Preliminary exploration of animal models of congenital choledochal cysts

BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical groups.Serum levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.

The bio-active components of the Mongolian medicine Horcha-6 and therapeutic mechanism in the rat migraine model

Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.

Experimental models of high-risk bowel anastomosis in rats:A systematic review

BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles

Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combining FUS and microbubbles(μBs),and edaravone was used to verify whether the free radical scavenger had a protective effect on the model.The brain tissue of each group was sectioned to observe the gross histology,blood-brain barrier(BBB)permeability,cerebral infarction volume,and histopathological changes.Results:Compared with the FUS group,the BBB permeability was significantly increased in the FUS+μBs(F&B)group(p=0.0021).The second coronal slice in the F&B group had an obvious hemorrhage lesion,and the FUS+μBs+edaravone(F&B&E)group had smaller hemorrhage areas;however,ICH did not occur in the FUS group.The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group(p=0.0030)and F&B&E group(p=0.0208).HE staining results showed that nerve fibrinolysis,neuronal necrosis,microglia production,and erythrocytes were found in both the F&B group and the F&B&E group,but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.Conclusions:A rat ICH model was successfully prepared using theμBs assisted FUS treatment,and edaravone had a therapeutic effect on this model.This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.

Establishment of extensively drug-resistant Pseudomonas aeruginosa pneumonia model in rat

Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,medium bacterial group,and high bacterial group.The low,medium and high bacterial groups were given intratracheal instillation of 0.1 mL of bacterial suspension(bacterial concentration in turn is 7.5×10^(9),3×10^(10),6×10^(10)CFU/mL),while the blank group were given the same volume of sterile normal saline.After modeling,the general conditions of rats in each group were observed,including mental state,hair,respiration,activity,eating,weight,and the survival curve was drawn.The pathological characteristics of lung tissue and the infiltration of inflammatory cells were observed.Pathogenic identification of each group was carried out by bacterial culture of lung tissue homogenate.Results:The general state of the blank group was normal,and the rats in other groups showed signs of mental depression,bristling,shortness of breath,even oral and nasal bleeding,decreased food intake and activity,and significant weight loss,and different degrees of death within 48 hours,the difference was statistically significant(P<0.05).Pathological results showed that the alveolar structure of rats in the blank group was complete,and the alveolar space was clear without exudation.The lung tissue of the low and medium bacterial groups showed obvious inflammatory cell infiltration,alveolar structure destruction,alveolar septum thickening,interstitial edema,but the pathological damage of the medium group was more severe,with a mortality rate of up to 50%,and the mortality rate of the low bacterial group was 17%.In the high bacterial group,red blood cells,inflammatory cells and a large amount of fibrin-like exudation can be seen in the alveolar space,which has the pathological characteristics of acute respiratory failure,and the mortality rate is as high as 67%.The results of bacterial culture of lung tissue homogenate showed that the blank group had no bacterial colonies,while PA colony growth can be seen in low,medium and high bacterial groups.Conclusion:9 Intratracheal instillation of low bacterial count(0.1 mL of 7.5×10^(9) CFU/mL)XDR-PA bacterial suspension can successfully construct a rat pneumonia model of XDR-PA infection.

A comparative study of two methods for establishing a chronic non‑bacterial prostatitis model in rats‑

Objective:To compare the biological characteristics and stability of the chronic non-bacterial prostatitis(CNP)model in rats induced by the depot combined with estrogen induction method and the autoimmune response induction method.Methods:The CNP rat model was prepared using the depot combined with 17β-estradiol induction method in the depot hormone group and three concentrations of prostate protein homogenate at 40 mg/mL,20 mg/mL and 10 mg/mL in the autoimmune group,respectively.The degree of prostate tissue damage was evaluated by pathology(HE staining),and the immunoturbidimetric method was used to evaluate the contents of immunoglobulins IgA,IgM and IgG.ELISA was used to evaluate interleukin-1β(IL-1β),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and high-sensitivity-C-reactive protein(hs-CRP),and electrochemiluminescence was used to evaluate the expression level of testosterone(T),and the two model methods were compared.Results:Compared with the sham-operated group,the body mass of rats in both models was significantly lower in the depot hormone group and autoimmune group before extraction(P<0.01,P<0.01),and histopathology of the prostate in both models showed destruction of glandular structure and a significant increase in inflammatory cells.Compared with the depot hormone group and the autoimmune group,the histopathological changes and inflammatory pathological scores of prostate and the contents of immune indexes IgA,IgM and IgG were significantly different in the depot hormone group(P<0.05,P<0.05,P<0.05),and the levels of IL-1β,IL-10,TNF-α,hs-CRP and T were significantly changed in the autoimmune group(P<0.01).The comparison between the high,medium and low dose groups of the autoimmune group,in which the pathological changes in the medium dose of the autoimmune group were slightly better than the other two groups between the groups,but the changes in IL-1β,IL-10,TNF-α,hs-CRP,and T in the low dose of the autoimmune group were the most significant(P<0.05).Conclusion:The pathological tissues of the chronic non-bacterial prostatitis model established by the depot combined with estrogen induction method and the autoimmune response induction method both showed significant changes,and the comprehensive indexes indicated that the depot combined with estrogen induction method was a more appropriate modeling choice.

Mechanism of AiTongXiao granule in the treatment of hepatocellular carcinoma based on network pharmacology and rat transplanted liver cancer model

Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets,and databases including Gene Cards,OMIM,Drugbank and TTD were further used to collect HCC-related drug targets.The intersecting targets were obtained by mapping the drug and disease targets.The component-targets network was constructed and visualized by Cytoscape 3.8.2 software.Protein-protein interaction(PPI)network was built by STRING online platform,and the topological relationship and core targets was analyzed and screened by using CytoNCA software.In addition,Metascape database was used to perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.At last,rat liver transplanted liver cancer model was established by using Walker-256 cell line and treated by AiTongXiao granule for 15 days.Western blot was used to further compare the expression levels of AKT,pAKT,p53,p-p53,ERK1/2 and ERK1/2 in the tumor between treatment group and the control group.Results:257 active components were obtained from AiTongXiao granule,corresponding to 294 drug targets.Meanwhile,233 of the 7993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets.11 core targets including AKT1,IL6,TP53,MAPK3,TNF,JUN,CASP3,MAPK1,MYC,PTGS2,MMP9 were further obtained by median screening.GO and KEGG analysis results showed that these core targets enriched to HBV,TNF and cancer related pathways.The rat transplanted liver cancer model results indicated significant down regulation for AKT,p-AKT,pERK1/2,and significant up regulation of p-p53 after AiTongXiao granule treatment(P<0.05).Conclusion:AiTongXiao granule could act to multiple cancer related pathways,and AKT,p53 and ERK1/2 were validated to be regulated by ATXF in rat model.The mechanism may be through the regulation of the above signaling pathways to exert anti-liver cancer effect.

Motivational and Methodological Factors Involved in the Helping Behavior Test in Laboratory Rodents

Empathy allows humans and other animals to share the emotional state of another, adopting that individual’s perspective on a given situation. This ability is fundamental for species living in groups. Helping behavior in laboratory animals has been used to study empathy. In this test, subjects are exposed to a conspecific that is trapped and learn to open the cage to release the other animal. However, the interpretation of helping behavior as an emphatically motivated action is still controversial. Here we review the studies that use the helping behavioral test proposed by Ben-Ami Bartal and colleagues in 2011 to better understand motivational factors for this behavior. In addition, we compare methodological aspects of these studies. In conclusion, helping behavior can be driven by empathy, but other factors such as the desire for social contact and learning components cannot be ruled out as motivators. In addition, studies focused on evaluating neurobiological mechanisms underlying helping behavior in laboratory rodents can help elucidate the factors involved in releasing the trapped co-specific.

A Model of Focal Cortical Infarctionin Rat:Mini mally Invasive Craniotomy

目的建立一种稳定的大鼠脑局灶性梗死模型,以用于脑梗死后神经干细胞移植的长期观察。方法37只大鼠随机分为实验组和对照组。微创法经颞骨局部钻孔开颅,采用直接结扎大脑中动脉终段,同时永久结扎同侧颈总动脉、暂时性夹闭对侧颈总动脉的方法制备大鼠脑梗死模型。通过大鼠脑梗死后的神经功能评分、墨汁灌注、TTC染色、MRI成像结果对该模型进行评价。结果大鼠术后状态良好,实验组大鼠观察4周后死亡率低为6 .25 %。大鼠神经功能评分均为1分,墨汁灌注及TTC染色观察梗死范围局限于皮层,4周后MRI成像测量梗死体积稳定,平均为83 .52 mm3。结论该模型对大鼠创伤小,梗死灶的位置和体积恒定,长期存活率高,为脑梗死后神经干细胞移植的研究提供了一种理想的动物模型。

Improved Method for Pancreaticoduodenal Transplantation in Rat Model

Objective: To improve the method of pancreaticoduodenal transplantation and to establish a more physiological rat model. Methods: SD rats served as donors and recipients. The vein was reconstructed by end-to-side anastomosis between the donor portal vein and the recipient superior mesenteric vein, and arterial reconstruction was carried out by end-to-side anastomosis of the donor to the recipient abdominal aorta. Enteric drainage was performed by side-to-side anastomosis between the duodenum of donors and that of recipients. Results: Fifty experiments were performed. The successful rate of transplantation which restored the recipients euglycemia were 78%. Conclusion: This model of pancreaticoduodenal transplantation in rats was stable and reliable, which was in accordance with the trend of clinical pancreas transplantation and could be applied for further scientific research.

A chronic ulcerative colitis model in rats

INTRODUCTIONIn recent years,there have been many reports aboutanimal model to investigate drugs for inflammatorybowel diseases (IBD).The experimental animalmodel often used is acetic acid-induced damage ofcolonic muscosa.In the present study,this animalmodel was investigated by administering variousconcentrations of TNBS.

Study of heteroserum-induced rat liver fibrosis model and its mechanism

AIM To investigate the morphological changes in the process of heteroserum induced rat liver fibrosis and the mechanism of fibrogenesis of this model. METHODS A model of heteroserum induced rat liver fibrosis was established by intraperitoneal injection of porcine serum. In addition to the observation of the morphological changes of this model, the infiltration of eosinophils and mast cells were measured quantitatively and the deposition of IgG and complement C 3 was detected by immunofluorescence. RESULTS The rat liver fibrosis was induced successfully at the end of the 8th week after the injection of heteroserum. Besides the increase of hepatic stellate cells (HSC) during the process of liver fibrosis, proliferation and activation of primary mesenchyma cells (PMCs) were also found. In the early stage, the infiltration of eosinophils and mast cells was significantly increased and the deposition of IgG and complement C 3 was positive in the portal tracts and septa, while gradually reduced after the injection was stopped. CONCLUSIONS This model is suitable for the research on liver fibrogenesis; the pathogenesis of this model may be related with the allergen induced late phase reaction (LPR) caused by the injection of heteroserum, and the HSCs and the PMCs are important sources of ECM producing cells.

Modeling postpartum depression in rats： theoretic and methodological issues

The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.

Establishing an experimental rat model of photo-dynamically-induced retinal vein occlusion using erythrosin B

AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.

A modified rat model for hepatocellular carcinoma

BACKGROUND: Rat hepatocellular carcinoma ( HCC ) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-cancer treat- ments ( drug, hepatectomy and liver transplantation ), and designing cancer prevention strategies. In this study we es- tablished a modified rat model of hepatocellular carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats were fed with diethylnitrosamine (DENA) by three methods for evaluation of general condi- tions for 130 days: Doppler ultrasonographic measurement, laparotomy and histopathological examination. RESULTS: No rat died in control group ( group A) and modified DENA-induction-HCC group ( group C), but 6 deaths in classical DENA-induction-HCC group (group B) (survival rate 80%). All survived rats in groups B and C de- veloped diffusive hepatocellular carcinoma and liver cirrho- sis. General appearance of rats in the group C was better than that in the group B. CONCLUSION: With good general conditions for surgery, the modified rat model for hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.

Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis

AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.

Potential rat model of anxiety-like gastric hypersensitivity induced by sequential stress

AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.

Experimental models of non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.

Preparation method of an ideal model of multiple organ injury of rat with severe acute pancreatitis

AIM： To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis （SAP）.METHODS： SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 （ET-1）, nitrogen monoxidum （NO）, phospholipase A2 （PLA2）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） in plasma were determined. The histological changes of multiple organs were observed under light microscope.RESULTS： The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 （1.10）, 2.58 （0.70）, 2.54 （0.71） vs 0.20 （0.04）, 0.30 （0.30）, 0.22 （0.10） at 3, 6 and 12 h in ascites/body weight ratio; 1582 （284）, 1769 （362）, 1618 （302） （U/L） vs 5303 （1373）, 6276 （1029）, 7538 （2934） （U/L） at 3, 6 and 12 h in Amylase; 0.016 （0.005）, 0.016 （0.010）, 0.014 （0.015） （EU/mL） vs 0,053 （0.029）, 0.059 （0.037）, 0.060 （0.022） （EU/mL） at 3, 6 and 12 h in Endotoxin; 3.900 （3.200）, 4.000 （1.700）, 5.300 （3.000） （ng/L） vs 41.438 （37.721）, 92.151 （23.119）, 65.016 （26.806） （ng/L） at 3, 6 and 12 h in TNF-α, all P 〈 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, ileum, lymphonode, thymus, myocardium and brain.CONCLUSION： This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAR