橙皮苷衍生物Y-12抑制CYP2E1对CCl_4诱导的小鼠急性肝损伤的保护作用研究  

Protective research of HY-12 inhibiting CYP2E1 on acute liver injury in mice induced by carbon tetrachloride

作　　者：曹雪艳[1,2,3] 李俊[1,2,3] 黄成[1,2,3] 潘苏岩 孟祥波[1,2,3] 张乐天[1,2,3] 

机构地区：[1]安徽医科大学药学院,合肥230032 [2]安徽医科大学安徽省天然药物活性研究重点实验室,合肥230032 [3]安徽医科大学安徽省天然药物活性成分工程技术研究中心,合肥230032

出　　处：《安徽医科大学学报》2016年第5期664-669,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1408085MKL31);国家自然科学基金(编号:81473268)

摘　　要：目的探讨橙皮苷(HDN)衍生物Y-12(HY-12)抑制CYP2E1对四氯化碳诱导的小鼠急性肝损伤的保护作用。方法将70只昆明小鼠随机均分为正常组、模型组、HY-12高、中、低剂量组和阳性对照药(甘草酸二铵组和HDN组)。将小鼠分别以0.5%羧甲基纤维素钠和相应的药物连续灌胃7 d,第7天给药结束后除正常组外,分别向小鼠腹腔注射0.2%CCl_4(0.1 ml/10 g)诱导小鼠急性肝损伤模型,观察HY-12对小鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平的影响以及对肝匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平的影响;肝组织HE染色;免疫组化SP法观察肝组织中CYP2E1的表达;Western blot法检测小鼠肝脏CYP2E1的蛋白表达水平;qRT-PCR法检测小鼠肝脏CYP2E1 mRNA表达水平。结果 HY-12各剂量组可降低急性肝损伤小鼠血清中ALT、AST活性,降低肝匀浆MDA的水平,升高SOD、GSH-Px的水平,抑制了肝细胞中的CYP2E1的表达,明显减轻了小鼠肝组织病变程度。结论 HY-12对小鼠急性肝损伤具有一定的保护作用,其机制与抗机体脂质过氧化、抑制CYP2E1表达有关。Objective To study the protective effects of the inhibiting of HY-12 to CYP2E1 on CC14 induced acute liver injury in mice. Methods All 70 kunming mice were randomly divided into control group, model group, HY-day, the mice were injected with 0. 2% CC14（0. 1 ml/10 g） to induce mouse model of acute liver injury except the- normal group. To observe the level of liver homogenate about serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, and the influence of the malondialdehyde （MDA）, superoxide dismutase （SOD）, gluta- thione peroxidase （GSH-px） level;liver tissue has been stained by HE. The expression of CYP2E1 in liver tissue was measured by immunohistochemistry and Western blot. The expression level of CYP2E1 mRNA in the mice liver was detected by qRT-PCR. Results HY-12 could decrease ALT,AST activity in mice serum of the acute liver in- jury, reducethe level of MDA in liver homogenate, increase SOD and GSH-px levels, inhibit the CYP2E1 level in liver cells, and significantly reduce the degree of liver tissue lesions in mice. Conclusion HY-12 has certain pro- tective effect on acute liver injury in mice and its mechanism may be related to the body lipid peroxidated and in- hibited CYP2E1 expression.

关 键 词：5′-硝基乙酰化橙皮苷 急性肝损伤 四氯化碳 CYP2E1 

分 类 号：R966[医药卫生—药理学] R282.71[医药卫生—药学]