目的 研究補骨脂水提藥渣大鼠ig給藥的長期毒性。方法 SD大鼠70只，按體質量、性別隨機分為5組：對照組、補骨脂生藥粉高、低劑量組，補骨脂水提藥渣高、低劑量組（各組高、低劑量均相當于生藥6、3 g/kg，分別為臨床等效劑量的11.11、5.56倍），每組14只，雌雄各半，每日ig給藥1次，連續(xù)給藥12周。每周稱大鼠體質量，藥結束后，取心臟、肝臟、脾臟、腎臟、胸腺，稱質量并計算臟器系數；血細胞分析儀檢測血液學指標；全自動生化儀血清生化學指標；試劑盒法檢測大鼠肝臟中氧化應激指標；做肝臟和腎臟組織病理學檢查。結果 與對照組比較，生藥粉和藥渣高劑量組雄性大鼠體質量均顯著下降（P<0.05），而藥渣組雌性大鼠體質量隨給藥時間延長無顯著性變化；補骨脂生藥粉和水提藥渣雌性、雄性大鼠的肝系數均顯著升高（P<0.01）；雄性大鼠生藥粉和藥渣高劑量組、雌性大鼠生藥粉組和藥渣高劑量組腎系數顯著升高（P<0.05、0.01、0.001）；雄性大鼠生藥粉高劑量組血小板（PLT）水平，藥渣低劑量組紅細胞（RBC）水平顯著升高，生藥粉低劑量組和藥渣低劑量組白細胞（WBC）水平，藥渣高劑量組PLT水平顯著下降，雌性大鼠各給藥組PLT均顯著下降（P<0.05）；雄性大鼠生藥粉組堿性磷酸酶（ALP）和三酰甘油（TG）水平均顯著下降，總蛋白（TP）水平顯著升高，生藥粉低劑量組尿素氨（BUN）水平顯著下降（P<0.05、0.01、0.001）；藥渣高劑量組TP和白蛋白（ALB）、藥渣低劑量組天冬氨酸轉氨酶（AST）顯著升高，丙氨酸轉氨酶（ALT）和ALP顯著下降（P<0.05、0.01、0.001）；雄性大鼠生藥粉高劑量組和藥渣組丙二醛（MDA）顯著升高（P<0.05），雌性大鼠生藥粉組MDA和總抗氧化能力（T-AOC）、藥渣組MDA均顯著下降（P<0.05、0.01）。結論 長時間給予大劑量補骨脂水提藥渣，對大鼠肝臟和腎臟功能均造成一定損害。

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.

R965.3

國家自然科學基金（81673826、81703790）；國家重大新藥創(chuàng)制專項（2014ZX09304307-001-005）