千金子制霜前后提取物对正常及癌性腹水模型小鼠泻下逐水效应与毒性研究

Water-expelling Effects and Toxicity of Euphorbiae Semen before and after Powdering in Normal and Cancerous Ascites Model Mice

目的:筛选千金子泻下逐水药效部位,探究其制霜前后泻下逐水效应及结肠、肾脏毒性的变化。方法:采用H22癌性腹水模型小鼠,以腹水量、粪便含水量、尿量等生物效应指标筛选千金子药效部位;采用H22癌性腹水模型小鼠,灌胃千金子生品、霜品石油醚部位,结合生物效应指标、脏器指数、肾脏功能指标、氧化应激指标、炎症因子含量及水通道蛋白表达考察千金子的泻下逐水效应;采用正常小鼠,以脏器指数、肾脏功能指标、氧化应激指标、炎症因子含量考察千金子制霜前后的毒性差异。结果:千金子制霜前后石油醚部位能够提高癌性腹水模型小鼠粪便含水量、尿量,降低小鼠腹水量(P<0.05,P<0.01),非石油醚部位无显著作用。药效实验结果显示,与模型组比较,各给药组小鼠组织损伤显著减轻,在灌胃石油醚部位后小鼠血清尿素氮(BUN)、肌酐(Cr)含量降低,总超氧化物歧化酶(SOD)含量升高,丙二醛(MDA)含量下降,结肠、肾脏组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的含量显著降低,且能抑制结肠、肾脏组织中水通道蛋白1(AQP1)和水通道蛋白3(AQP3)蛋白表达水平。毒性结果显示,与对照组比较,各正常给药组小鼠给药后可见不同程度的结肠、肾脏组织损伤,TNF-α、IL-1β分泌增加,肾功能指标呈上升趋势,SOD含量显著降低,MDA含量显著升高,制霜后该损伤降低。结论:石油醚部位是千金子制霜前后泻下逐水的药效部位,千金子制霜后毒性显著降低的同时,其泻下逐水功效得以保留,表现为减毒存效。

Objective:To screen the effective fractions of Euphorbiae Semen(ES)and Euphorbiae Semen Pulveratum(ESP)for expelling water and investigate the changes of the water-expelling effect and colonic and renal toxicity before and after powdering.Methods:The mouse model of H22 hepatocellular carcinoma with cancerous ascites was used to screen the effective fraction with ascites fluid volume,fecal water content,and urine volume as indicators.The modeled mice were administrated with the petroleum ether fractions of ES and ESP by gavage,and the water-expelling effects of ES and ESP were evaluated based on the biological effect indicators,organ indices,liver and kidney function indicators,oxidative stress markers,inflammatory mediator levels,and expression of aquaporins(AQPs).Normal mice were used to examine the differences in toxicity of ES before and after powdering based on organ indices,liver and kidney function indicators,oxidative stress markers,and inflammatory mediator levels.Results:The petroleum ether fractions of ES and ESP increased the fecal water content and urine volume and reduced the ascites fluid volume of the modeled mice(P<0.05,P<0.01),while the non-petroleum ether fraction had no obvious effect.Compared with the model group,the administration with the petroleum ether fractions of ES and ESP alleviated the tissue damage,lowered the serum levels of blood urea nitrogen(BUN)and creatine(Cr),increased the superoxide dismutase(SOD)content,reduced the malondialdehyde(MDA)content,inhibited tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)secretion in the colonic and renal tissue,and down-regulated the protein levels of AQP1 and AQP3 in the colonic and renal tissue.Compared with the blank group,the administration of ES caused different degrees of damage in the colonic and renal tissue,increased secretion of TNF-αand IL-1βand renal function indicators,and significantly lowered the SOD level and elevated the MDA level,which were alleviated in the group administrated with ESP.Conclusion:The petroleum ether fraction is the effective fraction of ES and ESP for expelling water.Powdering attenuated the toxicity while retaining the water-expelling effect of ES.