青木香炮制前后的药效及毒理学比较研究

目的：研究青木香炮制前后水提物对大鼠的蓄积性毒性作用,及水提物、醇提物的药效学作用。方法：采用小鼠急性毒性和大鼠蓄积性毒性方法观察青木香炮制前后对小鼠急性毒性LD₅₀和对大鼠的慢性蓄积性毒性作用；观察了青木香炮制前后的水煎剂和醇提物对正常和新斯的明诱导的胃肠运动机能亢进小鼠肠肌运动的影响；并观察了对小鼠的镇痛和抗炎作用。结果：生品和炮制品水提物灌胃给药的LD₅₀分别为生药146.45,846.06 g·kg_-1；生品及其炮制品水提物高、中、低3个剂量组,连续给药1个月对大鼠的一般状况和外周血常规和血清生化、脏器系数和病理组织学检查均未见明显改变。连续给药2个月,可见生品的高剂量组的血清生化指标的尿素氮、总胆固醇和碱性磷酸酶明显升高,组织形态学检查部分动物的肝细胞、肾小管和胃黏膜均产生程度不同的损伤。连续给药3个月,生品的中、高剂量组和炮制品的大剂量组均出现了上述脏器程度不同的损伤,可见血清生化指标的肌酐、尿素氮明显升高,肝、肾、胃脏器系数明显增加。但等量的炮制品水提物的毒性明显低于生品；生品和炮制品的水提物、醇提物对正常和新斯的明诱导的小鼠胃肠运动机能亢进均呈现出明显的抑制作用；在小鼠的扭体和热刺激模型上显示出明显的镇痛作用；对二甲苯诱导的小鼠耳廓炎症有显著的抑制作用,在剂量相同的条件下生品、炮制品的药效学作用无明显差异。结论：青木香炮制后急性毒性和慢性蓄积性毒性明显降低,炮制后药效学作用强度不低于生品；水提物药效学作用不及相应剂量的醇提物。

Pharmacodynamic and toxicologic comparative study of crude and processed Radix Aristolochice

OBJECTIVE: To study the accumulated toxic action to bandicoot of aqueous extract of crude and processed Radix Aristolochice and the pharmacodynamic action of aqueous and alcoholic extract of crude and processed Radix Aristolochice. METHOD: The LD50 of acute toxicity to mice and chronic accumulated toxicity to bandicoots of crude and processed Radix Aristolochice were observated. Intestinal and myokinetic influence of normal and revulsive hyperactive gastrointestinal motility of mice induced by neostigmine were observated by giving aqueous extract and alcoholic extract of crude and processed Radix Aristolochice. Relieving pain and eliminating inflammation to mice also were observated. RESULT: The LD50 of aqueous extract of crude and processed Radix Aristolochice were 146. 45, 846.06 g X kg(-1) (equivalently to crude drug) respectively by intragastric administration. Bandicoot' general condition, peripheral blood, serum, organic coefficient, histopathologic examination weren't obvious changes after 1 month administrating aqueous extract of crude and processed drug in three dose. Serum indicators-urea nitrogen, cholesterol total, alkaline phosphatase manifestly were heightened and some animals'hepatic cells, nephric tubules and mucosa emerged differently damage at histomorphology by giving crude high dose after 2 months. Above organs emerged different damage in crude middle and high dose and processed high dose after 3 months and serum indicators- creatinine, urea nitrogen manifestly were increased, the coefficients of liver, kidney and gaster manifestly were heightened. However, the toxicity of identical dose processed product was lower than that of crude one. Aqueous extract and alcoholic extract of crude and processed Radix Aristolochice could obviously inhibite normal and revulsive hyperactive gastrointestinal motility by neostigmine of mice, relieve pain in mouse, stretching and heat stimulation models and inhibite dimethyl benzene-induc mouse, auricle inflammation. Pharmacodynamic action wasnt obvious difference in same dose of crude product and processed one. CONCLUSION: Acute toxicity and chronic accumulated toxicity are stepped down after giving processed Radix Aristolochice, but pharmacodynamic effect wasn t lower. In pharmacodynamic effect, aqueous extract can't compare with alcoholic extract in same dose.