The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.
Acetylcholine ; Animals ; Aorta ; Endothelium ; Gene Expression Profiling ; Genetic Background ; Mice ; Mice, Inbred Strains ; Transcriptional Activation ; Vasodilation

C57BL/6N is the most widely used inbred mouse strain applied in a wide variety of research areas including cancer, cardiovascular biology, developmental biology, diabetes and obesity, genetics, immunology, neurobiology, and sensorineural research. To compare the fertilization rates of C57BL/6NKorl mice with two commercial C57BL/6N stocks, differences in reproductive organ structures, sperm and egg numbers, fertilization rates, and embryo development rates among C57BL/6NKorl (Korea FDA source), C57BL/6NA (USA source), and C57BL/6NB (Japan source) mice were determined. Among the stocks, no significant differences were detected in organ weight and histological structure of male and female reproductive organs, although body weight was higher in C57BL/6NKorl mice than that in the other groups. The concentration and morphology of sperm and eggs in C57BL/6NKorl mice were similar to those of C57BL/6NA and C57BL/6NB mice. Furthermore, the three stocks had similar in vitro fertilization and embryo development rates, although these rates tended to be higher in C57BL/6NB mice. Pup body weight was higher in C57BL/6NKorl and C57BL/6NB mice than that in C57BL/6NA mice. The results of the present study suggest that C57BL/6NKorl, C57BL/6NA, and C57BL/6NB mice obtained from three different sources have similar fertilization and embryo development rates, although there were slight differences in the magnitude of their responses rates.
Allergy and Immunology ; Animals ; Biology ; Body Weight ; Developmental Biology ; Eggs ; Embryonic Development ; Female ; Fertilization in Vitro ; Fertilization* ; Genetics ; Humans ; Male ; Mice* ; Mice, Inbred Strains ; Neurobiology ; Obesity ; Organ Size ; Ovum ; Pregnancy ; Spermatozoa

Animals ; Antibodies, Monoclonal ; immunology ; Cell Line ; Cercopithecus aethiops ; Cricetinae ; Culicidae ; Dengue Virus ; immunology ; Encephalitis Virus, Japanese ; immunology ; Encephalitis, Japanese ; immunology ; Mice ; Mice, Inbred Strains ; Vero Cells ; Viral Vaccines ; immunology

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.
Acetic Acid ; Acute Lung Injury ; chemically induced ; drug therapy ; pathology ; Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Carrageenan ; administration & dosage ; Chlorogenic Acid ; pharmacology ; Dinoprostone ; antagonists & inhibitors ; biosynthesis ; Disease Models, Animal ; Dosage Forms ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Ear ; pathology ; Edema ; chemically induced ; drug therapy ; pathology ; Flavonoids ; pharmacology ; Lipopolysaccharides ; administration & dosage ; Male ; Mice ; Mice, Inbred Strains ; Pain ; chemically induced ; drug therapy ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Xylenes ; administration & dosage

Brown algae are well known as a source of biologically active compounds, especially those having antioxidant activities, such as phlorotannins. In this study we examined the antioxidant activities of crude phlorotannins extracts (CPEs) obtained from Sargassum hemiphyllum (SH) and fractionated according to the molecular weights. When CPEs were administrated at a dose of 30 mg/kg to Kunming mice pre-treated with carbon tetrachloride (CCl4), the levels of oxidative stress indicators in the liver, kidney and brain were significantly reduced in vivo. All the components of various molecular weight fractions of CPEs exhibited greater scavenging capacities in clearing hydroxyl free radical and superoxide anion than the positive controls gallic acid, vitamin C and vitamin E. Particularly, the components greater than 30 kD obtained from ethyl acetate phase showed the highest antioxidant capacities. These results indicated that SH is a potential source for extracting phlorotannins, the algal antioxidant compounds.
Animals ; Antioxidants ; isolation & purification ; pharmacology ; Ascorbic Acid ; pharmacology ; Brain ; drug effects ; metabolism ; pathology ; Carbon Tetrachloride ; antagonists & inhibitors ; toxicity ; Carbon Tetrachloride Poisoning ; drug therapy ; metabolism ; pathology ; Chemical Fractionation ; methods ; Gallic Acid ; pharmacology ; Hydroxyl Radical ; antagonists & inhibitors ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Liquid-Liquid Extraction ; methods ; Liver ; drug effects ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Phaeophyta ; chemistry ; Sargassum ; chemistry ; Superoxides ; antagonists & inhibitors ; metabolism ; Tannins ; isolation & purification ; pharmacology ; Vitamin E ; pharmacology

OBJECTIVETo investigate the effect of CCM3 gene defection on lead induced cell genotoxicity in mouse embryonic fibroblasts.

METHODSC57 female mice were mated with CCM3 gene heterozygous male mice. E13.5 embryos were taken to isolate primary mouse embryonic fibroblasts. After genotyping, wild type and heterozygous cells were treated with different doses of lead acetate. Cell viability, genotoxicity and protein expression were detected by MTS assay, CB micronucleus method and Western blot, respectively.

RESULTSMouse embryonic fibroblasts with lead acetate treatment for 24 h, wild-type cells 100.00 µmol/L lead acetate-treated group (69.16±1.36) and the control group (100.00±2.33) compared to cells decreased by 30%, CCM3 heterozygous type cell 100.00 µmol/L lead acetate-treated group (87.16±5.50) and the control group (100.00±2.06) compared to cells decreased by 13%, the difference was statistically significant (F values were 98.59, 82.63, P<0.001). Lead acetate treatment after 48 h, wild-type cells 100.00 µmol/L lead acetate-treated group (51.99±5.62) and the control group (100.00±3.11) compared to cells decreased by 50%, heterozygous type cells 100.00 µmol/L lead acetate treatment group (66.33±4.06) and the control group (100.00±5.72) compared to cells decreased by 35%, the differences were statistically significant (F values were 82.63, 36.86, P < 0.001). The results of CBMN test showed that with increased dose, micronucleus cell rate of two genotypes showed an increasing trend, in the wild-type cells, the micronucleus cell rate (/1 000) for the control group, 29.6±2.2, 6.25 µmol/L dose group 47.3±6.6, 25 µmol/L dose group 55.5±9.1, 100.00 µmol/L dose group 66.8±3.5; heterozygous cells micronucleus cell rate (/1 000) for the control group, 35.3±5.6, 6.25 µmol/L dose of 50.0±8.3, 25.00 µmol/L dose group 57.0±8.5, 100.00 µmol/L dose group 58.8±2.1. Micronucleus cell rates (/1 000) were significant differences, in 100.00 µmol/L dose groups of two genotypes. Western blot results showed that wild-type cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.70±0.03) was 1.32 times higher than the control group (0.53±0.07), heterozygous cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.48±0.02) was 1.77 times higher than control group that of 0.27±0.04, there was statistically significant difference (F values were 14.77, 25.74, P < 0.001); wild-type cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.69±0.03) was 1.06 times higher than the control group (0.65±0.07), heterozygous cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.99±0.04) was 1.55 times higher than the control group CCM3 expression levels (0.64±0.06), there was statistically significant difference (wild-type cells: F = 7.08, P = 0.012, heterozygous type cell: F = 13.49, P = 0.002).

CONCLUSIONCCM3 gene may play a role in lead-induced genetic toxicity of mouse embryonic fibroblasts, CCM3 gene-lead interactions effects on mouse embryonic fibroblasts cell toxicity.

Animals ; Apoptosis Regulatory Proteins ; DNA Damage ; Embryo, Mammalian ; Female ; Fibroblasts ; Genotype ; Male ; Membrane Proteins ; Mice ; Mice, Inbred Strains ; Micronuclei, Chromosome-Defective ; Organometallic Compounds ; Proto-Oncogene Proteins

OBJECTIVETo investigate the effect of γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l -alanyl]-S-phenylglycine t-butyl ester, DAPT) on hyperoxia-induced brain white matter injury in mice.

MWTHODSThree-day-old C57BL/10J mouse pups were divided into air control (C) group, control+DAPT (10 mg/kg, injected intraperitoneally) group, hyperoxia group (exposed to 80% oxygen for 48 h), and hyperoxia+DAPT group. The brain and body weights of the mice were measured at postnatal days 3, 5, 12, and 28. Real-time PCR was used to detect Notch intracellular domain (NICD) mRNA expression in the brain after modeling, and the expressions of NG2 and myelin basic protein (MBP) were detected by double-labeled immunofluorescence assay to verify the oligdendrocycle type at postnatal day 12. The mice in each group were bred until postnatal day 28 for Morris water maze test.

RESULTSThe brain and body weights were significantly decreased in mice in hyperoxia group compared to the control mice, but increased significantly after DAPT treatment (P<0.05). Real-time PCR showed that a 48-hour hyperoxia exposure significantly increased NICD mRNA expression in the brain (P<0.05), which was decreased by co-treatment by DAPT (P<0.05). Hyperoxia also resulted in enhanced NG2 expression and lowered MBP expression in the brain (P<0.05). Compared with the control mice, the mice exposed to hyperoxia showed prolonged escape latency (P<0.05) and spent less time in the target quadrant with a lowered number of passing through the virtual platform (P<0.05). All these parameters were significantly improved by co-treatment with DAPT.

CONCLUSIONSpecific inhibition of Notch signaling pathway activation in the brain by the γ-secretase inhibitor DAPT can ameliorate white matter injury and learning and memory impairment in newborn mice with hyperoxia exposure.

Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Animals ; Body Weight ; Brain ; metabolism ; pathology ; Dipeptides ; pharmacology ; Hyperoxia ; physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Organ Size ; Receptors, Notch ; metabolism ; Signal Transduction ; White Matter ; pathology

OBJECTIVETo study the protective effect of baicalin solid dispersion (BSD) on D-galactosamine (D-GalN) induced acute hepatic injury in mice, and to compare it with baicalin alone.

METHODSSixty mice were randomly divided into six groups, i.e., the normal control group, the D-GalN model group, the bifendate group (at the daily dose of 200 mg/kg), the baicalin group (at the daily dose of 50 mg/kg), the low dose BSD group (at the daily dose of 50 mg/kg), and the high dose BSD group (at the daily dose of 100 mg/kg), 10 in each group. 0.5% CMC-Na at 20 mL/kg was administered to mice in the normal group and the model group by gastrogavage, while corresponding medication was administered to mice in the other three groups by gastrogavage. Seven days after administration, acute hepatic injury model was induced by intraperitoneal injection of D-GalN. The liver index and the spleen index were calculated. The serum activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST), the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver homogenate were measured. The pathological changes of the liver tissue were observed by HE staining.

RESULTSCompared with the normal control group, widespread inflammation and necrosis was significant in the liver tissue of the D-GalN model group; the liver index, serum ALT and AST levels and hepatic MDA content obviously increased, hepatic SOD activity decreased, showing statistical difference (P < 0.05). Compared with the model group, the liver index, the serum levels of ALT and AST, and hepatic MDA decreased, hepatic SOD increased, the degree of hepatic tissue injury was significantly improved in the low dose and high dose BSD groups. Besides, better effects were obtained in the low dose BSD group than in the baicalin group with statistical difference (P < 0.05).

CONCLUSIONBSD could significantly protect D-GalN induced acute hepatic injury of mice, and its effect was superior to that of baicalin alone.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; blood ; drug therapy ; Flavonoids ; therapeutic use ; Galactosamine ; adverse effects ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred Strains ; Protective Agents ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVETo search for an optimal activation protocol by comparing the chemical activation effects of single-activator and combined activation protocols on mouse oocytes following injection of round spermatids (ROSI) from spermatogenic cells cultured in vitro.

METHODSUsing different concentrations of ethanol, ionomycin (Ion), calcium ionophore A23187 (CIA), strontium chloride (SrCl2), cycloheximide (CHX), and 6-dimethylaminopurine (6-DMAP) , we activated post-ROSI oocytes for different times, and activated them by combined protocols at optimal concentrations and action times according to different activation channels. We compared the activation effects of single-activator and combined activation protocols by comparing the rates of fertilization, cleavages, and morulas and blastocysts.

RESULTSWith a single activator, the optimal protocols of different activators were as follows: 7% ethanol for 6 min, 5 micromol/L CIA for 5 min, 5 micromol/L Ion for 5 min, 2 mmol/L 6-DMAP for 2 h, 10 mmol/L SrCl2 for 1.5 h, and 10 microg/ml CHX for 1.5 h, among which 10 mmol/L SrCl2 for 1.5 h achieved the highest rate of morulas and blastocysts, significantly better than CHX (P < 0.05) but with no remarkable difference from other activators. The ethanol + 6-DMAP group showed a significantly higher rate of morulas and blastocysts (29.63%) than all other combined activation groups and single-activator groups except SrCl2 (P < 0.05), and it also exhibited higher rates of normal fertilization, cleavages and morula than the SrCl2 group, but with no significant difference.

CONCLUSIONThe single-activator 10 mmol/L SrCl2 for 1.5 h and the combined activation of 7% ethanol for 6 min + 2 mmol/L 6-DMAP for 2 h are the optimal protocols for chemical activation of mouse oocytes following ROSI, and the combined activation of ethanol + 6-DMAP is even superior to the single-activator protocol.

Animals ; Cycloheximide ; pharmacology ; Female ; Fertilization in Vitro ; Ionomycin ; pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Oocytes ; cytology ; drug effects ; Spermatids ; cytology ; drug effects

OBJECTIVETo investigate the effect of Xiaoyao Powder (XP) and its compatible prescriptions on the ethology, morphology, and activities of neurotransmitters, thus exploring their effects and mechanism in preventing and treating D-galactose induced Alzheimer's disease (AD) model mice, and clarifying the compatibility mechanism for soothing Gan, nourishing blood, and invigorating Pi.

METHODSSixty SPF mice were randomly divided into the blank control group, the model group, and the XP group, Shugan Jianpi group (SJ), Shugan Yangxue group (SY), and Jianpi Yangxue group (JY), 10 in each group.The AD mouse model was prepared by peritoneal injecting D-galactose. Meanwhile, mice in the blank control group and the model group were administered with physiological saline (at the daily dose of 24 mL/kg) by gastrogavage. Mice in the XP group (2.485 g/kg), the SY group (1.136 g/kg), the SJ group (1.775 g/kg), and the JY group (2.059 g/kg) were administered with corresponding medicated decoction by gastrogavage, with the gastric volume of 24 mL/kg. On the 41st day the training of capability for learning and memory was started. On the 42nd day capability for learning and memory was tested. The brain tissue was cut. One half was used to determine the contents of homogenate acetyl cholinesterase (AchE), choline acetyltransferase (ChAT), and monoamine oxidase (MAO).Another half was used to carry out morphological observations.

RESULTSThe capability for learning and memory could be improved and the latency time could be lowered in all the treatment groups. Besides, the homogenate AchE and MAO could also be elevated, ChAT could be lowered; the morphology, number, and distribution of neurons could be improved. But the improvement of ethology, morphology, and activities of neurotransmitters were most obviously seen in the XP group.

CONCLUSIONSXP could improve the ethology, morphology, and activities of neurotransmitters, and showed better effects on prevention and treatment of AD. The rationality of compatibility methods and combination thinking ways of soothing Gan, nourishing blood, and invigorating Pi were clarified.

Alzheimer Disease ; metabolism ; psychology ; Animals ; Behavior, Animal ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Male ; Mice ; Mice, Inbred Strains ; Neurotransmitter Agents ; metabolism