000001b2_伽伯-药物安全.docVIP

Rhubarb caused reverse responses on immature and aged rats: in a safety view Wang Jia-bo, Kong Wei-jun, Xiao Xiao-he*, Zhao Yan-ling, Wang Hong-juan, Zhao Hai-ping, Zhang Lin, Jin Cheng, Fang Fang, Chu Xiao-hui China Military Institute of Chinese Materia Medica, 302 Military Hospital, Beijing 100039, PR China Abstract Aim of the Study: Rhubarb is generally used to people of broad age, but diverse responses of people at different age to rhubarb were little clarified. In this study, an attempt at animal level was made to access the safety of rhubarb to both immature and aged rats to provide some references for its clinical usage. Materials and Methods: Histopathologic and biochemical examinations were performed to investigate any toxic potential of rhubarb covering a broad dosage range. Results: Within the five weeks’ experiment, no death was observed in immature rat control groups, while 23.3% subjects died in aged rat groups with rhubarb treatment. Dosage-dependent incidences of renal lesion were observed in both immature and aged rats, while hepatic lesions were only observed in aged rats associated with increase of interleukin-6 and interleukin-8. Increased incidences of Kupffer cells and lymphocytic infiltration were also found at hepatic sinusoid of rats with rhubarb treatment. Such changes recovered after drug withdrawal for 1 month. Conclusions: Elderly subjects were much more susceptible to the toxicity of high-dosage rhubarb, which drove rigorous consideration on rational use of rhubarb to aged people. The identified age-related hepatotoxic process of rhubarb might involve inflammatory mechanism mediated by interleukins. Key words: Rhubarb; safety evaluation; age; hepatotoxicity; nephrotoxicity; interleukin  幼年和老年大鼠对大黄的耐受性差异研究 王伽伯, 孔维军, 肖小河*, 赵艳玲, 王红娟, 赵海平, 张琳, 金城, 方芳, 楚笑辉 (解放军第三〇二医院全军中药研究所 北京 100039) (2.57，10.26，40 g/kg）大黄后一般状态、生化指标和组织病理的改变。结果：幼年大鼠连续给予不同剂量大黄总提物5周后，均无死亡例发生，而老年大鼠三个剂量组有23.3%的动物死亡，并主要发生在高剂量组。大黄剂量依赖性的肾损伤在幼年和老年大鼠均可观测到；而大黄引起的肝损伤仅在老年大鼠组