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blank group,the rats in the total ethanol extract group and ethyl acetate fraction group showed poisoning behavior and activity
characteristics such as mental depression,decreased activity and diet,thin stool and decreased body mass. The mental state of the
rats in the petroleum ether fraction group,n-butanol fraction group and water fraction group were slightly worse than that in blank
group,and slightly decreased activity and diet as well as thin stool,and slowly increased body mass were found;however,there
was no significant difference in anal temperature in each group. After 2 weeks of administration,the renal index in total ethanol
extract group,the serum levels of N-acetylglucosaminidase(NAG),urea nitrogen(BUN)and creatinine(Cr)in total ethanol
extract group and ethyl acetate fraction group,serum level of NAG in n-butanol fraction group and serum level of Cr in water
fraction group,as while as NAG levels in urine of rats in total ethanol extract group and petroleum ether fraction group,NAG and
urinary protein levels in urine of rats in ethyl acetate fraction group were increased significantly(P<0.05 or P<0.01). In the
pathomorphological observation,renal tubules showed different degrees of unclear structure,cell swelling and a few cell necrosis
in the total ethanol extract group,petroleum ether fraction group and ethyl acetate fraction group,accompanying by glomerular
pyknosis,renal tubular sclerosis and inflammatory cell infiltration,compared with blank group. After drug withdrawal,the mental
state of rats in the administration groups were significantly improved,the amount of activity and diet increased,and the stool
tended to be normal. Two weeks after drug withdrawal and recovery,the levels of above indexes in serum and urine of rats in
administration groups returned to be close to that in blank group(P>0.05);the glomerular structure of rats in each administration
group gradually recovered clearly,and cell swelling and inflammatory cell infiltration were rare in total ethanol extract group,
petroleum ether fraction group and ethyl acetate fraction group. CONCLUSIONS The total ethanol extract,petroleum ether fraction
and ethyl acetate fraction of Miao medicine W. indica have certain nephrotoxicity and reversibility. The toxic component may be fat
soluble.
KEYWORDS Wikstroemia indica;Miao medicine;nephrotoxicity;total ethanol extract;ethyl acetate fraction;petroleum ether
fraction;rat
苗药了哥王是瑞香科植物南岭荛花Wikstroemia in- 平仪器仪表厂;Targin VX-02 型多管涡旋振荡器购自北
dica(L.)C. A. Mey.的根及根皮。该药始载于《岭南采药 京踏锦科技有限公司;MIKRO 220R型低温高速离心机
录》,性味苦寒、微辛,有毒,具有清热解毒、消肿散结、止 购自德国 Hettich 公司;Sorvall RC 6+离心机购自美国
痛等功效,主要用于治疗瘰疬、痈肿、风湿痛、百日咳、跌 Thermo Fisher Scientific公司;202-3AB 型电热恒温干燥
打损伤等 。现代研究表明,了哥王具有抗菌、抗炎镇 箱购自天津市泰斯特仪器有限公司;BJ1 型不锈钢代谢
[1]
痛、抗病毒、抗肿瘤、抗疟、利尿、镇咳祛痰、降低心肌耗 笼购自湖南长沙市天勤生物技术有限公司。
氧量和改善心肌营养性血流量等药理作用 [2-4] ,常用于 1.2 主要药品与试剂
临床治疗慢性支气管炎、急慢性感染性炎症、颈淋巴结 了哥王药材于2019年12月购自广西壮族自治区玉
肿大、乳腺炎、肝炎、肝硬化、肝腹水、肾炎、肢体疼痛、带
林市玉州区玉林银丰国际中药港,经贵州中医药大学药
状疱疹、皮下剥离伤、坐骨神经痛及辅助治疗多种癌症
学院李玮教授鉴定为真品。N-乙酰氨基葡萄糖苷酶
(如乳腺癌、恶性淋巴癌、肺癌及各种体表癌) [5-9] 。该药
(N-acetylglucosaminidase,NAG)、血尿素氮(blood urea
疗效确切,但毒性较大,在安全性方面存在较大问题,
nitrogen,BUN)、尿蛋白、肌酐(creatinine,Cr)试剂盒均
《生草药性备要》《岭南采药录》《广西中药志》《南宁市药
购自南京建成科技有限公司,批号分别为 20190512、
物志》等著作均明确记载了哥王“大毒”或“有毒”。另
20190515、20190512、20190510;甲醛购自重庆茂业化学
外,本课题组在前期实验中对其提取物进行了急性毒性
试剂有限公司,批号为 20181216;二甲苯购自重庆川东
研究,发现其乙醇总提取物、石油醚部位和乙酸乙酯部
化工有限公司,批号为 200180610;苏木精、伊红染料均
位均有比较大的毒性 ,同时也对其炮制工艺、炮制前
[10]
后药效和毒性变化等进行了探讨 [11-16] 。为进一步明确 购自北京索莱宝科技有限公司,批号分别为 G1140、
了哥王的毒性部位、毒性作用脏器和毒性作用机制,本 G1120;戊 巴 比 妥 钠 购 自 美 国 Sigma 公 司 ,批 号 为
课题组对其肾毒性进行研究,以期为了哥王的毒性作用 922L0310;其余试剂均为分析纯,水为蒸馏水。
机制及临床用药提供参考。 1.3 动物
1 材料 本研究所用实验动物为SPF级SD大鼠,雌雄各半,
1.1 主要仪器 体质量为(200±20)g,购自湖南长沙市天勤生物技术有
ADVIA 1800型全自动生化分析仪购自德国Siemens 限公司,动物生产许可证号为 SCXK(湘)2019-0014,动
公司;BX53F 型光学显微镜购自日本 Olympus 公司; 物合格证号为 43000200002163。所有大鼠均饲养于 12
KD-3368 旋转型组织切片机购自浙江省金华市科迪仪 h 光照/12 h 避光循环、温度(25±1)℃、相对湿度(50±
器设备有限公司;FA2004 型电子分析天平购自上海衡 10)%的动物房内,自由摄食、饮水。
·420 · China Pharmacy 2022 Vol. 33 No. 4 中国药房 2022年第33卷第4期