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制何首乌对大鼠肝脏P450酶5种亚型mRNA表达的影响
引用本文:黄春连,范雪梅,黎倩,王义明,王淑美,龚梦鹃,罗国安.制何首乌对大鼠肝脏P450酶5种亚型mRNA表达的影响[J].中国中药杂志,2017,42(2):352-356.
作者姓名:黄春连  范雪梅  黎倩  王义明  王淑美  龚梦鹃  罗国安
作者单位:广东药科大学 中药学院, 广东 广州 510006;清华大学 化学系, 北京 100084,清华大学 化学系, 北京 100084,广州康臣药业有限公司, 广东 广州 510610,清华大学 化学系, 北京 100084,广东药科大学 中药学院, 广东 广州 510006,广东药科大学 中药学院, 广东 广州 510006,广东药科大学 中药学院, 广东 广州 510006;清华大学 化学系, 北京 100084
基金项目:国家自然科学基金项目(81130066,81302731)
摘    要:考察制何首乌水提物作用后大鼠肝脏P450酶5种亚型的mRNA表达变化。SD大鼠随机分为正常对照组、制何首乌高、低剂量组(5.40,1.08 g·kg~(-1)),连续灌胃给药7 d。给药结束后,检测大鼠血清生化指标,并采用实时荧光定量PCR测定各实验组大鼠肝脏P450酶5种亚型mRNA表达。实验结果显示AST在高、低剂量组都显著下降;ALT在低剂量组显著降低,在高剂量组显著升高。高、低剂量组的大鼠肝组织P450酶5种亚型mRNA的表达均下调,且下调程度与给药剂量成一定的剂量性依赖。特别是高剂量制何首乌水提物能够显著抑制大鼠的CYP1A2和CYP2E1的mRNA表达。该研究发现大剂量制何首乌水提物具有肝毒性,且随着剂量增加其肝损伤程度增加。其中制何首乌水提物5.40 g·kg~(-1)对大鼠肝CYP1A2和CYP2 E1的mRNA的表达有明显抑制作用。

关 键 词:制何首乌水提物  肝损伤  P450酶  血清生化指标  mRNA表达
收稿时间:2016/10/11 0:00:00

Effect of processed Polygonum multiflorum on mRNA expression level of five subtypes of CYP450 enzymes in rat liver
HUANG Chun-lian,FAN Xue-mei,LI Qian,WANG Yi-ming,WANG Shu-mei,GONG Meng-juan and LUO Guo-an.Effect of processed Polygonum multiflorum on mRNA expression level of five subtypes of CYP450 enzymes in rat liver[J].China Journal of Chinese Materia Medica,2017,42(2):352-356.
Authors:HUANG Chun-lian  FAN Xue-mei  LI Qian  WANG Yi-ming  WANG Shu-mei  GONG Meng-juan and LUO Guo-an
Institution:School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China;Department of Chemistry, Tsinghua University, Beijing 100084, China,Department of Chemistry, Tsinghua University, Beijing 100084, China,Guangzhou Consun Pharmaceutical Co., Ltd., Guangzhou 510610, China,Department of Chemistry, Tsinghua University, Beijing 100084, China,School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China,School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China and School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China;Department of Chemistry, Tsinghua University, Beijing 100084, China
Abstract:To observe the effect of processed Polygonum multiflorum on mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. SD rats were randomly divided into the normal control group, processed P. multiflorum high dose and low dose groups (5.40 g·kg-1 and 1.08 g·kg-1). The rats in administration groups were continuously given with processed P. mutiflorum for 7 days by ig administration, and the rats in normal control group were given with the same volume of distilled water. After successive administration of 7 days, the serum biochemical indications were detected, and Real-time quantitative PCR technology was used to detect the mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. Experimental results showed that AST was decreased significantly in both low and high dose groups. ALT was significantly decreased in low dose group and significantly increased in high dose group. The mRNA expression levels of five subtypes of CYP450 enzymes in rat liver were decreased in high dose and low dose groups in a dose-dependent manner. Especially the high dose processed P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in rats. The study showed that high dose P. multiflorum water extract had hepatotoxicity, and the degree of liver damage was increased with the increase of dose. It shall be noted that 5.40 g·kg-1 water extract of P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in the liver of rats.
Keywords:processed Polygonum multiflorum  liver injury  CYP450  serum biochemical indicators  mRNA expression
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