摘要
目的:探讨苗药了哥王炮制前后抗小鼠免疫性炎症的"量-效-毒"关系。方法:将小鼠分成空白组、模型组、了哥王生品醇提物1~6组、了哥王"汗渍法"炮制品醇提物1~6组(以下分别简称为"生品1~6组""炮制品1~6组",剂量均分别为0.13、0.20、0.26、0.52、1.04、2.6 g/kg)和阳性组(环磷酰胺,36.4 mg/kg),每组10只。除空白组外,其余各组小鼠均以1%2,4-二硝基氟苯-丙酮-麻油混合溶液复制迟发型超敏反应模型。造模后,空白组和模型组小鼠均灌胃等容1.0%羧甲基纤维素钠溶液,各给药组小鼠灌胃相应药液20 mL/kg,每日1次,连续5 d。末次给药后,记录各组小鼠耳肿胀度,并计算生品及炮制品的肿胀抑制率、半数有效剂量(ED50)及其95%置信区间(CI);称定小鼠心、肝、脾、肺、肾的质量,并计算各脏器指数;采用酶联免疫吸附测定法、改良化学氧化法分别检测小鼠血清中炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)]和肝肾功能指标[丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、尿素氮(BUN)、血肌酐(CREA)]水平。结果:与空白组比较,模型组小鼠耳肿胀度显著升高(P<0.05);与模型组比较,了哥王生药及炮制品醇提物各剂量组小鼠耳肿胀度均显著降低(P<0.05),其肿胀抑制率均有随剂量增加而升高的趋势,两者抗小鼠迟发型超敏反应耳肿胀的ED50及95%CI分别为0.2396(0.1290,0.4452)g/kg、0.1473(0.0768,0.2827)g/kg。与空白组比较,模型组小鼠肝指数、血清TNF-α水平均显著升高,肺指数、血清IL-10水平均显著降低(P<0.05);与模型组比较,不同给药组小鼠肝指数(阳性组、生品3组和炮制品1~6组)、血清TNF-α水平(阳性组、生品1~3组及炮制品1~4组)均显著降低,肺指数(阳性组、生品3~6组及炮制品3~6组)、血清IL-10水平(生品1、2、4、5组以及炮制品2~6组)以及ALT、AST、BUN、CREA水平(生品4~6组)和TBIL水平(生品3~6组)均显著升高(P<0.05)。结论:了哥王生品醇提物具有一定的抗免疫炎症活性,且对小鼠具有肝肾毒性,呈一定的"量-效-毒"关系;炮制品醇提物也具有一定的抗免疫炎症活性,但肝肾毒性弱于生品。"汗渍法"具有"存效减毒"的效果。
OBJECTIVE:To investigate the"dose-effect-toxicity"correlation of Miao medicine Wikstroemia indica before and after processed on anti-immnue inflammation of mice. METHODS:Mice were divided into blank group,model group,ethanol extract of W. indica raw product groups 1-6,ethanol extract of W. indica processed product by"sweat soaking method"groups 1-6(hereinafter called"raw groups 1-6""processed groups 1-6"for short,drug dosage were 0.13,0.20,0.26,0.52,1.04,2.6 g/kg),positive group(cyclophosphamide,36.4 mg/kg),with 10 mice in each group. Except for blank group,other groups were given1% 2,4-dinitrofluorobenzene-acetone-sesame oil mixed solution to induce delayed type hypersensitivity model. After modeling,blank group and model group were given constant volume of 1.0% CMC-Na solution intragastrically,and administration groups were given relevant medicine 20 mL/kg intragastrically,once a day,for consecutive 5 d. After last medication,ear swelling degree of mice were recorded;the inhibition rate of swelling degree, half effective dose(ED50) and 95% confidence interval(CI) of raw and processed products were calculated;the weight of heart, liver, spleen, lung and kidney were measured and the indexes of organs were calculated;ELISA and modified chemical oxidation method were used to determine the serum levels of inflammatory factors(TNF-α,IL-10) and liver and renal function indexes(ALT, AST,TBIL,BUN,CREA). RESULTS:Compared with blank group,the degree of ear swelling in the model group was significantly increased(P<0.05). Compared with model group,ear swelling degree of mice were decreased significantly in different doses groups of ethanol extract of raw and processed products of W. indica(P<0.05). The inhibition rate of swelling increased with the increase of dose,ED50 and 95%CI of delayed hypersensitivity ear swelling were 0.239 6(0.129 0,0.445 2)g/kg and 0.147 3(0.0768,0.282 7)g/kg,respectively. Compared with blank group,liver index and serum TNF-α level of mice were increased significantly in model group,while lung index and serum IL-10 level were decreased significantly(P<0.05). Compared with model group,the levels of liver indexes(positive group,raw group 3,processed groups 1-6)and serum TNF-α levels(positive group,raw groups 1-3,processed groups 1-4) were decreased significantly in different administration groups;while the levels of lung indexes(positive group,raw groups 3-6 and processed groups 3-6),serum IL-10 levels(raw groups 1,2,4 and 5,processed groups2-6),ALT,AST,BUN and CREA levels(raw groups 4-6),TBIL levels(raw groups 3-6)were increased significantly(P<0.05). CONCLUSIONS:The ethanol extract of raw product of W. indica has certain anti-inflammatory activity,and has certain hepatorenal toxicity to mice,with certain"dose-effect-toxity"correlation. The ethanol ectract of processed product of W. indica has certain anti-inflammatory activity too,but its hepatorenal toxicity was lower than raw product. The"sweat soaking method"possesses the function of"retaining efficiency and reducing toxicity"for processing W. indica.
作者
郑传奇
冯果
李玮
周志容
许琴
李志平
易懂斌
李金徽
ZHENG Chuanqi;FENG Guo;LI Wei;ZHOU Zhirong;XU Qin;LI Zhiping;YI Dongbin;LI Jinhui(College of Pharmacy,Guizhou University of TCM,Guiyang 550025,China;National Engineering and Technology Research Center of Miao Medicine,Guiyang 550025,China)
出处
《中国药房》
CAS
北大核心
2020年第6期661-665,共5页
China Pharmacy
基金
国家自然科学基金资助项目(No.81760766)
国家中医药管理局“中药炮制技术传承基地建设”项目(No.国中医药科技中药便函[2015]132)
贵州省科技计划项目(No.黔科合基础[2017]1007)
贵州省一流专业(中药学)建设项目(No.黔高教发[2017]158-02-32)
贵州中医药大学科研项目(No.贵中医科院内[2016]40)
贵州中医药大学博士启动基金项目(No.贵中医博士基金[2017]1)。
关键词
了哥王
汗渍法
免疫性炎症
剂量
药效
毒性
Wikstroemia indica
Sweat soaking method
Immune inflammation
Dose
Effect
Toxicity
