目的 研究SD大鼠連續(xù)iv冠心寧注射液13周的毒性反應(yīng)。方法 120只大鼠隨機(jī)分為4組：溶媒對照組和冠心寧注射液高、中、低劑量（3.40、1.70、0.85 g/kg）組，雌雄各半。連續(xù)iv給藥13周，每周檢測1次體質(zhì)量和攝食量，每天觀察動物藥后外觀體征變化，分別于給藥結(jié)束和停藥4周時進(jìn)行臟器相對質(zhì)量（臟腦比）、血液學(xué)指標(biāo)、血液生化學(xué)指標(biāo)、組織病理學(xué)檢查。結(jié)果 冠心寧注射液3.40、1.70 g/kg每次藥后即刻出現(xiàn)呼吸急促、步態(tài)不穩(wěn)、俯臥不動、眼球突出等征狀，隨給藥時間的延長，上述癥狀逐漸減輕，恢復(fù)時間逐漸縮短；0.85 g/kg劑量組動物未出現(xiàn)明顯的異常反應(yīng)。冠心寧注射液3.40 g/kg劑量下2只雄性動物給藥約4周時死亡，0.85、1.70 g/kg劑量組均未出現(xiàn)動物死亡。與溶媒對照組比較，0.85、1.70 g/kg劑量組動物血液學(xué)、血液生化學(xué)、臟器相對質(zhì)量、組織病理學(xué)檢查均未見明顯異常；冠心寧注射液3.40 g/kg劑量下給藥13周后可導(dǎo)致大鼠血液中尿素氮（BUN）水平明顯升高、腎臟相對質(zhì)量明顯增加；停藥4周后，上述各項指標(biāo)均恢復(fù)正常，其余檢測指標(biāo)未見明顯異常。結(jié)論 重復(fù)大劑量iv冠心寧注射液對大鼠有腎臟毒性，重復(fù)iv給予0.85 g/kg無毒性反應(yīng)，是臨床等效劑量的12倍。

Objective To observe the repeat administration toxicity of Guanxinning Injection in rats.Methods Totally 120 rats (males and females) were randomly divided into vehicle control group and three Guanxinning Injection groups with different dosages (3.40, 1.70, and 0.85 g/kg). Rats were administered with Guanxinning Injection by consecutive intravenous injection for 13 weeks. Besides the general conditions were observed, the related indexes were detected, such as body weight, the routine control of blood, hepatic function, renal function, the metabolism condition of lipids, the glycometabolism indexes, and histopathology analysis were determined at 13 weeks of treatments and 4 weeks after the withdrawal, respectively.Results Rats in the Guanxinning Injection group at 3.40, 1.70 g/kg apperance shortness of breath, unsteady gait, lying motionless, and other symptoms. There was no obvious abnormal reaction in the 0.85 g/kg dose group. There were two male rats in the Guanxinning Injection group at 3.40 g/kg died at about week 4 of treatments, and there was no death in the 0.85 and 1.70 g/kg dose groups. Compared with vehicle control group, the related indexes of blood, blood biochemistry, organ relative quality, and histopathological showed no obvious abnormalities in Guanxinning Injection 0.85 and 1.70 g/kg group. The levels of urea nitrogen (BUN) and the relative weight of kidney in Guanxinning Injection 3.40 g/kg group were significantly higher than those in vehicle control group at 13 weeks. The change of these parameters regained to normal at 4 weeks after withdrawal and the rest of the detection index showed no obvious abnormality in 3.40 g/kg dase group.Conclusion Intravenous administration of Guanxinning Injection for 13 weeks at high dose could induce reversible damage to kidney.