苗药了哥王“汗渍法”炮制前后抗小鼠免疫性炎症的“量-效-毒”关系研究
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篇名: 苗药了哥王“汗渍法”炮制前后抗小鼠免疫性炎症的“量-效-毒”关系研究
TITLE: Correlation Study of “Dose-effect-toxicity”of Miao Medicine Wikstroemia indica on Anti-immune Inflammation of Mice before and after Processed by “Sweat Soaking Method ”
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、2.6g/kg)和阳性组(环磷酰胺,36.4mg/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20mL/kg,每日1次,连续5d。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。
ABSTRACT: 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 given 1% 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 intrag astrically,oncea day ,for consecutive 5 d. A fter last medication ,ear swelling degree of mice were recorded ;the inhibition rate of swelling degree, half effective dose (ED50) and 95% confidence 158-02-32); 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 1161472062@qq.com 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(0.076 8,0.282 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 groups 2-6),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 .
期刊: 2020年第31卷第06期
作者: 郑传奇,冯果,李玮,周志容,许琴,李志平,易懂斌,李金徽
AUTHORS: ZHENG Chuanqi ,FENG Guo,LI Wei,ZHOU Zhirong ,XU Qin,LI Zhiping ,YI Dongbin ,LI Jinhui
关键字: 了哥王;汗渍法;免疫性炎症;剂量;药效;毒性
KEYWORDS: Wikstroemia indica ;Sweat soa king method ;Immune inflammation ;Dose;Effect;Toxicity
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