蟾酥微丸的急性与亚慢性毒性研究

试验旨在观察蟾酥微丸对小鼠急性毒性和大鼠长期毒性作用，评价其安全性，为临床用药提供理论依据。急性毒性试验选取昆明小鼠，2次灌服蟾酥微丸，测定蟾酥微丸的急性毒性。亚慢性毒性试验选取120只SD大鼠，平均分为低、中、高蟾酥微丸药物组和空白组（给予等体积的蒸馏水），灌胃给药，分别在连续给药28 d后和停药2周后称重，随机选取每组20只大鼠（停药后余下10只）心脏采血处死，检测血液学、血液生化指标并做病理组织学检查。急性毒性试验用药死亡时间集中在1~4 h，经计算LD₅₀为13.21 g/kg。亚慢性毒性试验中，连续给药28 d后，高、中剂量组雄性大鼠的体重与空白组差异极显著（P＜0.01）；高剂量组的谷草转氨酶与碱性磷酸酶与空白组相比差异极显著（P＜0.01）；高、中剂量组的肾脏系数与空白组相比差异极显著（P＜0.01）。经过2周停药恢复，高剂量组的生化指标恢复不佳，而中、低剂量组则恢复良好。病理学检查结果表明，高、中剂量组大鼠的肝脏、肾脏出现肿胀淤血，高剂量大鼠的肝脏表面有水泡样病灶。结果表明，蟾酥微丸的急性毒性较小，安全性较高；大剂量长期使用可导致肝脏、肾脏损伤，故临床应用要注意剂量和疗程。

Acute and Sub-chronic Toxicity Study of Chansu Pellets

The aim of the experiment was to observe the acute toxicity and the long-term toxicity of Chansu pellets in mice, and to evaluate its safety and provide the theoretical basis for clinical use. Kunming mice were selected for acute toxicity test. The acute toxicity of Chansu pellets was determined by oral administration to mice twice. In the sub-chronic toxicity test, 120 SD rats were divided into low, middle and high dose groups and the control group (the same volume of distilled water) intragastric administration. Respectively, after 28 d of continuous administration and 2 weeks after drug withdrawal, the rats were weighed, and 20 rats (10 mice remaining after cessation of administration) in each group were sacrificed at random. The hematological and biochemical parameters were measured and the histopathological examination was performed. In the acute toxicity, time of death concentrated in 1 to 4 h. LD₅₀ was 13.21 g/kg. In the sub-chronic, after 28 d of continuous dosing, the body weights of male rats of high dose group and the control group were extremely significantly different (P <0.01). Aspartate aminotransferase and alkaline phosphatase of high dose group were extremely significantly different (P <0.01) compared with control group. Kidneys coefficients of high and middle dose groups compared with control group were extremely significantly different (P <0.01). After two weeks the withdrawal recovery, biochemical indicators of high dose group's recovery was not good. Middle and low dose groups had good recovery. Pathological examination showed that high and middle dose groups' rat liver and kidney swelling congestion. High dose rat liver surface were blister-like lesions. The results showed that Chansu pellets were less acute toxicity. Long-term use of large doses could cause liver and kidney damage. Therefore, we should pay attention to dose and duration of treatment in clinical application.