内源性中叶素可减轻血管紧张素Ⅱ诱导的乳鼠心肌细胞肥大

目的研究内源性中叶素(IMD)与心肌细胞肥大间的相互作用关系。方法血管紧张素Ⅱ(AngⅡ)孵育乳鼠心肌细胞构建心肌肥大模型。应用Western blot及放射免疫法测定心肌细胞IMD产生和分泌,实时定量PCR(Real-timePCR)方法检测心肌细胞IMD及其受体系统降钙素受体样受体/受体活性修饰蛋白(CRLR/RAMPs)基因表达的变化。并以[3H]-亮氨酸([3H]-Leu)摄入及脑钠素(BNP)基因表达作为心肌细胞肥大的指标。结果 AngⅡ孵育下调心肌细胞IMD生成、表达,并影响其受体系统的基因表达。反过来,利用IMD抗体及其受体阻断剂阻断内源性IMD的生物学效应可增强AngⅡ诱导的心肌细胞肥大反应。结论内源性IMD及其受体系统参与了心肌肥大的发生、发展,对其生成、表达的干预有可能成为今后防治心肌细胞肥大的新途径。     

酸敏感离子通道-1a在急性肺损伤大鼠肺组织中的表达及作用初探

目的探讨酸敏感离子通道-1a(ASIC1a)在急性肺损伤(acute lung injury,ALI)大鼠肺组织中的表达及可能的作用。方法 SPF级♂SD大鼠32只,随机分为正常组、ALI组、阿米洛利组和阳性药物组。对动脉血进行血气分析,观察肺组织病理学,肺组织称重后计算湿干重比,ELISA检测血清中TNF-α的表达,q PCR和Western blot检测肺组织中ASIC1a的表达。结果与正常组相比,模型组肺组织损伤明显;肺组织湿干重比明显升高; TNF-α的表达水平明显升高(P <0. 01)。阿米洛利组及阳性药物组肺组织损伤明显减轻;肺组织湿干重比较模型组明显下降,TNF-α的表达水平明显降低(P <0. 01)。免疫组化、q PCR和Western blot结果显示,与正常组相比,模型组ASIC1a的表达量明显升高(P <0. 01),阿米洛利组与模型组相比,ASIC1a的表达量明显减少(P <0. 01)。结论在脂多糖诱导的ALI大鼠肺组织中ASIC1a的表达增加,其可能参与ALI的发生、发展。     

RIP140/PGC-1α在AngⅡ调节心肌能量代谢中的作用研究

目的探讨转录辅助因子受体相互作用蛋白140(receptor interacting protein 140,RIP140)与过氧化物酶体增殖物受体γ共激活因子1α(peroxisome proliferator-activated receptor gamma coactivator-1α,PGC-1α)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)调节心肌细胞能量代谢中的作用。方法借助腺病毒载体系统诱导RIP140和PGC-1α基因过表达;利用荧光检测系统测定乳鼠心肌细胞线粒体ATP的含量;实时荧光定量PCR和Western blot的方法检测RIP140和PGC-1α的表达情况。结果乳鼠心肌细胞给予100 nmol·L-1AngⅡ刺激36 h后,心肌细胞线粒体ATP的含量降低(P<0.01),同时伴随RIP140 mRNA与蛋白水平的升高,而PGC-1αmRNA与蛋白水平下调。AngⅡ诱导的ATP含量减少在过表达RIP140组中进一步下降,而在过表达PGC-1α组中有所减轻。结论AngⅡ诱导的ATP含量减少与RIP140表达上调和PGC-1α表达下调有关。     

TREM-1在宫内感染新生大鼠的表达及意义

目的 探讨髓系细胞触发受体l(TREM-1)在宫内感染新生大鼠中的表达及其诊断价值.方法 30只SD孕鼠随机分为正常对照组(A组,6只)和宫内感染模型组(B组,24只),腹腔注射脂多糖0.5 mg/kg建立宫内感染模型,并分别于幼鼠出生后1、3、7、14d留取外周血及脑、肺组织.采用Western blot法和免疫荧光法检测脑组织和肺组织中TREM-1表达,ELISA法检测外周血TREM-1和TNF-α水平.结果 A组未见明显的TREM-1阳性染色细胞表达.与A组相比,B组新生大鼠脑组织、肺组织中TREM-1蛋白表达以及外周血中TREM 1、TNF-α水平在生后1d明显升高,3d达到峰值,14d逐渐降低.TREM-1和TNF-α表达水平呈正相关(r=0.794,P＜0.01).结论 宫内感染后,新生大鼠脑、肺组织及外周血中TREM-1表达明显升高,且与TNF α水平密切相关,有望成为早期诊断脓毒症的有用指标之一.     

肾脏花生四烯酸CYP羟化酶参与高血压的形成及维持正常血压的稳定

目的:研究肾脏特异性表达CYP4A1与血压变化的关系.方法:将含有开放阅读框的CYP4A1 cDNA克隆到真核表达载体pcDNA3.1,构建4Al/pcDNA3.1和反义4Al/pcDNA3.1重组体,舌下静脉注射转染SD雄性大鼠,经尾动脉测量收缩压.用Western blot及Northern blot分析转染对照pcDNA3.1质粒及正、反义CYP4A1重组体后,CYP4A1在大鼠的脑、心、肺、肝、肾组织表达水平.结果:转染正义、反义CYP4A1两周后,大鼠的血压与对照组相比分别增加1.8kPa±0.3kPa(13.2mmHg±2.5mmHg)和减少了1.7kPa±0.3kPa(13.0mmHg±2.2 mmHg).Western blot及Northern blot结果均显示CYP4A1可选择性地在肾脏表达,而在脑、心、肺、肝几乎无表达,且在给予反义CYP4A1的大鼠肾脏中CYP4Al蛋白表达几乎被完全阻断.结论:在正常的SD大鼠肾脏中,转染正、反义CYP4A1可引起血压升高和降低,说明肾脏花生四烯酸CYP羟化酶参与高血压的形成及维持正常血压的稳定.     

氨基酰化酶-1在肝癌组织中的表达及其临床意义

目的探究氨基酰化酶-1(ACY-1)在肝细胞癌(肝癌,HCC)组织中的表达及其临床意义。方法使用实时荧光定量PCR(qRT-PCR)技术对HCC患者的癌组织和相应癌旁组织中的ACY-1 mRNA表达进行检测;采用蛋白质印迹法(Western blot)检测肝癌和癌旁标本中ACY-1蛋白的表达,同时结合免疫组化的方法分析了ACY-1蛋白的表达与HCC的关系。结果 qRT-PCR和Western blot结果表明癌旁组织中ACY-1的mRNA和蛋白的表达高于肝癌组织。免疫组化结果与Western blot结果一致。另外,通过对ACY-1免疫组化结果与临床病理参数分析发现,ACY-1蛋白表达与AFP水平密切相关。结论 ACY-1可能与肝癌的发生发展密切相关。     

肝X受体对急性肺损伤保护机制的探讨

目的 探讨肝X受体对急性肺损伤的保护机制,观察凋亡抑制因子Api6、Caspase-3、Bcl-2的表达情况.方法 将54只雄性SD大鼠随机分为正常对照组(CL组)、内毒素处理组(LP组)、T0901317预处理组(TP组).TP组预处理后,脂多糖造模,于1h、4h、8h时处死大鼠采取肺组织,免疫组化染色测定凋亡因子Caspase-3、Bcl-2,蛋白定量检测Api6表达水平,同时测定动脉血气,观察电子显微镜下肺组织病理学改变.结果 与CL组相比,LP组动脉血氧分压均显著降低;病理形态学示:与LP组相比,TP组损伤明显减轻.通过Western blot检测肺Api6蛋白表达获知:TP组明显比LP组表达有所增加.结论 Api6在ALI大鼠肺组织中表达明显减少.Api6高表达对肺组织起到一定的保护作用.肝X受体激动剂预处理可以减轻脂多糖所致肺组织的损伤,其机制可能与其抑制促凋亡因子、增加抗凋亡因子表达有关.     

甘露消毒饮对手足口病模型乳鼠的干预效果及对TLR4/MAPKs/NF-κB信号通路影响

分析甘露消毒饮对手足口病(HFMD)模型乳鼠的干预效果及对TLR4/MAPKs/NF-κB信号通路影响。采用颅内接种EV71病毒建立18只HFMD乳鼠模型,随机分为模型组(n=6)、甘露消毒饮组(n=6)、TLR4信号通路抑制剂组(抑制剂组)(n=6),同时另取6只同龄健康乳鼠为正常组。甘露消毒饮组给予灌胃甘露消毒饮治疗(24.4 g/kg),抑制剂组给予腹腔注射TLR4抑制剂TAK-242(0.3 mg/kg),其余组给予生理盐水治疗,干预后12 h脱颈处死各组乳鼠,取腹主动脉血,并分离脑、骨骼肌、心脏、肺、小肠组织。HE染色观察病理组织,免疫荧光染色各组织EV71病毒抗原的表达。ELISA检测4组乳鼠血清MBP、LDH、CK、NSE、IL-6、IL-1β、IL-12、TNF-α含量,Western blot法检测各组乳鼠脑组织中TLR4/MAPKs/NF-κB信号通路相关蛋白的表达水平。HE染色和免疫荧光染色结果表明,正常组各组织正常,且各组织无EV71病毒抗原的表达。模型组乳鼠各组织中均观察到病理损伤和炎症反应,且各组织有EV71病毒抗原的表达。甘露消毒饮组和抑制剂组乳鼠各组织病...     

Dickkopf1在肝癌组织中的表达

目的 检测Diekkopf1(DKK1)在肝癌组织中的表达.方法 采用四种不同方法检测DKK1在肝癌组织和痛旁肝组织的表达.结果 半定量逆转录聚合酶链反应(RT-PCR)方法检测显示,DKK1在4/5肝癌中高表达;适时-PCR(Real-time PCR)方法检测显示,DKK1在8/14肝癌中高表达;Western blot方法检测显示,DKK1在2/4肝癌中高表达;免疫组化方法检测显示,DKK1在46/79肝癌中高表达,但与AFP表达水平、分化程度、TNM分期等临床病理特征无关.四种方法检测结果均显示DKK1在肝癌组织的表达显著高于癌旁肝组织.结论 DKK1在肝癌组织表达高于癌旁肝组织,可能与肝癌发生、发展相关.     

人肝细胞癌组织中叶酸受体和Delta样配体4的表达及分布

目的 探讨叶酸受体(FR)和Delta样配体4(Dll4)在人肝细胞癌(hepatocellular carcinoma,HCC)组织和正常肝组织中的表达及分布特点,评价其作为HCC治疗靶点的可行性。方法 收集2013年1—10月切除的24例HCC组织标本,收集同期9例肝血管瘤旁切除的正常肝组织。应用HE染色观察两组标本组织学结构;免疫组化、Western blot检测FR及Dll4的表达及分布情况。结果 免疫组化结果显示HCC组织中FR、Dll4阳性率均高于正常肝组织(P<0.05),Western blot检测HCC组织中FR和Dll4相对表达量均高于正常肝组织(P<0.05)。结论 FR和Dll4在HCC组织中高表达,可视为HCC基因治疗新的潜在靶点。     

CAR, the continuously advancing receptor, in drug metabolism and disease

The detoxification and elimination of potentially toxic foreign and endogenous compounds depends on the concerted action of xenobiotic metabolizing enzymes. Nuclear hormone receptors (NHRs) have emerged as key regulators of the expression of these enzymes and his review focuses on the xenosenor CAR (Constitutive Androstane Receptor, NR1I3). CAR is highly expressed in the liver and the small intestine, two key tissues expressing xenobiotic metabolizing enzymes, and mediates the induction of their expression by the widely used antiepileptic drug, phenobarbital (PB) and the potent synthetic inducer 1, 4-bis-(2-(3, 5, -dichloropyridyloxy)) benzene (TCPOBOP). TCPOBOP is an agonist ligand for CAR. PB induces its nuclear translocation, which results in increased expression of CAR target genes since, unlike the classical, ligand-dependent nuclear receptors, CAR is an apparently constitutive transactivator. This constitutive activity is inhibited by the inverse agonist ligands androstanol and androstenol. The CAR mediated induction of the expression of xenobiotic metabolizing enzymes is generally protective, but can be deleterious if toxic metabolites are produced. CAR also has a protective role in the stress response elicited by hyperbilirubinemia, as well as lithocholic acid induced cholestasis. In addition, recent studies show that CAR activation disrupts thyroid hormone homeostasis. Finally, CAR activation promotes hepatocyte proliferation and blocks apoptosis, and is essential for the tumorigenesis induced by its activators PB and TCPOBOP. The role of CAR in endobiotic and xenobiotics metabolism has clinical implications in disease prevention, drug-drug interactions, and the development of better drug treatments.     

Snail、E-cadherin 和N-cadherin 在非小细胞肺癌组织的表达及相关性研究

目的：探讨上皮型钙黏附素（E-cadherin）、神经型钙黏附素（N-cadherin）及Snail在非小细胞肺癌（NSCLC）中的表达及其临床意义。方法采用实时荧光定量PCR测定Snail、E-cadherin和N-cadherin基因在10对非小细胞肺癌及其癌旁正常肺组织中的表达情况,同时采用免疫组化法检测105例NSCLC以及41例癌旁组织中Snail、E-cadherin和N-cadherin蛋白的表达。结果与癌旁正常肺组织相比较,非小细胞肺癌组织中E-cadherin的表达显著减少,N-cadherin和Snail表达明显增加（P〈0.05）。NSCLC组织中,Snail的表达与N-cadherin的表达呈明显的正相关（P〈0.05,r=0.21）,与E-cadherin的表达呈显著负相关（P〈0.05,r=-0.39）,而N-cadherinl的表达与E-cadherin的表达也呈明显负相关（P〈0.05,r=-0.53）。结论非小细胞肺癌组织中, Snail、N-cadherin呈显著高表达,而E-cadherin呈显著低表达,三者可能通过相互作用共同参与NSCLC的发生和发展。     

The alpha 1C-adrenergic receptor: characterization of signal transduction pathways and mammalian tissue heterogeneity.

We recently reported the cloning of a novel alpha 1-adrenergic receptor (AR), the alpha 1CAR. By transient and stable expression of the alpha 1CAR and the previously cloned alpha 1BAR in COS-7 and HeLa cells, respectively, we have now compared their ability to interact with major signal-transduction pathways (including polyphosphoinositide hydrolysis, intracellular calcium, and cAMP metabolism), as well as their mammalian tissue localization. Both alpha 1C- and alpha 1BARs primarily couple to phospholipase C via a pertussis toxin-insensitive GTP-binding protein, leading to the release of calcium from intracellular stores. Even though alpha 1C- and alpha 1BARs activate polyphosphoinositide hydrolysis by similar biochemical mechanisms, the alpha 1CAR couples to phospholipase C more efficiently than does the alpha 1BAR; activation of the alpha 1CAR results in a 2-3-fold greater increase in inositol phosphates, compared with the alpha 1BAR. Both alpha 1AR subtypes can also increase intracellular cAMP, by a mechanism that does not involve direct activation of adenylyl cyclase. In agreement with ligand binding data, the agonist methoxamine and the antagonist WB4101 are 10-fold more potent in activating or inhibiting, respectively, the ability of the alpha 1CAR to stimulate phospholipase C, compared with the alpha 1BAR. In addition, methoxamine is almost a full agonist at the alpha 1CAR, whereas it can only weakly activate the alpha 1BAR. Tissue localization, using Northern blot analysis of total and poly(A)+-selected RNA from rabbit tissues, revealed striking mammalian species heterogeneity. As previously described, the alpha 1BAR is present in several rat tissues, including heart, liver, brain, kidney, lung, and spleen, whereas the alpha 1CAR is not present in any rat tissue studied. The alpha 1BAR is also present in rabbit aorta, heart, spleen, and kidney (and absent in rabbit liver), whereas the alpha 1CAR is present in rabbit liver. Our results indicate that the cloning and expression of different alpha 1AR subtypes represents a valuable tool to elucidate functional correlates of alpha 1AR heterogeneity.     

艾灸减轻新生小鼠缺氧缺血性脑病的作用及其机制研究

目的　研究艾灸减轻新生小鼠缺氧缺血性脑病（HIE）的作用及其机制。方法　55只出生7 d的ICR小鼠按照随机数字表法分为假手术组（Sham组）、模型组（HI组）和艾灸组（MOX组）。HI组和MOX组采用右侧颈总动脉结扎联合缺氧法制备HIE模型，MOX组建模后艾灸刺激大椎穴，35 min/次，1次/d，连续治疗3 d。处理结束后麻醉取脑，DAPI染色观察脑组织形态结构，TUNEL染色检测脑组织细胞凋亡；免疫荧光染色检测脑组织caspase-9表达；放射免疫分析法测定脑组织caspase-3含量。结果　与Sham组相比，HI组小鼠脑组织排列疏松，脑组织凋亡细胞数和caspase-9表达显著增多（P＜0.05）；与HI组相比，MOX组小鼠脑组织排列较致密，脑组织凋亡细胞数、caspase-9和caspase-3表达显著减少（P＜0.05）。结论　艾灸可能通过降低脑组织caspase-9和caspase-3的表达来减少细胞凋亡，从而减轻新生小鼠缺氧缺血性脑损伤。     

Effects of intrauterine undernutrition on the expression of CYP3A23/3A1, PXR,CAR and HNF4α in neonate rats

Cytochrome P‐450 3A (CYP3A) together with its nuclear receptors plays a critical role in drug metabolism. The present study investigated the effects of undernutrition in utero on hepatic mRNA and protein expression of the enzyme CYP3A23/3A1 and nuclear receptors including pregnane X receptor (PXR; NR1I2), constitutive androstane receptor (CAR; NR1I3) and nuclear factor‐4alpha (HNF4α; HNF4A) in neonatal rats. At gestational day 2, pregnant rats were randomly divided into two groups: nourished (fed ad libitum) and undernourished (50% of nourished group). The pups delivered by nourished rats were designated as the normal‐birth‐weight group (NBW, n=15) and those delivered by undernourished rats were designated as the low‐birth‐weight group (LBW, n=15). Hepatic mRNA expression was detected by quantitative real‐time PCR and the corresponding protein expression was examined by immunohistochemistry (IHC). Compared with NBW pups, LBW pups tended to have lower mRNA expression levels of CYP3A23/3A1, PXR and CAR but higher levels of HNF4α. Only the CAR mRNA expression differences were significant (p<0.05). mRNA expression of CYP3A23/3A1 correlated with that of HNF4α in both the LBW(r=0.808, p=0.007) and NBW (r=0.452, p=0.012) groups. CYP3A23/3A1 and CAR protein expression differed between the two groups (CYP3A23/3A1, χ²=7.87, p=0.005; CAR, χ²=12.069, p=0.001). In conclusion, these findings suggest that undernutrition may influence the mRNA expression of CAR and protein expression of both CYP3A23/3A1 and CAR in neonatal rats. Since CYP3A23/3A1 and CAR are critically involved in drug metabolism, these results may have clinical implications for optimal medication in LBW children. Copyright © 2008 John Wiley & Sons, Ltd.     

miR-552通过PTEN/AKT信号通路促进非小细胞肺癌A549细胞的恶性生物学行为

目的 探讨miR-552通过调控PTEN/AKT信号通路促进人非小细胞肺癌A549细胞的恶性生物学行为及其相关机制。方法 通过qRT-PCR检测人肺癌组织样本和人非小细胞肺癌A549细胞系中miR-552、PTEN mRNA的表达情况;通过Western blotting检测PTEN、AKT、p-AKT蛋白的表达情况;通过CCK-8检测miR-552表达对A549细胞增殖能力的影响;通过Transwell小室检测miR-552表达对A549细胞迁移和侵袭能力的影响;通过流式细胞术检测miR-552表达对A549细胞凋亡能力的影响。结果 miR-552在肺癌组织和A549细胞中的表达显著上调。过表达miR-552可显著促进A549细胞的增殖、迁移和侵袭,并抑制细胞凋亡,而抑制其表达则结果相反。与癌旁组织相比,肺癌组织中PTEN表达显著下调。过表达miR-552可下调PTEN蛋白表达,上调p-AKT蛋白表达,对AKT蛋白无影响,而抑制其表达则结果相反。结论 miR-552可能通过PTEN/AKT信号通路促进人非小细胞肺癌A549细胞的恶性生物学行为。     

黄连素激活Nrf2通路缓解新生大鼠哮喘模型氧化应激反应和对心肺组织的保护作用

目的：探讨黄连素（berberine,BB）对新生大鼠哮喘模型氧化应激反应的影响和对心肺组织的保护作用以及潜在的分子机制。方法：将新生SD雄性大鼠随机分成健康对照组、健康加药组、哮喘模型组和模型加药组;卵清蛋白诱导新生大鼠哮喘模型;收集肺泡灌洗液（broncho alveokar lavage fluid,BALF）并分析细胞类型和细胞数目;苏木伊红（hematoxylin eosin,HE）染色观察心肌组织和肺组织病理变化;末端标记法（terminal deoxynucleoitidyl transferase mediated nick end labeling,TUNEL）染色检测心肌组织和肺组织细胞凋亡情况;试剂盒检测血清中超氧化物歧化酶（superoxide dismutase,SOD）的活性和丙二醛（malondialdehyde,MDA）、一氧化氮（nitric oxide,NO）的含量;蛋白质印记检测肺组织中Kelch样ECH相关蛋白1（Kelch-like ECH-associated protein 1,Keap1）、NFE2相关因子2（NF-E2 related factor 2,Nrf2）和血红素氧合酶1（heme oxygenase 1,HMOX-1）的表达水平。结果：哮喘模型组与对照组相比,肺泡灌洗液中炎性细胞的数目显著增加;心肌组织细胞排列不规则,部分细胞结构不清晰;肺组织中有大量的炎性细胞浸润,黏膜下水肿,气道上皮断裂脱落,支气管壁明显增厚;心肌组织和肺组织中凋亡细胞比例显著增加;血清中SOD的活性显著降低,MDA和NO的含量显著增加;肺组织中Keap1、Nrf2和HMOX-1的表达水平显著升高。模型加药组与模型组相比,肺泡灌洗液中炎性细胞的数目明显减少;心肌组织较规则,细胞排列较整齐;肺组织中仍有部分炎性细胞浸润,部分肺泡壁增厚;心肌组织和肺组织中凋亡细胞比例显著降低;SOD的活性显著升高,MDA和NO的含量显著降低;Keap1、Nrf2和HMOX-1的表达水平显著升高。结论：黄连素可激活Nrf2通路,缓解新生大鼠哮喘模型的氧化应激反应,对心肺组织具有保护作用。     

Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor

The xenobiotic receptors, constitutive androstane receptor (CAR), and pregnane X receptor (PXR) regulate and alter the metabolism of xenobiotic substrates. Among the 19 functional UDP-glucuronosyltransferases (UGTs) in humans, UGT2B7 is involved in the metabolism of many structurally diverse xenobiotics and plays an important role in the clearance and detoxification of many therapeutic drugs. To examine whether this gene is regulated by CAR and PXR in vivo, transgenic mice expressing the entire UGT2B7 gene (TgUGT2B7) were created. Gene expression profiles revealed that UGT2B7 is differentially expressed in liver, kidney, adipocytes, brain, and estrogen-sensitive tissues, such as ovary and uterus. Liver UGT2B7 expression levels were decreased when TgUGT2B7 mice were treated with the CAR ligand 1,4-b-s-[2-(3,5,-dichloropyridyloxy)] (TCPOBOP) but not the PXR ligand pregnenolone 16α-carbonitrile. Although TCPOBOP decreased the levels of UGT2B7 mRNA in TgUGT2B7 mice, it had no affect on Tg(UGT2B7)Car(-/-) mice, adding support for a CAR-dependent mechanism contributing toward UGT2B7 gene suppression. Expression of promoter constructs in HepG2 cells showed the CAR-dependent inhibition was linked to hepatocyte nuclear factor-4α (HNF4α)-mediated transactivation of the UGT2B7 promoter. The inhibitory effect of CAR on UGT2B7 gene expression was validated in chromatin immunoprecipitation assays in which TCPOBOP treatment blocked HNF4α binding to the UGT2B7 promoter. These results suggest that HNF4α plays an important role in the constitutive expression of hepatic UGT2B7, and CAR acts as a negative regulator by interfering with HNF4α binding activity.     

Alterations in the distribution and orexigenic effects of dexamethasone in CAR-null mice

The constitutive androstane receptor (CAR, NR1I3) has emerged as an important regulator of drug metabolism. CAR responds to a wide spectrum of xenobiotics by inducing expression of cytochrome P450 (CYP) enzymes and a number of other proteins responsible for drug metabolism in the liver. The xenosensor function of CAR overlaps with that of the pregnane X receptor (PXR), another xenobiotic receptor that belongs to the nuclear hormone superfamily. We observed that injection of dexamethasone (Dex), a ligand for the glucocorticoid receptor (GR) and PXR but not CAR, results in an unexpected twofold increase in the stomach weight of CAR-null animals relative to wild-type animals. Here, we show that CAR knockout mice have elevated levels of Dex in the brain, resulting in a more rapid and robust increase in the hypothalamic expression of the GR-responsive target genes encoding neuropeptide Y (NPY) and neuropeptide Y receptor subtype 1 (NPY-R1). As expected, this is accompanied by a higher increase in the food intake of the CAR-null animals. The data described here highlight the complexity of the overlapping functions of CAR and PXR.