Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.

Effect of Cholesterol Content in Diet on Atorvastatin(ATO)-induced Liver Injury in Golden Hamsters

[Objectives]The objective of this study was to investigate the effect of cholesterol content in high-fat diet on atorvastatin(ATO)-induced liver injury in golden hamsters and compare the degree of liver injury caused by two high-fat diets with different cholesterol proportions.[Methods]Male golden hamsters were randomly and evenly divided into different groups and given different high-fat diets for 14 consecutive days by gavage to establish hyperlipidemia models.From the 15th d on,the hamsters in the model groups were given ATO at a dose of 5 mg/kg,one a day,for 9 consecutive days.Blood was sampled from the orbital veins of the hamsters for the determination of biochemical indicators.Liver tissues of the hamsters were sampled,paraffin-embedded,sliced,stained by HE(hematoxylin-eosin)method and observed under an optical microscope.[Results]Compared with standard diet group,the body weight increased significantly(P<0.05),the serum TC,TG and LDL-C levels increased significantly(P<0.05),the serum HDL-C level declined significantly(P<0.05),and the ALT and AST levels increased significantly(P<0.05)in the high-fat diet groups.This trend was more obvious in the high-fat II group than the high-fat I group.After ATO intervention,the HDL-C,TBIL and TBA levels increased significantly(P<0.05),and the liver ALT and AST levels further increased(P<0.05)in the model groups.This trend was more obvious in the model II group than the model I group.The morphological inspection shows that the fat deposition in the liver tissues was severe;the hepatocytes in the model groups were obviously damaged;the liver injury in the hamsters fed high-fat diet containing 0.2%cholesterol and intervened with ATO was relatively mild but severer than the high-fat diet groups.[Conclusions]Hamster models of hyperlipidemia were successfully established in this study.High-fat diet could cause liver injury.While lowering blood lipid level,ATO aggravated liver injury.Among the high-fat diets with different proportions of cholesterol,the diet containing 0.2%cholesterol had little effect on ATO-induced liver injury.

Vomeronasal organ lesion disrupts social odor recognition, behaviors and fitness in golden hamsters

Most studies support the viewpoint that the vomeronasal organ has a profound effect on conspecific odor recog­nition,scent marking and mating behavior in the golden hamster(Mesocricetus auratus).However,the role of the vomeronasal organ in social odor recognition,social interaction and fitness is not well understood.There­fore,we conducted a series of behavioral and physiological tests to examine the referred points in golden ham­ster.We found that male hamsters with vomeronasal organ lesion showed no preference between a predator odor(the anal gland secretion of the Siberian weasels(Mustela sibirica)and putative female pheromone components(myristic acid and palmitic acid),but were still able to discriminate between these 2 kinds of odors.In behavior­al tests of anxiety,we found that vomeronasal organ removal causes female hamsters to spend much less time in center grids and to cross fewer center grids and males to make fewer crossings between light and dark boxes than sham-operated controls.This indicates that a chronic vomeronasal organ lesion induced anxious responses in females.In aggressive behavioral tests,we found that a chronic vomeronasal organ lesion decreased agonistic behavior in female hamsters but not in males.The pup growth and litter size show no differences between the 2 groups.All together,our data suggested that vomeronasal organ ablation disrupted the olfactory recognition of social chemosignals in males,and induced anxiety-like and aggressive behavior changes in females.However,a vomeronasal organ lesion did not affect the reproductive capacity and fitness of hamsters.Our studies may have important implications concerning the role of the vomeronasal organ in golden hamsters and also in rodents.

Characterization of SHARPIN knockout Syrian hamsters developed using CRISPR/Cas9 system

Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to establish a novel geneticallyengineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system.Methods : A single- guide ribonucleic acid targeting exon 1 of SHARPIN gene was designedand constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatalmutants were identified by genotyping. SHARPIN protein expression was detectedusing Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymicweights were measured, and organ coefficients were calculated. Histopathologicalexamination of the spleen, liver, lung, small intestine, and esophagus was performedindependently by a pathologist. The expression of lymphocytic markers and cytokineswas evaluated using reverse transcriptase- quantitative polymerase chain reaction.Results : All the offspring harbored germline- transmitted SHARPIN mutations.Compared with wild- type hamsters, SHARPIN protein was undetectable in SHARPIN −/−hamsters. Spleen enlargement and splenic coefficient elevation were spotted inSHARPIN −/− hamsters, with the descent of MLNs and thymuses. Further, eosinophilinfiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagiwere obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless,the expression of CCR3, CCL11, Il4 , and Il13 was upregulated in the esophagi. Theexpression of NF- κB and phosphorylation of NF- κB and IκB protein significantly diminishedin SHARPIN −/− animals.Conclusions : A novel SHARPIN KO hamster was successfully established using theCRISPR/Cas9 system. Abnormal development of secondary lymphoid organs andeosinophil infiltration in multiple organs reveal its potential in delineating SHARPINfunction and chronic inflammation.

Role of the Chinese Herbal Medicine Xianhuayin on the Reversal of Premalignant Mucosal Lesions in the Golden Hamster Buccal Pouch

Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene （DMBA）-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Methodology The animals were randomly divided into a non-diseased control group （n=5） and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA （0.5% in acetone） to generate an oral mucosa premalignant lesion. Animals in the experi- mental group were further divided into Xianhuayin-treated group （n=30）, untreated prem＇alignant lesion group （n=10） and normal saline （NS）-treated group （n=10）. The cheek （buccal） pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. Results In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic （SEM） analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated- group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic micro- scopic （TEM） analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin. Conclusion Xianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

Postnatal development of NADPH-diaphorase expression in the visual cortex of the golden hamster

Nitric oxide is an important neuromodulator in the brain and is involved in the development of visual system. But it is not clear how nitric oxide and nitric oxide synthase （NOS） are involved in the developing visual cortex of rodents. Thus we examined the expression of NOS activity in the postnatal developing visual cortex of the golden hamster by using histochemical technique for NADPH-diaphorase （NADPH-d）. A heavily stained NADPH-d band was observed in the neuropil of the visual cortex. This NADPH-d band initially appeared in the cortical plate from the day of birth （P0） to postnatal day 4 （P4）. From P7 to P21, this band was confined to area 17 and migrated to the deeper layers Ill IV and V VI before it eventually disappeared at P28. Such developmental trends of the band correlated well with the process of formation and establishment of the geniculo-cortical projection patterns. Thus, the areal specific development of the band suggests that NOS is closely related to the cortical differentiation and synaptic formation of the primary visual cortex. On the other hand, monocular eye enucleation on P1 could not alter the appearance of this NADPH-d positive band, indicating a non-activity dependant role of NOS. In addition, differences in the laminar distributions and developmental sequence between the heavily and lightly stained NADPH-d positive neurons during development suggest that they play different roles in the development.

FURTHER STUDIES ON THE MALIGNANT TRANSFORMATION OF SYRIAN GOLDEN HAMSTER EMBRYO CELLS IN VITR0 BY THORIUM DIOXIDE AND RARE EARTH IRON MINERAL DUSTS

Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final concentration of 17.0,

Genetically-engineered hamster models: applications and perspective in dyslipidemia and atherosclerosis-related cardiovascular disease

Cardiovascular disease is the leading cause of morbidity and mortality in both developed and developing countries,in which atherosclerosis triggered by dyslipidemia is the major pathological basis.Over the past 40 years,small rodent animals,such as mice,have been widely used for understanding of human atherosclerosis-related cardiovascular disease(ASCVD)with the advantages of low cost and ease of maintenance and manipulation.However,based on the concept of precision medicine and high demand of translational research,the applications of mouse models for human ASCVD study would be limited due to the natural differences in metabolic features between mice and humans even though they are still the most powerful tools in this research field,indicating that other species with biological similarity to humans need to be considered for studying ASCVD in future.With the development and breakthrough of novel gene editing technology,Syrian golden hamster,a small rodent animal replicating the metabolic characteristics of humans,has been genetically modified,suggesting that gene-targeted hamster models will provide new insights into the precision medicine and translational research of ASCVD.The purpose of this review was to summarize the genetically-modified hamster models with dyslipidemia to date,and their potential applications and perspective for ASCVD.