATPase activity were significantly decreased in all doses of Bupleurum total saponins. The levels of alanine amino (ALT), aspartate aminotransferase (AST) and albumin (ALB) levels increased; liver mass and liver ratio increased; pathological examination showed varying degrees of liver tissue damage. The above changes gradually increased with the increase of dose, compared with the blank group there are significant differences. Conclusion: Bupleurum saponin can inhibit the respiratory function of mitochondria at certain dose and affect the hepatic toxicity induced by energy metabolism of the liver. Whether there are other mechanisms of hepatotoxicity remains to be further explored.