Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice

The prevalence of obesity-associated conditions raises new challenges in clinical medication. Although altered expression of drug-metabolizing enzymes (DMEs) has been shown in obesity, the impacts of obese levels (overweight, obesity, and severe obesity) on the expression of DMEs have not been elucidated. Especially, limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children. Here, a high-fat diet (HFD) and three feeding durations were used to mimic different obese levels in C57BL/6 mice. The hepatic expression of five nuclear receptors (NRs) and nine DMEs was examined. In general, a trend of induced expression of NRs and DMEs (except for and ) was observed in HFD groups compared to low-fat diet (LFD) groups. Differential effects of HFD on the hepatic expression of DMEs were found in adult mice at different obese levels. Family-based dietary style of an HFD altered the ontogenic expression of DMEs in the offspring older than 15 days. Furthermore, obese levels of parental mice affected the hepatic expression of DMEs in offspring. Overall, the results indicate that obese levels affected expression of the DMEs in adult individuals and that of their children. Drug dosage might need to be optimized based on the obese levels.

Reactivation of visual cortical plasticity by caloric restriction mediated by AMPK-SIRT1 pathway from monocular deprivation in adult mice / 中华实验眼科杂志

Objective This study was to investigate the effect of caloric restriction on the plasticity of visual cortex in adult monocular deprivation (MD) amblyopic mice,as well as to promote the treatment of amblyopia,and to explore the possible molecular mechanism of this benefical effect.Methods Fifty healthy newborn Kunming mice of clean grade were randomly divided into 3 groups using a random number table method:normal control group (n =14),MD+ ad libitum group (n=18) and MD+ caloric restriction group (n=18).A mouse model of adult MD amblyopia was established,and caloric restriction intervention and ad libitum were performed on MD + caloric restriction group and MD+ ad libitum group,respectively.The visual acuity and flash visual evoked potential (F-VEP) of each group were detected.The synaptic structure of visual cortex neurons was observed by transmission electron microscope,and the expression of phosphorylated AMP-activated protein kinase-α(p-AMPKα) and silent information regulator 1 (SIRT1) in visual cortex were detected by Western blot.The animal feeding and use was in accordance with the standards set by the ARVO.Results The weight of mice in MD+ caloric restriction group increased from the beginning of the first week,and was significantly lower than that in the MD + ad libitum group (P＜0.05).Compared with the MD+ ad libitum group,the visual acuity was restored,the latency was shortened,and the amplitude of F-VEP was increased in the deprived eyes of MD+ caloric restriction group (all at P＜0.05).Transmission electron microscope observation showed that the width of synaptic gap of visual cortical neurons was significantly narrower,and the thickness of postsynaptic density was significantly thicker in MD+ caloric restriction group than that in the MD+ ad libitum group (both at P＜0.05);compared with the normal control group,the synaptic gap was widened and the postsynaptic density was significantly thicker than that in the MD+ ad libitum group (both at P＜0.05).Western blot showed that the expression of p-AMPKα in visual cortex in the normal control group,MD+ caloric restriction group and MD+ ad libitum group was 0.89±0.03,0.94±0.02 and 0.74 ±0.02,and the expression of SIRT1 was 0.97±0.11,0.95±0.14 and 0.58±0.13,respectively,showing significant differences among the three groups (F =14.57,P =0.00;F=23.91,P=0.00),the expressions of p-AMPKα and SIRT1 in visual cortex were increased in MD+ caloric restriction group than those in M D+ ad libitum group (both at P＜0.05).Conclusions Caloric restriction can restore the ultrastructure of synapses and improve the visual cortical plasticity in adult MD mice,so that help to improve visual function.Its mechanism may be related to the activation of AMPK-SIRT1 pathway.

A Study on the Endoplasmic Reticulum Stress-induced Cardiac Hypertrophy in Adult APPswe/PS1dE9 Transgenic Mice / 现代生物医学进展

Objective:The present study was designed to explore the role of ER stress in cardiac hypertrophy of adult APPswe /PS1dE9 transgenic mice.Methods:10 adult APPswe/PS1dE9 transgenic mice and 10 C57BL/6 wild type (WT) mice were divided into the transgenic experimental and control group,WT experimental and control group,respectively,with 5 mice in each group.Experimental groups received a low dose ofIsoproterenol (ISO) (2 mg/kg) once a day for 4 weeks to induce cardiac hypertrophy,while control groups received the same volume of normal saline.After 4 weeks,the mice were anesthetized,followed by,electrocardiogram (ECG) recording and the measurement of the heart rate and body weight before being sacrificed.The heart was dissected out,and the masses of heart and the left ventricle were measured,the left ventricule mass index (LVW/BW) and the whole heart weight ratio (HW/BW) were calculated.HE staining was used to observe the pathological and morphological changes of cardiomyocytes,and Western Blot and immunohistochemistry were used to detect the expressions of ER stress relevant proteins-GRP78,JNK,P-JNK and CaMKII.Results:Compared with WT experimental mice,the ventricular wall in the APPswe/PS1dE9 transgenic experimental mice was apparently hypertrophic after the induction by low doses of ISO,and the HW/BW and the LVW/BW were also significantly increased in the APPswe/PS1dE9 transgenic experimental mice than those in the transgenic control mice,WT experimental and control mice (P＜0.05).HE staining showed that compared with the transgenic control mice,WT experimental and WT control mice,in the adult APPswe/PS1dE9 transgenic experimental mice,the cardiomyocyte diameter was obviously increased,cell density was decreased,the capillary density was decreased,the intercellular substance was increased,and the intercellular space was increased.Western blot showed that the expression of GRP78,p-JNK and CaMKII in the experimental group of adult APPswe / PS1dE9 transgenic mice were significantly higher than those in the transgenic control mice and WT mice (P＜0.05,P＜0.01).There were no significant difference among the control group oftransgenic mice and the two groups of WT mice.Immunohistochemistry showed that the positive rates of GRP78 and CaMKII in the cytoplasm of cardiomyocytes of the APPswe/PS1 dE9 transgenic experimental mice were significantly higher than those of experimental WT mice (80％&40 ％)(P＜0.05),and the expressions in the two control groups were negative.The positive rates of p-JNK and JNK in the APPswe/PS1dE9 transgenic experimental mice were 90％ and 40％ respectively,and the expressions were negative in other three groups.Conclusions:The adult APPswe/PSldE9 transgenic mice are more prone to cardiac hypertrophy than WT mice after the induction with a low dose of ISO.ER stress is involved in the formation of cardiac hypertrophy in adult APPswe/PS1dE9 transgenic mice.

Acteoside promotes proliferation of neural stem cells from adult mice by activating PI3 K/AKT pathway / 中国药理学通报

Aim Toclarifytheeffectofacteosideon proliferation of neural stem cells (NSCs ) from adult mice,as well as the involved signaling pathway.Meth-ods NSCswereisolatedfromthesubventricularzone (SVZ)of adult C57BL/6 mice,then identified by im-munofluorescence staining with Nestin,the marker of NSCs.NSCs were exposed to acteoside (5,10,20,40μmol·L-1 )in absence of mitogen(EGF/bFGF)for 24 h.We employed CCK8 assay to detect NSCs viability and BrdU staining to identify NSCs proliferation.We performed Western blot to quantify the expression level ofp-AktinducedbyacteosideonNSCs.Results With-out mitogen,acteoside increased NSCs proliferation by activating p-Akt,which can be blocked by LY294002, the inhibitor of PI3K/AKT signaling pathway.Conclu-sion ActeosidepromotestheproliferationofNSCsfrom adult mice by activating PI3K/AKT pathway.

Acrolein-induced cell apoptosis in adult mice cardiomyocytes / 中国生化药物杂志

Purpose To investigate the responsiveness of intracellular oxygen free radical and calcium on acrolein exposure and acrolein-induced cardiomyocytes apoptosis. Methods The viable adult mice cardiac myocytes were isolated by modified langendorff methods. We have examined the intracellular oxygen free radical and calcium concentration using DCF and Fura-2 AM, and the cardiomyocytes viability with WST assay. Are evaluated the DNA ladder pattern and cell apoptotic morphology on the adult mice cardiomyocytes that are exposed to acrolein. Results Our results show that acrolein can increase markedly the intracellular oxygen free radical and calcium concentration, that reach 12 fold and twofold respectively compared to the resting value when the cells were exposed to 1 μmol/L of acrolein. Moreover, the injury induced by acrolein in cardiac myocytes is concentration-dependent. The cardiomyocytes viability treated with 25, 50, 100 μmol/L of acrolein respectively were significantly lower compared to controls (P ＜ 0.01 ). DNA ladder pattern and apoptotic morphological changes were found after being exposed to acrolein in the adult mice cardiomyocytes. Conclusion It is concluded that acrolein induces adult mice cardiomyocytes apoptosis, and it may be due to the increased intracellular oxygen free radicals and calcium concentration.

The Analysis of Mouse Blood Serum and Colture of Primary Hepatocytes Induced by Phenobarbital Sodiu / 医学研究杂志

Objective To investigate the biological characteritics of adult animal hepatocytes induced by phenobarbital sodium(PBS) in vivo,and to study the potential value of biological artificial liver of effective hepatocytes.Methods 12 adult male mice,are yandomly divided in to preinducing group and controll group.The preinducing group are intraperitoneally injected PBS per day,45mg/kg for 7 times in total;the controll ware injected NS.after that,we detected the blood serum TP,BUN,CHOL,HDLC.And the same amount of isolative hepatocytes was developed after being developed 48h;MTT was used to investigate the proliferation of hepatocytes after being developed 24h;chromosome was investigated to observe the cell division;and the survival deadline and morphology was also investigated.Results The TP had remarkable difference between the two groups(t=2.678,P