钩藤总碱缓释滴丸的长期毒性实验研究

Experimental study on long-term toxicity of sustained-release dropping pills of Rhynchophylla total alkaloids in rats

目的：探讨钩藤总碱（RTA）缓释滴丸的长期毒性。方法将80只Wister大鼠按体质量随机分为空白对照组、RTA缓释滴丸高、中、低剂量组，每组20只。每天观察大鼠的一般状态、每2周记录一次体质量、日食量。连续灌胃12周后和停药2周后分别检测大鼠白细胞（WBC）、红细胞（RBC）、血红蛋白（Hb）、血小板（PLT）、淋巴细胞（LYM）、中性粒细胞（NEU）等血液学指标及谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（ALP）、尿素氮（BUN）、肌酐（Cr）等生化指标，计算心、脑、肝、肾脏体比值，观察心、脑、肝、肾组织病理学改变。结果连续灌胃12周后， RTA 缓释滴丸高剂量组大鼠饮食减少，体质量增长缓慢；各组大鼠 WBC、RBC、Hb、PLT、LYM、NEU无明显变化；RTA缓释滴丸高剂量组大鼠的ALT、AST和ALP值升高[分别为（77.5±11.9）U/L、（210.4±21.7）U/L、（220.6±19.8）U/L]，与空白对照组[分别为（55.2±12.1）U/L、（180.4±21.3）U/L、（190.3±22.6）U/L]比较，差异有统计学意义（P＜0.05）。RTA 缓释滴丸高剂量组大鼠肝脏的脏体比值（3.86±0.29）较空白对照组（3.52±0.25）升高（P＜0.05），肝脏部分出现变性、灶状坏死。结论 RTA缓释滴丸高剂量长期给药可产生肝毒性。

Objective To observe the long-term toxicity of sustained-release dropping pills of Rhynchophylla total alkaloids in rats.Methods 80 Wistar rats were randomly divided into high dose group, middle dose group, low dose group and normal group. The rats were consecutively drenched for 12 weeks. The general status of the animals was observed daily in medication duration and body weight, daily appetite, quantity were recorded every 2 weeks. All animals were sacrificed on drenched 12 weeks and 2 weeks after discontinuation, then the content of WBC, RBC, Hb, PLT, LYM, NEU and ALT, AST, ALP, BUN, Cr were detected. Ratio of viscera was measured and the major organs were examined by the pathology.Results Continuous intragastric administration for 12 weeks after high dose group rats, poor diet, weight growth was slow;no significant changes of Hematology was found;The ALT, AST and ALP of high dose group rats increased[respectively（77.5±11.9）U/L,（210.4±21.7）U/L,（220.6±19.8）U/L], compared with the blank control group[respectively（55.2±12.1）U/L,（180.4±21.3）U/L,（190.3±22.6）U/L], the difference was statistically significant（P〈0.05）. The ratio of liver body in high dose group（3.86±0.29）was higher than the control group（3.52±0.25）, the difference was statistically significant（P〈0.05）. And liver degeneration, focal necrosis was found.Conclusion The main chronic toxic damage is liver damage caused by sustained-release dropping pills of Rhynchophylla total alkaloids of long-term large delivery.