摘要
目的研究五子衍宗方(WP)对环磷酰胺(CTX)致肝损伤的保护作用及其机制,以期为临床治疗提供借鉴。方法 2015年9月—2016年6月,将8周龄SPF级BALB/c雄性小鼠40只随机分为正常对照组、模型对照组、WP低剂量组、WP高剂量组,每组10只。应用WP提取黄酮类化合物并将其溶于1%羧甲基纤维素钠(CMCNa),WP低剂量组和WP高剂量组提前3 d分别给予黄酮类化合物140、280 mg/kg,灌胃给药30 d,1次/d;从第3天开始,除正常对照组腹腔注射等量0.9%氯化钠溶液外,其余各组均腹腔注射CTX 50 mg/kg造模,每隔2 d注射1次,共10次。模型对照组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平与正常对照组比较有统计学差异提示造模成功。最后一次注射CTX 12 h后眼球取血、脱臼处死小鼠。检测血清ALT、AST水平;取肝脏,计算肝脏系数,HE染色法观察肝组织形态学表现,检测肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果模型对照组小鼠血清ALT、AST水平高于正常对照组(P<0.01);WP低剂量组、WP高剂量组小鼠血清ALT、AST水平低于模型对照组(P<0.05)。模型对照组肝脏系数高于正常对照组、WP低剂量组、WP高剂量组(P<0.01)。模型对照组小鼠肝小叶和肝索排列混乱,肝细胞肿胀明显并伴有坏死,胞质疏松。WP低剂量组、WP高剂量组肝小叶排列较整齐,肝细胞肿胀和胞质疏松程度较模型对照组明显减轻,肝细胞形态均匀,排列规整。模型对照组肝组织SOD水平低于正常对照组、WP低剂量组、WP高剂量组,MDA水平高于正常对照组、WP低剂量组、WP高剂量组(P<0.05)。结论 WP对CTX所致肝损伤具有良好的保护作用,其机制可能与提高机体的抗氧化能力,清除体内自由基有关。
Objective To study the protective effect and mechanism of Wuzi - Yanzong prescription （WP） against the liver injury induced by cyclophosphamide （CTX） , so as to provide a reference for clinical treatment of the disease. Methods From September 2015 to June 2016, 40 8 - week - old SPF grade male BALB/e mice were randomly divided into normal control group, model control group, WP low- dose group, and WP high -dose group, with 10 mice in each. Flavonoids solution was made by dissolving the flavonoids extracted from WP in 1% CMC - Na. WP low - dose and high - dose groups were respectively intragastrically administered with flavonoids solution 140 mg/kg, 280 mg/kg, once a day for 30 days from the 1st day of intervention. For modeling, from the 3rd day of intervention, mice in the control group were given intraperitoneal injection of 0. 9% sodium chloride solution, while those in the other groups received intraperitoneal injection of CTX 50 mg/kg, once three days for 10 times. Successful modeling was considered when the levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the model control group were statistically different from those in the normal control group. Twelve hours after the last time of injection, all the mice were sacrificed by cervical dislocation after taking blood from the eyeball. The serum levels of ALT and AST were detected, the liver was obtained to calculate the liver index, to observe the tissue morphology changes after HE staining and to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissues. Results The serum ALT and AST levels in the model control mice were higher than those in the normal control group （ P 〈 0. 01 ） . The serum ALT and AST levels in the WP low - dose and high - dose groups were lower than those in the model control group （P 〈0.05） . The liver index in the model control group was higher than that in the other 3 groups （P 〈0.01 ） . In the model control group, the hepa
出处
《中国全科医学》
CAS
北大核心
2017年第27期3426-3430,共5页
Chinese General Practice
基金
国家自然科学基金资助项目(81573931
81373881
81503334)
三峡大学人才科研启动基金(KJ2014B067)
关键词
药物性肝损伤
环磷酰胺
药理作用分子作用机制
五子衍宗方
Drug - induced liver injury
Cyclophosphamide
Molecular mechanisms of pharmacological action
Wuzi - yanzong prescription
