蒙药“诃子解草乌毒”减毒存效机理的代谢组学

目的：从代谢组学的角度,采用高效液相与质谱联用的方法研究诃子对于生草乌的"减毒存效"作用机制。方法：将小鼠随机（数字表法）分为空白组、生草乌组、诃子制草乌组、生草乌-诃子3∶1配伍组、生草乌-诃子1∶1配伍组、生草乌-诃子1∶3配伍组、阳性药组,按0.12 g·kg^-1的剂量给药7 d,分别进行棉球肉芽肿试验、二甲苯耳肿胀试验、醋酸扭体试验及热板试,比较每组小鼠肉芽肿胀率、耳肿胀率、扭体次数及舔足潜伏期;将大鼠按以上方法随机分组,按0.12 g·kg^-1的剂量给药4周,通过SIMCA-P软件分析生草乌导致大鼠毒性作用的生物标志物及代谢通路,通过试剂盒检测每组大鼠血清中谷草转氨酶、谷丙转氨酶、肌红蛋白和肌钙蛋白的含量来评估生草乌对大鼠心脏和肝脏的毒性作用。结果：与空白组相比,各实验组都具有明显的抑制肉芽肿胀及耳肿胀效果（P<0.05）,扭体次数明显降低（P<0.05）,舔足潜伏期明显延长（P<0.05）;与阳性药组相比,结果无明显差异;生草乌导致大鼠毒性代谢通路有酰胺tRNA的生物合成,组氨酸代谢,甘氨酸、丝氨酸、苏氨酸代谢,甲烷代谢,乙醛酸和二羧酸代谢,丙氨酸、天冬氨酸、谷氨酸代谢6条代谢通路;生草乌会使大鼠血清中谷草转氨酶、谷丙转氨酶、肌红蛋白和肌钙蛋白的含量明显升高（P<0.05）,诃子可以降低谷草转氨酶、谷丙转氨酶、肌红蛋白和肌钙蛋白的含量。结论：诃子对于生草乌具有"减毒存效"的作用。

The metabonomics for mechanism of toxicity reduction and effect preservation for the Mongolian medicine “Aconitum Detoxification by Terminalia”

OBJECTIVE To use HPLC and mass spectrometry method to study the mechanism for Terminalia to reduce toxicity and preserve effect of Aconitum. METHODS Mice were randomly divided into control group, raw Terminalia group, Aconitum-prepared Terminalia group, 3:1 Terminalia-Aconitum group,1:1 Terminalia-Aconitum group, 1:3 Terminalia-Aconitum group and positive drug group,according to the dose of 0.12 g·kg^-1 administered for 7 days, respectively, granuloma test, xylene induced ear swelling test and acetic acid writhing test and hot plate test, comparison of mice granulation swelling, ear swelling, writhing and licking latency; the rats were randomly divide, according to 0.12 g·kg^-1 the dose around, obtained lead toxicity in rats of biomarkers and metabolic pathways by SIMCA-P software, and evaluate the toxicity of Radix Aconiti kusnezoffii on heart and liver of rats by content kit rats serum aspartate aminotransferase, alanine aminotransferase, myoglobin and troponin. RESULTS compared with the control group, other test groups have obvious inhibitory effect and granulation swelling of ear swelling (P<0.05), the writhing frequency decreased significantly (P<0.05), licking latency was significantly prolonged (P<0.05); compared with the positive group, other test groups inhibited the granulation swelling and ear swelling effect, writhing, no significant difference between the latency of licking foot; through the SIMCA-P software analysis Aconitum lead to toxic effects in rats with metabolic pathways involving the amide tRNA biosynthesis, histidine metabolism, glycine, Serine and threonine metabolism, methane metabolism, glyoxylic acid and two carboxylic acid metabolism, alanine, aspartic acid, glutamic acid metabolism pathway for six days; compared with the blank group, rats serum cTn-I,MB,AST,ALT increased significantly (P<0.05) beacase of Radix Aconiti kusnezoffii, the content of Myrobalam system, but rats serum cTn-I,MB,AST,ALT significantly decreased in the serum of the rats (P<0.05) beacase of Terminalia. CONCLUSION Chebulinic for preserving effects and decreasing toxicity effect of Radix Aconiti kusnezoffii.