血必净注射液的功效安全性再评价

Function and safety re-evaluation of Xuebijing injection, a traditional Chinese medicine injection

目的使用玉米低营养小鼠模型结合损益指数-累计积分（BDI-GS）体系评价生理剂量下中药血必净注射液的补益和健康效应，考察该体系在临床中药注射液功效及安全性再评价中应用的科学性和实用性。方法将生长期健康ICR 小鼠随机分为空白对照组和低、中、高剂量组，以玉米饲料喂养小鼠。每天腹腔注射给药1 次，空白对照组小鼠注射0.4 ml 0.9%氯化钠注射液，低、中、高剂量组小鼠分别注射0.2、0.4、0.6 ml 血必净注射液，连续给药7 d。第8 天完整剖取心脏、肺脏、胸腺、脾脏、胰腺、肝脏、肾脏、性腺及股骨9 种脏器，计算9 种脏器的质量BDI、系数BDI 及对应的质量BDI 累计积分（GSW）、系数BDI累计积分（GSI），并测定血清生化指标。结果血必净注射液在生理剂量下连续用药安全性良好，对小鼠脾脏及性腺具有一定的补益及健康效应，对其余脏器损害轻微，表现在9 种脏器的质量和系数BDI 值均＞0.90，且GSW 和GSI 值均＞9.0 的基本值，并呈剂量依赖性增高。此外，高剂量组总蛋白水平（（47.6±4.30）g/Ｌ）明显高于空白对照组（（43.18±2.60）g/Ｌ），差异具有统计学意义（P＜0.05）。结论血必净注射液正常用药风险低，在生理剂量下是安全的，且本研究设计的高剂量安全性更好。玉米低营养小鼠模型结合BDI-GS 体系可用于临床中药注射剂功效及安全性再评价。

Objective To evaluate the tonic and health effects of Xuebijing injection, a traditional Chinese medicine injection, by means of corn low-nutritional mice model combined with benefit-damage index-general score （BDI-GS） evaluation system under a physiological dosage. Further, to investigate the scientific and practical benefits of the evaluation system in efficacy and safety re-evaluation of clinical traditional Chinese medicine injections.Methods Healthy ICR mice during growth period were randomly divided into blank control group and low, middle and high dose groups. All the mice were fed with corn diets, and treated by intraperitoneal injection once a day. The mice in the blank control group were injected with 0.4 ml 0.9% sodium chloride injection, and the mice in the low,medium and high dose groups were injected with 0.2, 0.4 and 0.6 ml Xuebijing injection, respectively, for seven days.On the 8th day, the mice were killed, dissected, and took nine kinds of organs including heart, lung, thymus, spleen,pancreas, kidney, gonad and femur. The weight BDI, index BDI and the corresponding weight BDI general score （GSW） and index BDI general score （GSI） were calculated, and the serum biochemical parameters were measured.Results Under the physiological dose, Xuebijing injection shows good safety of continuous infusion, tonic and health effects, and slight damages on the rest of organs. More specifically, the values of weight BDI and index BDI were all higher than 9.0, and values of GSW and GSI were all higher than the basic value of 9.0. Furthermore, these parameters increased in a dose-dependent manner. In addition, the total protein level of （47.6 ± 4.30） g/L in the high dose groups was significantly higher than （43.18 ± 2.60） g/L in the blank control group （P〈0.05）. Conclusions The Xuebijing injection has a lower risk for conventional usage. This injection is safe under the physiological dosage and much safer in higher dosage designed in this study. The low-nutritional model combined with BDI-GS evaluation system can be used for re-evaluating the function and safety of clinical traditional Chinese medicine injections.