目的 研究不同提取工藝對(duì)炒決明子急性毒性和物質(zhì)基礎(chǔ)的影響，為炒決明子的臨床安全用藥提供依據(jù)。方法 分別制備炒決明子水提物和醇提物，用高效液相色譜法測(cè)定大黃酚和橙黃決明素含量。預(yù)試驗(yàn)結(jié)果表明由于受給藥體積及濃度的限制，難以找出炒決明子水提物組和醇提物對(duì)小鼠的半數(shù)致死量（LD₅₀），進(jìn)行最大耐受量（MTD）或最大給藥量（MFD）的測(cè)定。正常小鼠按性別、體質(zhì)量隨機(jī)分成3組：對(duì)照組、炒決明子水提物組、炒決明子醇提物組，每組20只。水提物組按40.0 mL/kg給藥1次，12 h后無(wú)死亡情況，進(jìn)行第2次給藥。醇提物組按40.0 mL/kg給藥1次，12 h內(nèi)出現(xiàn)死亡情況，不進(jìn)行第2次給藥，對(duì)照組小鼠ig相同體積的水。觀察小鼠體質(zhì)量、飲食、飲水，14 d內(nèi)可能出現(xiàn)的呼吸頻率改變、呼吸困難、動(dòng)度、對(duì)外反應(yīng)情況、排便異常等，檢測(cè)血清天冬氨酸轉(zhuǎn)氨酶（AST）、丙氨酸轉(zhuǎn)氨酶（ALT）、肌酐（Cr）、尿素氮（BUN）水平。結(jié)果 制備的炒決明子水提物按生藥量計(jì)為0.952 g/mL，大黃酚、橙黃決明素分別占生藥的0.145 1%、0.018 5%；制備的炒決明子醇提物按生藥量計(jì)為3.950 g/mL，大黃酚、橙黃決明素分別占生藥的0.144 9%、0.024 8%。炒決明子水提物對(duì)正常小鼠的MFD為114.96 g/kg，相當(dāng)于臨床成年人日用量的588倍；炒決明子醇提物對(duì)正常小鼠MTD為178.40 g/kg，相當(dāng)于臨床成年人日用量的832.5倍。炒決明子水、醇提取物的急毒主要表現(xiàn)為：出現(xiàn)間歇扭體反應(yīng)、便溏、呼吸頻率減慢、呼吸困難、精神萎靡、俯臥昏睡等，其中便溏現(xiàn)象尤為明顯，且醇提物>水提物。給藥后，炒決明子水提物組和醇提物組小鼠的ALT、AST、BUN、Cr指標(biāo)升高，與對(duì)照組比較，水提物組ALT、BUN、Cr水平呈顯著性差異（P<0.01、0.001），AST未見(jiàn)顯著性差異；醇提物組ALT、BUN、Cr水平呈顯著性差異（P<0.001），AST未呈現(xiàn)顯著性差異。結(jié)論 大劑量炒決明子水、醇提物對(duì)正常小鼠的肝、腎功能均有影響，其中對(duì)腎臟的影響較為嚴(yán)重；臨床應(yīng)用中，盡量選用炒決明子水提工藝以保證安全有效。

Objective To study the relationship between acute toxicity and material basis of the roasted seeds of Cassia obtusifolia by different extraction techniques,and provide a basis for safe clinical use.Methods The water extract and alcohol extract of the roasted seeds of C.obtusifolia was prepared,the content of chrysophanol and aurantio-obtusin in different extracts was determinated by HPLC.Pre-test results showed that it was difficult to find out the LD₅₀ of water extract and alcohol extract in mice due to the limitation of drug volume and concentration,the maximum tolerable dose (MTD) or the maximum dose (MFD) were determined.Normal mice were randomly divided into three groups according to sex and body weight:control group,water extract group and alcohol extract group,with 20 mice in each group.In the water extract group,40.0 mL/kg was administered once,and no death occurred 12 h later,and the second dose was administered.The ethanol extract group was given 40.0 mL/kg once,and death occurred within 12 h,and no second dose was given.The mice in the control group were received the same volume of water by ig.The changes of body weight,diet,drinking water,respiratory frequency,dyspnea,motility,external reaction and abnormal defecation were observed within 14 d.The levels of serum aspartate aminotransferase (AST),alanine aminotransferase (ALT),creatinine (Cr),urea nitrogen (BUN) were detected.Results The water extract was 0.952 g/mL according to the amount of crude drugs,chrysophanol and aurantio-obtusin accounted for 0.1451% and 0.0185% in water extract,respectively;The alcohol extract was 3.950 g/mL according to the amount of crude drugs,chrysophanol accounted for 0.1449%,aurantio-obtusin accounted for 0.0248%;The MFD of the roasted seeds of C.obtusifolia water extract was 114.96 g/kg for normal mice,which was 588 times of the daily dosage per kilogram of body weight of 70 kg adults.The MTD of roasted seeds of C.obtusifolia ethanol extract was 178.40 g/kgfor normal mice,which was 832.5 times the daily dosage per kilogram of body weight of 70 kg adults.The acute poison of water and alcohol extract of the roasted seeds of C.obtusifolia was mainly manifested as follows:intermittent twisting reaction,loose stool,slow breathing rate,dyspnea,depression,prone to lethargy,etc,the phenomenon of loose stool was particularly obvious,and ethanol extract > water extract.The ALT,BUN,Cr levels increased in aqueous extract group and alcohol extract group.Compared with control group,the aqueous extract group ALT,BUN,Cr levels show very significant difference (P<0.01 and 0.001),AST did not show significant difference.The ALT,BUN and Cr levels of alcohol extract group were supremely significant different (P<0.001),AST was not significantly different.Conclusion High dose of water and alcohol extracts of the roasted seeds of C.obtusifolia have effects on liver and kidney function of normal mice,among which the effects on kidney are more serious.In clinical application,the water extraction process of the roasted seeds of C.obtusifolia should be selected as far as possible to ensure its safety and effectiveness.

國(guó)家公益性行業(yè)科研專項(xiàng)（201507004-03）；山東省泰山學(xué)者工程專項(xiàng)經(jīng)費(fèi)資助（ts201511107）