附子不同炮制品对风湿寒痹类风湿关节炎大鼠的急性毒性试验研究

目的:比较附子不同炮制品对风湿寒痹类风湿关节炎(RA)大鼠的急性毒性。方法:通过高效液相色谱法测定各炮制品水提物中6种酯型生物碱的含量;采用完全弗氏佐剂结合风寒湿因素建立风湿寒痹RA大鼠模型,单次灌胃盐附子水提物(生药量5.81、7.00、8.43、10.16、12.24、14.75 g/kg),通过改良Bliss法计算半数致死量(LD50);单次灌胃炮天雄、刨附片、白附片、黑顺片水提物,分别测定最大给药量(MFD),通过观察给药后体重、摄食量、饮水量的变化,计算主要脏器系数,观察HE染色组织病理学变化,检测血生化、血常规指标进行急性毒性评价。结果:黑顺片、盐附子水提物所含双酯型生物碱含量相对较高,炮天雄水提物中单酯型生物碱含量较高。盐附子水提物灌胃RA大鼠的LD50为生药量8.134 g/kg,炮天雄、刨附片、白附片、黑顺片水提物灌胃RA大鼠的MFD分别为生药量28.8 g/kg、46.2 g/kg、46.8 g/kg、63.4 g/kg。与模型对照组比较,8.43 g/kg盐附子组血小板(PLT)含量显著升高(P<0.01);黑顺片63.4 g/kg组总蛋白(TP)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平和淋巴细胞百分比(LY)明显降低,碱性磷酸酶(AKP)水平、中性粒细胞百分比(GR)、单核细胞百分比(MO)明显升高(P<0.05或P<0.01);刨附片46.2 g/kg组AKP水平明显升高(P<0.05)。结论:盐附子水提物对风湿寒痹RA大鼠的毒性较大,炮天雄、刨附片、白附片、黑顺片水提物对风湿寒痹RA大鼠无明显毒性。

Acute Toxicity of Different Processed Products of Radix Aconiti Lateralis Preparata in Rheumatoid Arthritis Rats with Fengshihanbi syndrome

Objective: The aim of this paper was to observe the acute toxicity of different processed products of Radix Aconiti Lateralis Preparata in rheumatoid arthritis rats. Methods: The contents of 6 ester alkaloids in aqueous extracts from different processed products of Radix Aconiti Lateralis Preparata were determined by HPLC. The RA rat model with Fengshihanbi syndrome was established by complete Freund’s adjuvant combined with Feng-Han-Shi factors. Yanfuzi aqueous extracts were administered once in each group(5.81,7.00,8.43,10.16,12.24,14.75 g/kg) and the median lethal dose(LD50) was calculated by modified Bliss method. After single oral administration of Paotianxiong, Paofupian, Baifupian and Heishunpian aqueous extracts, the maximal feasible doses(MFD) were determined. The changes of body weights,the food consumption and the water consumption were recorded and the organ coefficients were calculated, histopathological changes were observed by HE staining, blood biochemistry and blood routine were detected to evaluate the acute toxicity. Results: The contents of diester alkaloids in Heishunpian and Yanfuzi aqueous extracts were higher than others,while the content of monoester alkaloids in Paotianxiong aqueous extract was higher than others. The LD50 of the RA rats administered with Yanfuzi aqueous extract was 8.134 g/kg. The MFDs of the RA rats administered with Paotianxiong, Paofupian, Baifupian and Heishunpian aqueous extract were 28.8 g/kg, 46.2 g/kg, 46.8 g/kg and 63.4 g/kg, respectively. Compared with the model group, the content of platelet(PLT) was obviously increased in 8.43 g/kg Yanfuzi group(P<0.01), lymphocytes percentage(LY), the levels of total protein(TP), alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were obviously decreased in Heishunpian group, the level of alkaline phosphatase(AKP), neutrophilic granulocyte percentage(GR) and monocytes percentage(MO) were obviously increased in Heishunpian group(P<0.05 or P<0.01). The AKP level was obviously increased in Paofupian group(P<0.05). Conclusion: Yanfuzi aqueous extract has the significant toxicity in RA rats with Fengshihanbi syndrome, while Paotianxiong,Paofupian,Baifupian and Heishunpian aqueous extracts have no obvious toxicity.