补骨脂水提药渣大鼠三个月长期毒性试验研究

Study of three months long-term toxicity of rats with water extracts residue of Psoralea corylifolia

目的研究补骨脂水提药渣大鼠ig给药的长期毒性。方法 SD大鼠70只,按体质量、性别随机分为5组:对照组、补骨脂生药粉高、低剂量组,补骨脂水提药渣高、低剂量组(各组高、低剂量均相当于生药6、3 g/kg,分别为临床等效剂量的11.11、5.56倍),每组14只,雌雄各半,每日ig给药1次,连续给药12周。每周称大鼠体质量,药结束后,取心脏、肝脏、脾脏、肾脏、胸腺,称质量并计算脏器系数;血细胞分析仪检测血液学指标;全自动生化仪血清生化学指标;试剂盒法检测大鼠肝脏中氧化应激指标;做肝脏和肾脏组织病理学检查。结果与对照组比较,生药粉和药渣高剂量组雄性大鼠体质量均显著下降(P<0.05),而药渣组雌性大鼠体质量随给药时间延长无显著性变化;补骨脂生药粉和水提药渣雌性、雄性大鼠的肝系数均显著升高(P<0.01);雄性大鼠生药粉和药渣高剂量组、雌性大鼠生药粉组和药渣高剂量组肾系数显著升高(P<0.05、0.01、0.001);雄性大鼠生药粉高剂量组血小板(PLT)水平,药渣低剂量组红细胞(RBC)水平显著升高,生药粉低剂量组和药渣低剂量组白细胞(WBC)水平,药渣高剂量组PLT水平显著下降,雌性大鼠各给药组PLT均显著下降(P<0.05);雄性大鼠生药粉组碱性磷酸酶(ALP)和三酰甘油(TG)水平均显著下降,总蛋白(TP)水平显著升高,生药粉低剂量组尿素氨(BUN)水平显著下降(P<0.05、0.01、0.001);药渣高剂量组TP和白蛋白(ALB)、药渣低剂量组天冬氨酸转氨酶(AST)显著升高,丙氨酸转氨酶(ALT)和ALP显著下降(P<0.05、0.01、0.001);雄性大鼠生药粉高剂量组和药渣组丙二醛(MDA)显著升高(P<0.05),雌性大鼠生药粉组MDA和总抗氧化能力(T-AOC)、药渣组MDA均显著下降(P<0.05、0.01)。结论长时间给予大剂量补骨脂水提药渣,对大鼠肝脏和肾脏功能均造成一定损害。

Objective To study the long-term toxicity of ig administration of Psoralea corylifolia aqueous extracts residue in rats.Methods Tatolly 70 SD rats were randomly divided into five groups according to body weight and sex: control group, high and low dose group of P. corylifolia powder, high and low dose group of P. corylifolia water extract residue(high and low doses were equivalent to 6 and 3 g/kg of crude drugs, 11.11 and 5.56 times of clinical equivalent doses respectively). Fourteen rats in each group were ig given drugs once a day for 12 weeks. The weight of rats was weighed every week. After the treatment, the heart, liver,spleen, kidney and thymus were taken to weigh and calculate the organ coefficient. The hematological indexes were detected by blood cell analyzer;The serum biochemical indexes were detected by automatic biochemical analyzer;The oxidative stress indexes in the liver of rats were detected by kit method;And the liver and kidney were examined by histopathology. Results Compared with the control group, the body weight of male rats in the high dose group and the high dose group of drug residue were decreased significantly(P < 0.05), while the body weight of female rats in the drug residue group did not change significantly with the administration time. The liver coefficients of female and male rats with lipid and water extracts were significantly increased(P <0.01);PLT in high dose P. corylifolia powder group of male rats and RBC in low dose group of drug residue were significantly increased. In the low-dose group of WBC, the PLT of the high-dose dregs group was decreased significantly, and the PLT of the female rats in each dose group was decreased significantly(P < 0.05). The ALP, TG and BUN of the male rats in the crude drug group were decreased significantly, and the TP was increased significantly. TP and ALB were significantly increased in the high dose group of drug residue(P < 0.05 and 0.01). MDA in the crude drug group and the dregs group of female rats were significantly decreased(P < 0.05, 0.01 and 0.001). Conclusion Long-term administration of Psoralea corylifolia aqueous extracts residue has caused certain damage to liver and kidney function in rats.