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| 1 | Nrf2抗氧化损伤通路在CCl_4所致小鼠肝毒性中的保护作用(英文)显示文摘目的观察核转录相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)抗氧化损伤通路对四氯化碳(CCl4)所致小鼠肝毒性的保护作用。方法选取Nrf2-null、Wild-type、Keap1-KD、Keap1-HKO小鼠,按基因型分为4组,分别给予40 mg/kg CCl4腹腔注射,腹腔注射生理盐水(10 m L/kg)作对照,16 h后收集血浆和肝组织样本,检测血中谷丙转氨酶(alanine transaminase,ALT)和乳酸脱氢酶(lactic dehydrogenase,LDH)活性以及肝组织中丙二醛(malondialdehyde,MDA)含量;HE染色观察肝组织病理学变化,Real-time PCR和Western blot法检测相关基因表达。结果 CCl4增加Nrf2-null组和Wild-type组血中ALT、LDH活性及肝组织MDA含量,同时造成肝组织病理损伤,而在Keap1-KD组和Keap1-HKO组影响不明显;Nrf2因子靶基因(Nqo1和Gclc)在CCl4的诱导表达逐渐增高(顺序为Nrf2-null、Wild-type、Keap1-KD、Keap1-HKO),继而使炎症因子、内质网应激基因、细胞凋亡基因、细胞坏死基因的表达(m KC、MIP-2、IL-1β、TNFα、Gadd45、Chop10、Bax、Caspase 3、Mcl、Noxa)按Nrf2-null、Wild-type、Keap1-KD、Keap1-HKO顺序逐渐下降。结论 Nrf2因子激活保护CCl4所致小鼠肝损伤反应。 | 陆远富 Connie Wu 刘杰 Curtis Dean Klaassen | 2015 | 遵义医学院学报2015，38，1： | 11 |
| 2 | 齐墩果醇酸对化学物质致小鼠急性肝损伤的保肝作用(英文)显示文摘目的:评价齐墩果醇酸(OA)对急性肝损伤的保肝作用.方法:小鼠sc OA 200 μmol·kg^(-1)三天,然后给予肝毒物.通过病理组织学观察及测定血清丙氨酸转氨酶和艾杜糖醇脱氢酶活性来估价肝损伤.结果:OA能明显减轻四氯化碳,溴苯,醋氨酚,速尿,硫代乙酰胺,鬼笔毒环肽,秋水仙硷,氯化镉,D—半乳糖胺和内毒素等所致小鼠急性坏死性肝损伤,降低这些肝毒物所引起的血清转氨酶和艾杜糖醇脱氢酶的升高,但对氯仿,二甲亚硝氨,鹅膏菌索和烯丙醇的毒性无作用.结论:OA能减轻多种化学物质(但并非全部)引起的肝损伤.其保肝机制可能是多方面的. | 刘杰 刘亚平 Curtis D KLAASSEN | 1995 | 中国药理学报1995，16，2： | 5 |
| 3 | Regulation of hepatic micro RNA expression by hepatocyte nuclear factor 4 alpha显示文摘AIM To uncover the role of hepatocyte nuclear factor 4 alpha(HNF4α) in regulating hepatic expression of micro RNAs.METHODS Microarray and real-time PCR were used to determine hepatic expression of micro RNAs in young-adult mice lacking Hnf4α expression in liver(Hnf4α-Liv KO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-Ⅱ, and histone modifications to loci of micro RNAs in mouse liver and human hepatoma cells. Dual-luciferase reporter assay was conducted to determine effects of HNF4α on the promoters of mouse and human micro RNAs as well as effects of micro RNAs on the untranslated regions(3'UTR) of two genes in human hepatoma cells. RESULTS Microarray data indicated that most micro RNAs remained unaltered by Hnf4α deficiency in Hnf4α-Liv KO mice. However, certain liver-predominant micro RNAs were down-regulated similarly in young-adult male and female Hnf4α-Liv KO mice. The down-regulation of mi R-101, mi R-192, mi R-193 a, mi R-194, mi R-215, mi R-802, and mi R-122 as well as induction of mi R-34 and mi R-29 in male Hnf4α-Liv KO mice were confirmed by real-timePCR. Analysis of public chromatin immunoprecipitationsequencing data indicates that HNF4α directly binds to the promoters of mi R-101, mi R-122, mi R-194-2/mi R-192 and mi R-193, which is associated with histone marks of active transcription. Luciferase reporter assay showed that HNF4α markedly activated the promoters of mouse and human mi R-101b/mi R-101-2 and the mi R-194/mi R-192 cluster. Additionally, mi R-192 and mi R-194 significantly decreased activities of luciferase reporters for the 3'UTR of histone H3F3 and chromodomain helicase DNA binding protein 1(CHD1), respectively, suggesting that mi R-192 and mi R-194 might be important in chromosome remodeling through directly targeting H3F3 and CHD1.CONCLUSION HNF4α is essential for hepatic basal expression of a group of liver-enriched micro RNAs, including mi R-101, mi R-192, mi R-193 a, mi R-194 and mi R-802, through which HNF4α may play a major role in the post-transcriptional regulation of gene expression and maintenance of the epigenome in liver. | Hong Lu Xiaohong Lei Jerry Liu Curtis Klaassen | 2017 | World Journal of Hepatology2017，9，4： | 3 |
| 4 | Nephrotoxicity of CdCl2 and Cdmetallothionein in cultured rat kidney proximal tubules and LLC-PK1 cells显示文摘 | Liu J Liu Y Klaassen CD | 1994 | Toxicol Appl Pharmacol1994，128，： | 2 |
| 5 | Cadmium absorption and its relationship to divalent metal transporter-l in the pregnant rat显示文摘 | Leazer TM Liu Y Klaassen CD | 2002 | Toxicol Appl Pharmacol2002，185，： | 2 |
| 6 | Vertebral spinal osteophytes 显示文摘 | Klaassen Z Tubbs RS Apaydin N | 2011 | Anat Sci Int2011，86，1： | 1 |
| 7 | Mental health of Dutch peacekeping veterans 10-25 years after deployment 显示文摘 | Klaassens ER van Veen T We~rts JM | 2008 | Eur Psychiatry2008，23，7： | 1 |
| 8 | Crystal structureof an ACh-binding protein reveals the ligandbinding domain ofnicotinic receptors显示文摘 | Brejc K van Dijk W J Klaassen R V | 2001 | Nature2001，411，： | 1 |
| 9 | Economics of sustainability or the sustainability of economics: different paradigms显示文摘 | Ger A J Klaassen Johannes B Opschoor | 1991 | Ecological Economics1991，4，： | 1 |
| 10 | Cadmium-induced apoptosis in mouse liver显示文摘 | Habeebu SS Liu J Klaassen CD | 1998 | Toxicol Appl Pharmacol1998，149，： | 1 |
| 11 | Metallothionein protection of cad- mium toxicity 显示文摘 | Klaassen C D Liu J Diwan B A | 2009 | Toxicology and Applied Pharmacology2009，238，3： | 1 |
| 12 | Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice 显示文摘 | Pacyniak E Hagenbuch B Klaassen CD | 2011 | Toxicol Appl Phammcol2011，257，1： | 1 |
| 13 | Metallothionein :An intracellular protein to protect against cadmiumtoxicity 显示文摘 | Klaassen C D Liu J Choudhuri S | 1999 | Annual Review of Pharmacology andToxicology1999，39，： | 1 |
| 14 | Metallothionein:an in- tracellular protein to protect against cadmium toxicity显示文摘 | Klaassen C D Liu J Choudhuri S | 1999 | Annual Review of Pharmacology and Toxicology1999，39，1： | 1 |
| 15 | Antenatal oligohydramnios of renal origin: long-term outcome显示文摘 | Klaassen I Neuhaus TJ Mueller-Wiefel DE | 2007 | Nephrol Dial Transplant2007，22，2： | 1 |
| 16 | Metaproteomics approach to study the functionality of the microbiota in the human infant gastrointestinal tract显示文摘 | Klaassens ES de Vos WM Vaughan EE | 2007 | Appl Environ Microbiol2007，73，： | 1 |
| 17 | The rotating island pedicle flap: an aesthetic and functional imp rnvement on the subcutaneous island pediele flap显示文摘 | Salmon PJM Klaassen MF | 2004 | Dermatol Surg2004，30，： | 1 |
| 18 | Vertebral spinal osteophytes显示文摘 | Klaassen Z Tubbs RS Apaydin N | | 0，，01： | 1 |
| 19 | An explicit surface- potential-based MOSFET model for circuit simulation 显示文摘 | Van Langevelde R Klaassen F M | 2000 | Solid-State Electronics2000，44，3： | 1 |
| 20 | Regulation of mRNA expression of xenobiotic transporters by the pregnane X receptor in mouse liver,kidney,and intestine显示文摘 | Cheng X Klaassen CD | 2006 | Drug Metab Dispos2006，34，11： | 1 |
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