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目的:观察不同浓度苍耳子水萃取物对大鼠肝脏功能与形态的影响,为临床安全使用苍耳子提供实验依据。方法:取苍耳子碎粉22 kg,用65%乙醇提取,用石油醚、乙酸乙酯、正丁醇萃取,回收有机溶剂后得到水萃取物743.6 g。水提取物用含3%吐温80生理盐水配制成28.00 mg/mL和1.12 mg/mL混悬液。144只SPF级雄性SD大鼠,体重(200±10)g,用随机数字表法分为苍耳子水萃取物高剂量组、低剂量组和对照组,每组48只。高、低剂量组分别给予28.00 mg/mL和1.12 mg/mL苍耳子水萃取物混悬液2.5 mL每日2次灌胃,对照组以3%吐温80生理盐水2.5 mL灌胃;均连续28 d。分别于给药开始后7、142、12、8 d和停药后71、4 d观察大鼠被毛、摄食量和活动情况,测量大鼠体重,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)水平,取肝脏计算肝脏指数(肝重/体重×100%),进行肝脏病理分级和评分。结果:苍耳子水萃取物高剂量组大鼠给药28 d内先后出现竖毛、脱毛、疲倦少动、摄食量减少、对外界刺激反应缓慢等症状;低剂量组仅少数大鼠出现少动喜卧、精神萎靡等症状。停药14 d后高剂量组大鼠活动量和摄食量均增加,少动喜卧症状减轻,被毛光泽度恢复。给药212、8 d和停药7 d时,高剂量组大鼠体重([10.5±4.2)(、10.2±3.1)(、12.1±4.5)g]明显低于低剂量组([15.3±2.1)(、16.7±4.2)(、17.6±3.2)g]和对照组([18.6±3.4)(、20.5±5.2)(、19.6±2.5)g],血清ALT([42.8±3.2)(、49.3±5.9)(、43.2±3.2)U/L]和AST([108.8±11.7)(、119.8±16.3)(、110.5±17.6)U/L]水平均明显高于低剂量组([33.7±4.60)(、34.8±5.4)(、33.5±4.9)U/L(,94.7±12.6)(、95.4±10.7)(、96.8±12.8)U/L]和对照组([31.2±4.3)(、32.5±6.3)、(31.7±5.7)U/L(,92.3±16.2)(、92.9±20.3)(、93.7±16.3)U/L;]血清AKP([197.2±25.7)(、210.4±41.8)(、189.3±17.6)U/L]水平明显高于低剂量组([174.3±22.6)(、175.3±27.4)(、176.3±22.8)U/L]和对照组[(171.3±25.6)、(172.5±28.7)(、172.8±26.3)U/L;]给药21、28 d和停药7 d时高剂量组肝脏指数(4.2±0.45、.0±0.7、4.9±0.3)明显高于低剂量组(3.4±0.63、.6±0.53、.9±0.6)和对照组(3.0±0.4、3.2±0.3、3.4±0.5);给药14、21、28d和停药7d时高剂量组大鼠肝脏病理评分中位数分别为(1.0、1.5、3.0、1.5),明显高于低剂量组(0.2、0.5、0.9、0.5)和对照组(0.1、0.1、0.2、0.1)。以上各指标高剂量组与低剂量组、对照组间差异均有统计学意义(P<0.05,P<0.01);而低剂量组与对照组间差异均无统计学意义(均P>0.05)。结论:苍耳子水萃取物致大鼠肝损害与其浓度和作用时间有关;大剂量和长时间用药可加重肝损害。
OBJECTIVE: To observe the effects of different concentrations of water of Xanthium sibiricus on liver function and morphology in rats, and to provide experimental evidence for the safe use of Xanthium sibiricus. Method: Take cocklebur powder 22 kg, extracted with 65% ethanol, extracted with petroleum ether, ethyl acetate and n-butanol, and then the organic solvent was recovered to obtain 743.6 g of water extract. Water extracts were formulated into 28.00 mg / mL and 1.12 mg / mL suspensions in 3% Tween 80 containing saline. A total of 144 SPF male Sprague-Dawley (SD) SD rats weighing 200 ± 10 g were divided into high dose group, low dose group and control group with 48 animals in each group by random number table. High and low dose groups were given 28.00 mg / mL and 1.12 mg / mL Xanthium aqueous extract suspension 2.5 mL orally 2 times a day, the control group 3% Tween 80 saline 2.5 mL intragastrically; both were Continuous 28 d. The body weight, body weight and serum alanine aminotransferase (ALT) were measured at 7, 142, 12 and 8 d after administration and 71, , Aspartate aminotransferase (AST) and alkaline phosphatase (AKP) were measured. The liver index (liver weight / body weight × 100%) was taken for liver pathological grade and score. Results: The rats in the high-dose Xanthium sibiricum extract group developed symptoms such as vertical hair, hair removal, less tiredness, less food intake and slow response to external stimuli within 28 days after administration. In the low-dose group, only a few rats appeared less Moving hi horizontal, sluggish and other symptoms. After 14 days of withdrawal, the activity and food intake of rats in high-dose group were increased, the symptoms of less-moving hi-lieder were relieved, and the luster of hair was recovered. The body weight ([10.5 ± 4.2] (10.2 ± 3.1) (12.1 ± 4.5) g] in the high dose group was significantly lower than that in the low dose group ([15.3 ± 2.1 ), (16.7 ± 4.2), (17.6 ± 3.2) g and control group (18.6 ± 3.4, 20.5 ± 5.2, 19.6 ± 2.5, ± 5.9, 43.2 ± 3.2 U / L, and AST were significantly higher than those in the low-dose group ([33.7 ± 4.60 (119.8 ± 16.3), 110.5 ± 17.6 U / L ), (34.8 ± 5.4), (33.5 ± 4.9) U / L, 94.7 ± 12.6, 95.4 ± 10.7, 96.8 ± 12.8 U / L and 31.2 ± 4.3, The serum levels of AKP ([197.2 ± 25.7] (210.4 ± 41.8) (, 210.4 ± 41.8) and (31.7 ± 5.7) U / L and 92.9 ± 20.3 and 93.7 ± 16.3 U / , 189.3 ± 17.6 U / L] were significantly higher than those in the low-dose group ([174.3 ± 22.6], 175.3 ± 27.4, 176.3 ± 22.8 U / L and 171.3 ± 25.6, ± 28.7), (172.8 ± 26.3) U / L;] The liver index (4.2 ± 0.45, .0 ± 0.7, 4.9 ± 0.3) in the high-dose group was significantly higher than that in the low dose group (3.4 ± 0.63, .6 ± 0.53, .9 ± 0.6) and control group (3.0 ± 0.4,3.2 ± 0.3,3.4 ± 0.5). At the 14th, 21st, 28th day and 7th day after administration, the high dose group rats liver The median pathological score was (1.0,1.5,3.0,1.5), significantly higher than the low dose group (0.2,0.5,0.9,0.5) and the control group (0.1,0.1,0.2,0.1). There was significant difference between the high-dose group and the low-dose group and the control group (P <0.05, P <0.01), but there was no significant difference between the low-dose group and the control group (all P> 0.05) . CONCLUSION: The liver damage induced by water extract of Xanthium sibiricum is related to its concentration and action time; high dose and prolonged administration can aggravate liver damage.