Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet.

BACKGROUND: A long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. METHODS: Male Tibetan minipigs were fed either a normal diet or an HFC diet for 24 weeks. Thereafter, the minipigs were tested for physiological and biochemical blood indices, blood pressure, cardiac function, glucose tolerance, heart rate variability (HRV), and PPAR-associated gene and protein expression levels. RESULTS: HFC-fed minipigs exhibited IR through increased body weight, fasting blood glucose levels, plasma cholesterol and its composition, and insulin and free fatty acid (FFA) levels; decreased insulin sensitivity; impaired glucose tolerance; and hypertension. Increased C-reactive protein (CRP) levels, cardiac dysfunction, depressed HRV, and the up-regulation of PPAR expression in the abdominal aorta concomitant with down-regulation in the heart tissue were observed in HFC-fed minipigs. Furthermore, the levels of NF-κBp65, IL-1ß, TNF-α, MCP-1, VCAM-1, ICAM-1, MMP-9, and CRP proteins were also significantly increased. CONCLUSIONS: These data suggest that HFC-fed Tibetan minipigs develop IR and AS and that PPARs are involved in cardiovascular remodeling and impaired function.

Advances in Research on Pathological and Molecular Mechanism of Hyperuricemic Nephropathy Based on Animal Models / 实验动物与比较医学

Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.

Effects of 1 470 nm Semiconductor Laser on Vaporization Ablation, Cutting, and Coagulation in Ex Vivo Animal Tissue / 实验动物与比较医学

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting, coagulation, and thermal injury of ex vivo animal tissues, aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia.Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment, respectively. Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s. The effects of layers at powers of 60, 90, 120, 150, and 160 W on tissue injury were observed. Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury. Additionally, in coagulation mode, the effects of 30, 40, and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5, 10, and 15 seconds. Results When the optical fiber was placed 1 cm away from the tissue, the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue. However, at a distance of 0.5 cm, the 120 W, 150 W, or 160 W lasers caused slight damage to the bladder tissue. In addition, with the increase in output power, the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased, showing a good linear correlation between vaporization volume and total energy consumption (P<0.001). Histopathological HE staining results indicated that the coagulation layer thickness in the experimental group was 292.20-309.98 µm, and the vaporization layer depth was 1.49-4.52 mm. In the control group, the coagulation layer thickness was 289.91-303.53 µm, and the vaporization layer depth was 1.88-4.43 mm. There was no significant difference between the two groups (P>0.05). Moreover, when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2, the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power (P<0.05). The coagulated layer thickness in the experimental group was 496.04-514.47 µm, while that in the control group was 489.39-518.53 µm. Additionally, in coagulation mode, when ex vivo pig kidney tissue was irradiated for 5, 10, and 15 s with 30, 40, and 50 W semiconductor lasers, the coagulation diameter, groove depth, and coagulation efficiency gradually increased with the increase in laser output power (P<0.05). The coagulation layer thickness in the experimental group and control group was 399.10-449.98 µm and 392.97-447.65 µm, respectively, and the vaporization layer depth was 3.05-7.09 mm and 2.70-7.14 mm, respectively. There was no significant difference between the two groups (P>0.05).Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation, cutting, and coagulation effect on ex vivo tissues, with a good linear correlation between the effect and the output energy.

Expression and clinic significance of long non-coding RNA ZEB1-AS1 in breast cancer / 国际肿瘤学杂志

Objective To detect the expression and clinic significance of long non-coding RNA ZEB1-AS1 in breast cancer. Methods A total of 130 patients with breast cancer in Baoji Central Hospital of Shaanxi Province from June 2007 to April 2015 were selected. Quantitative real-time PCR(qRT-PCR)was used to detect the expression level of ZEB1-AS1 in breast cancer tissues and corresponding normal tissues,and the rela-tionships between the expression level of ZEB1-AS1 and the clinic characteristics of the patients and their overall survival time were analyzed. siRNA was used to disturb the expression of ZEB1-AS1. CCK-8 assay, clone formation assay and Transwell assay were used to detect the proliferation,cloning ability and migration of breast cancer MCF-7 cells in control group,siRNA-1 group and siRNA-2 group. Results The expression level of ZEB1-AS1 in breast cancer tissues was higher than that in corresponding normal tissues[M(QR ):0. 0016 (0. 0051)vs. 0. 0009(0. 0015);Z = - 4. 426,P < 0. 001]. The higher expression of ZEB1-AS1 was correlated with lymphatic metastasis(χ2 = 9. 148,P = 0. 027),negative human epidermal growth factor recep-tor 2(χ2 = 5. 039,P = 0. 025),triple negative breast cancer(χ2 = 4. 597,P = 0. 032). The patients with the higher expression of ZEB1-AS1 had a shorter overall survival time compared with the patients with the lower expression of ZEB1-AS1(χ2 = 14. 340,P < 0. 001). CCK-8 assay showed that knock down of ZEB1-AS1 after 72 h,the absorbance values of the control group,siRNA-1 group and siRNA-2 group were 0. 605 ± 0. 049, 0. 488 ± 0. 054,0. 417 ± 0. 038 respectively,with a statistically significant different( F = 15. 936,P <0. 001),and the two siRNA groups were significantly inhibited in cell proliferation compared with the control group(both P < 0. 05). The colonies of the control group,siRNA-1 group and siRNA-2 group were 297. 5 ± 11. 4,192. 0 ± 12. 1,204. 8 ± 12. 8 respectively,with a statistically significant different(F = 112. 526,P <0. 001),and the two siRNA groups were significantly inhibited in the cell clone compared with the control group(both P < 0. 001). The migratory cells numbers of the control group,siRNA-1 group and siRNA-2 group were 184. 5 ± 8. 6,147. 5 ± 18. 6,57. 6 ± 7. 3 respectively,with a statistically significant different( F =12. 409,P = 0. 001),and the two siRNA groups were significantly inhibited in the cell migration(both P <0. 001). Conclusion ZEB1-AS1 is overexpressed in breast cancer,overexpression of ZEB1-AS1 induces a shorter overall survival in breast cancer patients,and knock down of ZEB1-AS1 can inhibit the proliferation, migration and colony formation ability of the breast cancer cell line.

Application of non-invasive ventilator in acute heart failure with preserved ejection fraction / 中华急诊医学杂志

Objective To investigate the clinical features of patients with heart failure and the safety and efficacy of noninvasive ventilator in patients with heart failure.Methods Sequentially enrolled 65 patients who were diagnosed with decompensated heart failure in Tianjin Chest Hospital Heart Center from October 2016 to October 2017 and who had acute heart failure during hospitalization requiring noninvasive ventilator,were divided into the HF-PEF group (n=19) and HF-REF group (n=46).The clinical data of the two groups and the observation indexes before and after the application of the non-invasive ventilator were compared.Results Comparing the admission data of the two groups,the proportion of patients with hypertension (57.9％ vs 21.7％,P=0.005) and LVEF(％) (53.00±4.85 vs 33.07±7.24,P＜0.01)were significantly higher in the HF-PEF group than those in the HF-REF group;LVEDD (mm) in the HFPEF group was significantly lower than that in the HF-REF group (50.00±5.23 vs 63.82±8.95,P＜0.01).In the two groups of patients with acute left heart failure,blood lactate levels (mmol/L) in the HF-PEF group (4.20±1.06 vs 2.02±0.88,P＜0.05) and systolic blood pressure (mmHg) (151.32±43.40 vs 117.90± 19.55,P＜0.05) were significantly higher than those in the HF-REF group.After the application of non-invasive ventilator,systolic blood pressure (mmHg) (34.38±9.36 vs 16.94±5.19,P=0.038) and PaCO2 (mmHg)(2.49±0.98 vs-0.06±0.00,P=0.025),and lactic acid (mmol/L) (2.06±0.67 vs 0.04±0.01,P=0.001) were significantly lower in the HF-PEF group than those in the HF-REF group.While the NT-proBNP level (ng/L) (13 064.90±1 963.83 vs 11 687.13±1 028.03,P=0.848) did not decrease significantly,and the time of non-invasive ventilator application (h)was significantly longer than that in the HF-REF group (152.74±10.61 vs 71.03±10.41,P=0.013).Conclusions Hypertension is the main cause of HF-PEF group.The systolic blood pressure and blood lactate level in HF-PEF patients with acute left heart failure are significantly higher than HF-REF patients.Non-invasive ventilator is also safe and effective for the treatment of acute left heart failure in HF-PEF patients,but HF-PEF patients with acute left heart failure have a longer clinical remission time.

Brain histopathological changes in WHBE rabbits fed with high cholesterol diet plus copper drinking water / 中国实验动物学报

Objective To observe the pathological changes of brain tissues in the WHBE rabbit model of sporadic Alzheimer disease (AD). Methods Thirty 3 -4-month old male WHBE rabbits were randomly divided into 3 groups:normal control (NC) group, high cholesterol diet (HCD) group, high cholesterol diet + copper drinking water ( HCD+ Cu2+) group, 10 in each group. Another 10 senile (36-48-month old) male WHBE rabbits were taken as senile group. The NC group and the senile group were fed a normal basic diet, the HCD group fed a 2% cholesterol diet, and the HCD+Cu2+group fed a 2% cholesterol diet plus 0. 12 PPM copper drinking water for 12 weeks. The levels of total cholesterol (TC) and β-amyloid protein (Aβ) 1-42 were measured at 12 weeks. The activity of superoxide dismutase ( SOD) and the content of malondialdehyde (MDA) in the cortex and the hippocampus were detected. In addition, the covered area of Aβ, β-site APP cleaving enzyme 1(BACE1) and phosphorylated tau (p-tau) protein in coronal sections of brain tissues were also observed by immunohistochemical staining. The senile plaques and the neurofibrillary tangles were observed by Congo red and Bielschowsky staining, respectively. Results The body weight of WHBE rabbits in the senile group was significantly higher than that of the NC group ( P ＜ 0. 01 ), and the plasma TC and Aβ1 -42 in each group were significantly higher than that in the NC group (P ＜ 0.05, P ＜ 0.01). The activity of SOD in brain tissues was significantly lower than that of NC group (P＜ 0. 05), and the MDA content was significantly higher than that of NC group (P＜ 0. 05, P ＜ 0. 01). Immunohistochemical staining showed that the covered area of Aβ, BACE1 and p-tau in brain tissues of all groups were significantly higher than that of NC group (P ＜ 0. 05, P ＜ 0. 01), and the covered area of BACE1 and p-tau protein in the brain tissues of HCD + Cu2+group was also significantly higher than that of the HCD group (P ＜ 0. 05, P ＜ 0. 01). Congo red and Bielschowsky staining showed that the number of senile plaques and neurofibrillary tangles were observed in the brain tissues of the HCD, HCD+Cu2+and senile groups. Conclusions High cholesterol diet or supplemented with trace copper drinking water can induce obvious AD pathological changes in WHBE rabbit models of sporadic AD with obvious oxidative damage, increased Aβ deposition and senile plaque in the brain, and pathological changes of tau. WHBE rabbit can be used in the study of animal models of neurodegenerative diseases.

Comparison of pathological characteristics of Wistar and Lewis rat models of collagen-induced rheumatoid arthritis / 中国比较医学杂志

Objective To study the differences of symptoms and pathological features of Wistar and Lewis rat models of collagen-induced rheumatoid arthritis. Methods Wistar and Lewis rats were injected with intermixture of bovine TypeⅡ collage and complete Freund's adjuvant(CFA)for first immunization, then strengthen it after 14 days and observed the incidence of Wistar-RA group and Lewis-RA group. The degree of paws swelling and the titer of serum anti CII antibody were determined. The pathological changes in toe and joint tissues were examined at 12 weeks, and the expressions of VEGF, IL-6, IL-10 and IL-17A in the synovial membrane of ankle joint were detected. Results After collagen induction,the Wistar and Lewis rats showed paw swelling after 10 d and 14 d,and peaked at 21 d and 24 d,the titer of serum anti CII antibody was significantly increased at third week(P< 0.01), and arthritis index(AI)was also significantly increased(P< 0.01). In the Wistar-RA rat group, the rate of molding was 80%, and at fifth weeks, the swelling of the paws subsided and went into a flat level. The molding rate of the Lewis-RA group was 100%,at the seventh week,the swelling of paws subsided and went into a flat level. At 12 weeks,the two model groups showed severe articular cartilage erosion, synovial hyperplasia and inflammatory cell infiltration, neovascularization and pannus formation in the joint synovium,and the bone mineral density of the femur and tibia of the hind limbs was significantly decreased(P<0.01). The expression of VEGF,IL-6 and IL-17A in synovium was significantly increased(P< 0.05,P< 0.01). The expression of IL-10 was obviously decreased(P< 0.01). Compared with the Wistar-RA group,the paw volume and paw thickness were increased for a longer time in the Lewis-RA group,AI was higher than that of the Wistar-RA group,synovial angiogenesis and pannus formation were more distinct, the expression of VEGF in synovium was significantly higher than that of Wistar-RA group(P< 0.05), while the expression of IL-17A was significantly lower than that in the Wistar-RA group(P< 0.05). Conclusions Both the Wistar-RA rat model and Lewis-RA rat model show joint swelling,deformation and decreased activity. AI is increased,the expression of VEGF,IL-6 and IL-17A increased,and the expression of IL-10 decreased,which are consistent with the clinical manifestation. The Wistar-RA rat model has a short duration of swelling, while the Lewis-RA rat model has a longer swelling duration and more severe joint damages. The neovascularization and pannus formation are more obvious. The expression of IL-17A in the Wistar-RA rat model is higher, while the Lewis-RA model has a highly expressed VEGF,which may be related to its pathological characteristics.

Observation on the sensitivity of Wuzhishan, Tibetan and Bama minipigs to exogenous fats / 中国比较医学杂志

Objective To observe the sensitivity of Wuzhishan, Tibetan and Bama minipigs to exogenous fats.Methods A total of 15 male minipigs including 5 WZS minipigs, 5 Tibetan minipigs and 5 Bama minipigs, were used in this study.The minipigs were intravenously injected with fat emulsion and fed with high-fat diet, and the changes of serum total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and triglyceride (TG) levels were detected at 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h and 3 h after intravenous injection of fat emulsion and at 3 h and 12 h, 24 h, 36 h, 48 h, 60 h, 72 h and 84 h after fed with high-fat diet, respectively, and calculated the changes of area under the curve (ΔAUC) values.Results The triglyceride (TG) in the three kinds minipigs were significantly increased (P Wuzhishan minipig > Bama minipig, while TC, LDL-C and HDL-C showed no significant changes (P>0.05).Moreover, TC, LDL-C, HDL-C and TG were significantly increased in the three stocks of minipigs induced by feeding with high-fat diet (P Bama minipigs > Tibetan minipigs.Conclusions The three stocks of minipigs are sensitive to TG after intravenous injection of fat emulsion, and the lipid tolerance values are in an order of Tibetan minipig > Wuzhishan minipigs > Bama minipigs.Meanwhile, the three stocks of minipigs are also sensitive to TC, LDL-C and HDL-C after feeding with high-fat diet, and the lipid tolerance values are in an increasing order of Wuzhishan minipig > Bama minipigs > Tibetan minipigs.

Baicalein induces autophagy in breast cancer cells / 中国病理生理杂志

AIM: To investigate the autophagy of breast cancer cells induced by baicalein and to explore its mechanism.METHODS: The effects of baicalein on the viability of MCF-7 cells and 4T1 cells were investigated by MTT assay, and the dosage of the drug was determined.The expression levels of microtubule-associated protein 1 light chain 3-II (LC3-II) and LC3-I in the MCF-7 cells and 4T1 cells treated with baicalein at doses of 25, 50 and 100 μmol/L, or combined with autophagy inhibitor 3-methyladenine (3-MA) were determined by Western blot.In order to confirm the role of baicalein in autophagy, the effect of 3-MA on the apoptosis of both MCF-7 cells and 4T1 cells induced by baicalein was analyzed by flow cytometry.The protein levels of p-mTOR, mTOR, p-AKT and AKT were examined by Western blot and the role of AKT-mTOR pathway in the induction of autophagy in breast cancer induced by baicalein was determined by the combination of activators.RESULTS: Baicalein at 50 μmol/L and above doses significantly inhibited the viability of breast cancer cells in a dose-and time-dependent manner.The expression of LC3-II/LC3-I in both MCF-7 cells and 4T1 cells was significantly enhanced after the action of baicalein, and the ratio of LC3-II/LC3-I was significantly decreased after 3-MA addition.The results of flow cytometry showed that, compared with baicalein group, the combination of baicalein and 3-MA promoted the levels of necrosis and apoptosis.Moreover, the protein levels of p-mTOR and p-AKT were significantly decreased and were rescued by EGF, while their total protein levels were not changed.CONCLUSION: Baicalein induces autophagy through AKT-mTOR pathway both in MCF-7 cells and 4T1 cells.

Establishment of a Wuzhishan minipig model of atherosclerosis induced by high fat/cholesterol diet and regulation of Lp-PLA2 expression / 中国实验动物学报

Objective To establish a Wuzhishan minipig model of atherosclerosis(AS) induced by high fat/cholesterol diet,and observe the changes of expression of lipoprotein associated phospholipase A2(Lp-PLA2) in plasma and plaques.Methods 10 Wuzhishan minipigs were randomly divided into 2 groups:The normal control(Ctr,n=4) group was fed with normal diet,and AS model(n=6) group fed with high fat/cholesterol diet for 24 weeks.After the modeling for 24 weeks,the changes of total cholesterol(TC),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C),triglyceride(TG),C-reactive protein(CRP),Lp-PLA2 activity and composition were detected.The changes of vascular lipid deposition and plaques were assessed by pathology using oil red O staining and HE staining,respectively,and immunohistochemical staining for IL-6 protein expression.Moreover,the expression of Lp-PLA2 mRNA determined by RT-PCR and protein by Western blot were observed in the abdominal aortic tissues.Results Compared with the control group,the body weight,body mass index(BMI),TC,LDL-C,HDL-C,CRP,Lp-PLA2 activity and composition and aortic lipid deposition were significantly increased,and AS plaque formation was observed in the AS model group(P<0.05,P<0.01).The expression of Lp-PLA2mRNA and protein and IL-6 protein in abdominal aortic tissues were also significantly increased(P<0.05).Conclusions Long-term high fat/cholesterol diet feeding for 24 weeks can induce atherosclerosis in Wuzhishan minipigs,and Lp-PLA2 plays a key role in the vascular inflammation and plaque formation.

Study on the protective effect of Guanxinning Tablet on myocardial ischemia reperfusion injury in rats / 中国比较医学杂志

Objective To observe the effect of Guanxinning Tablet (GXNT) on myocardial infarction and cardiac autonomic nervous function in rats with myocardial ischemia reperfusion injury (MI/RI).Methods Seventy SD rats were divided into 7 groups randomly (n=10);the sham group, the MI/RI group, 75 mg/kg, 150 mg/kg, 300 mg/kg and 600 mg/kg GXNT groups and 300 mg/kg Compound Danshen Tablets (DST) group.All rats were administered orally for 7 days, and then the MI/RI model was made by ligating the left anterior descending branch of coronary artery in rats.The changes of electrocardiogram were recorded and the electrocardiogram of J points and heart rate variability (HRV) parameters were analyzed.At the end of reperfusion, the myocardial infarct size was measured by using Evans blue and tetrazolium chloride (TTC) double staining, and pathological changes of myocardium were observed by HE staining.The changes of serum lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA) and nitric oxide (NO) levels were also detected.Results Compared with MI/RI group, GXNT and DST groups were significantly reduced myocardial infarct size and inhibited the rising of serum LDH and CK activities (P < 0.05, P < 0.01), and also reduced the total or average value of J point during reperfusion (P < 0.05, P < 0.01).Meanwhile, GXNT and DST groups were markedly increased HRV and serum NO level as well as decreased serum MDA content (P < 0.05, P < 0.01), and improved myocardial tissue pathology.Conclusions GXNT can reduce the myocardial infarction in rats with MI/RI, and also improve the cardiac autonomic nervous function.

Preliminary observation of the anatomical structures of the brain in WHBE rabbits by 3.0 T magnetic resonance imaging system / 中国实验动物学报

Objective To observe the morphological structures of WHBE rabbit brain in vivo based on 3.0 T magnetic resonance imaging system (MRI), accumulate the basic biological data of WHBE rabbit brain imaging, and provide a background information to further expand the WHBE rabbit application.Methods Nine healthy adult male WHBE rabbits were intravenously anesthetized with 3% pentobarbital sodium.3.0 T MRI plus rabbit brain dedicated coil was used to perform routine transverse and sagittal scans, and the size of brain structures were measured.Results MRI scanning can be successfully performed to obtain sagittal and transverse T2WI or T1WI images of WHBE rabbit brain in vivo, and can be clearly observed the basic structures of WHBE rabbit brains in vivo, such as olfactory bulb, cerebrum, cerebellum and pituitary gland.In addition, high signal was found in the hippocampus of the left and right temporal lobes in 4 rabbits with T2WI, but also low signal appeared in the corresponding regions in T1WI, and the others were not abnormal.Meanwhile, the reference data of frontal lobe, hippocampus, cerebrum, lateral ventricles, pituitary gland and other related anatomical structures were also obtained.Conclusions Using the 3.0 T magnetic resonance imaging system and rabbit brain coil,the morphological and anatomical structures of rabbit brain can be clearly observed, and the basic imaging data of WHBE rabbits brain have been established preliminarily.

Establishment of chronic myocardial ischemia model in minipigs and application of noninvasive telemetry technique / 中国比较医学杂志

In order to establish the minipig model of chronic myocardial ischemia and apply non-invasive telemetry technique, the minipig model of chronic myocardial ischemia was made induced by Vitamin D3, isoproterenol and combined with high fat diet, and the non-invasive telemetry technique was used to detect and evaluate the symptoms of minipig model of chronic myocardial ischemia.Moreover, the effects of transport stress and the risk factors of atherosclerosis (AS) induced by high fat diet among Wuzhishan minipigs, Bama minipigs and Tibetan minipigs were also evaluated.Our study has successful established the Bama minipig model of chronic myocardial ischemia and the technical specification for evaluation,.The non-invasive telemetry technique can be used to detect and evaluate the symptoms of chronic myocardial ischemia model, and defines minipigs at least need to keep for more than 4 weeks after transport stress to adaptive recovery period.In addition, the different characteristics of AS risk factors such as hyperlipidemia, hypertension and hyperinsulinemia were observed in Wuzhishan minipigs, Bama minipigs and Tibetan minipigs in high fat environment, and this provides a reference for the selection and application of minipigs in the research of cardiovascular diseases.

Establishment of a rat model of chronic heart failure by transverse aortic constriction and observation of its pathological process / 中国比较医学杂志

Objective To observe the pathological changes of heart failure caused by transverse aortic constriction in rats.Methods Partial thoracotomy was performed to the second rib and the transverse aortic constriction was performed between the innominate and left carotid arteries to establish a model of heart failure in 24 rats.The same operation was performed on another 8 rats, except for the ligation of the transverse aorta.Echocardiographic assessment, hemodynamic measurement, myocardial histopathological examination and NT-proBNP measurement were performed to the sham group at 12 weeks and model group at 4 weeks, 8 weeks, 12 weeks after the operation.Result At 4 weeks after the operation, NT-proBNP, EF, FS and -dp/dtmax of the model group was significantly increased and LVESV, +dp/dtmax of the model group were significantly decreased (P<0.05).At 8 weeks after the operation, EF and-dp/dtmax of the model group were increased and +dp/dtmax of the model group was significantly decreased (P<0.05).At 12 weeks after the operation, NT-proBNP, EF and +dp/dtmax of the model group were decreased, and LVESV, LVEDV and -dp/dtmax of the model group were increased (P<0.05).The cardiomyocytes became hypertrophic and lined up in disorder at 4 weeks after the operation.Pathologic examination of the myocardial tissue showed connective tissue proliferation and inflammatory cell infiltration at 8 weeks after the operation, and cardiomyocyte apoptosis and collagen fiber deposition at 12 weeks after the operation.Conclusions Transverse aortic constriction induces heart failure in rats.The pathological processes are compensatory hypertrophy at 4 weeks after the operation, initial reaction of decompensation at 8 weeks after the operation, and heart failure at 12 weeks after the operation.

"Changes of the mRNA expression of ""kidney yang deficiency""-related genes and ultrastructural observation of the hypothalamus in Lewis rats" / 中国实验动物学报

Objective To observe the changes of mRNA expression related to kidney yang deficiency and the ul-trastructure of hypothalamus in Lewis rats, and further study the constitution of kidney yang deficiency in Lewis rats.Meth-ods Ten 7-8-week old SPF male Lewis rats and twenty 7-8-week old SPF male Wistar rats were used in this study.The rats received subcutaneous injection of hydrocortisone to establish kidney yang deficiency model.The expressions of TNF-α, IFN-γ, IL-10, CRH, MR and GR mRNA in the hypothalamus of the two groups were detected and the ultrastructural changes of hypothalamus and adrenal gland were observed to compare the differences between the two groups, and to ex-plore the mechanism of kidney yang deficiency constitution in the Lewis rats.Results Compared with the normal Wistar rats, the expressions of GR and IL-2 mRNA in the hypothalamus were significantly increased ( P<0.01 ) , while the ex-pressions of CRH, TNF-α, IFN-γand IL-10 mRNA were significantly decreased in the Lewis rats (P<0.01).The zona fasciculata of the adrenal cortex was slightly thinner, the mitochondria were slightly swollen and the amount of mitochondria was decreased.The nuclei of hypothalamic neurons were larger, and the mitochondria, neuron synapses and secretory vesi-cles in the presynaptic neurons were decreased.Conclusions There are abnormal expression of immune-related cytokines and CRH mRNA, and ultrastructural changes in the hypothalamus and adrenal gland of Lewis rats with kidney yang defi-ciency.Such changes may be related to the functional imbalance of the hypothalamus-pituitury-adrenal axis.

Establishment of a zebrafish model of thrombosis and the intervention effect of Guanxinning tablet / 中国实验动物学报

Objective To establish a zebrafish model of thrombosis induced by three kinds of inducers and observe the anti?thrombotic effect of a Chinese traditional medicine, Guanxinning tablet ( GXN) . Methods The zebrafish models of thrombosis was induced by using 1?5μmol/L phenyl hydrazine, 80μmol/L arachidonic acid and 5 mg/L ponatinib, re?spectively, and were treated with various concentration of GXN, clopidogrel or asprin. The thrombus in the tail vein was observed under microscope, Erythrocytes in the zebrafish heart were stained with o?dianisidine and the erythrocyte staining intensity was assessed with a NIS?Elements DTM image analyzer, and the anti?thrombolic effect of GXN was calculated. Results Venous thrombus was significantly increased and the staining intensities of erythrocytes in the heart were signifi?cantly decreased after induction by phenyl hydrazine, arachidonic acid or Ponatinib ( P <0?001 ) , respectively. At the same time, GXN showed an incresing anti?thrombolic effect in the zebrafish models (P<0?001) in a dose?effect manner, with a IC50 of GXN of 44?32 mg/L,138?5 mg/L and 459?5 mg/L, respectively. Conclusions The zebrafish models of thrombosis are successfully established by phenyl hydrazine, arachidonic acid or Ponatinib, respectively, by different for?mation mechanisms. GXN has been shown to have an anti?thrombosis effect, probably, by multiple target effects.

Establishment of a minipig model of chronic myocardial ischemia of phlegm-blood stasis syndrome type / 中国比较医学杂志

ObjectiveToestablishadiseasesyndromecombinedanimalmodel,theminiaturepigmodelof chronic myocardial ischemia of phlegm-blood stasis syndrome type , by high fat/cholesterol diet feeding and intravenous injection with VD3 and isoproterenol.Methods Miniature pigs were randomly divided into the control (Ctr) group, high fat/cholesterol diet ( HFC) group and chronic myocardial ischemia model of phlegm-blood stasis syndrome ( CMI) group, 5 pigs in each group .The Ctr group was fed with normal regular chow diet , HFC group was fed with high fat/cholesterol diet , while the CMI group was fed with high fat/cholesterol diet and intravenous injection with VD 3 and isoproterenol .The experiment lasted for 24 weeks.The model establishment and its pathological process of phlegm-blood stasis syndrome were evaluated by examinations of body weight , electrocardiogram, activity, blood lipid, myocardial enzymes, hemorheology, inflammation, cardiac index(CI) and myocardial ischemia size (MIS).Results Compared with the Ctr group, the body weight, heart rate(HR), Total cholesterol(TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol ( HDL-C ) , atherosclerosis index ( AI ) , low/middle/high shear rate of whole blood viscosity and reduced viscosity, erythrocyte electrophoresis time(EPT), high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels in the HFC group were significantly increased (P <0.05, P <0.01), while the body weight, heart rate, total ST, ST_average, activity, TC, TG, LDL-C, HDL-C, AI, CK, LDH, cTn-1, low/middle/high shear rate of whole blood viscosity and reduced viscosity, EPT, Casson viscosity(CV), hs-CRP, IL-6, CI and MIS in the CMI group were significantly increased (P<0.05, P<0.01), and APN level in the CMI group was significantly decreased (P<0.05).Moreover, AI, CK, LDH, cTn-1, low/middle/high shear rate of whole blood viscosity , EPT, CI and MIS in the CMI group were significantly higher than those of HFC group (P<0.05, P<0.01), while APN in the CMI group was significantly lower than that of HFC group (P<0.05).Correlation analysis showed that MIS was closely correlated to TC , LDL-C, AI, CK, LDH, cTn-1, APN, high/middle/low shear rate of whole blood viscosity , EPT, CV, hs-CRP and IL-6 (P<0.05, P<0.01).The linear regression analysis also showed that phlegm-blood stasis was closely correlated to TC , LDL-C, AI, CK, LDH, cTn-1, APN, CV, EPT, hs-CRP, and IL-6 ( P <0.01), and further linear stepwise regression analysis showed that the evolution of phlegm-blood stasis was closely related to TC , CK and IL-6.Conclusions Minipig model of chronic myocardial ischemia of phlegm-blood stasis syndrome type can be established by high fat /cholesterol diet feeding and intravenous injection with VD 3 and isoproterenol .Their blood lipid metabolism , hemorheology , myocardial enzymes and inflammatory indexes can be used as external biochemical basis of phlegm-blood stasis syndrome type , which may reflect related biological basis of the traditional Chinese medicine theory of “phlegm and stasis cementation , blood-stasis & toxin causing catastrophe”.

Experimental research on the prevention of rabbit postoperative abdominal cavity adhesion with PLGA membrane / 生物医学工程学杂志

The aim of this paper is to explore the prevention of rabbit postoperative abdominal cavity adhesion with poly (lactic-co-glycotic acid) (PLGA) membrane and the mechanism of this prevention function. Sixty-six Japanese white rabbits were randomly divided into normal control group, model control group and PLGA membrane group. The rabbits were treated with multifactor methods to establish the postoperative abdominal cavity adhesion models except for those in the normal control group. PLGA membrane was used to cover the wounds of rabbits in the PLGA membrane group and nothing covered the wounds of rabbits in the model control group. The hematologic parameters, liver and kidney functions and fibrinogen contents were detected at different time. The rabbit were sacrificed 1, 2, 4, 6, 12 weeks after the operations, respectively. The adhesions were graded blindly, and Masson staining and immunohistochemistry methods were used to observe the proliferation of collagen fiber and the expression of transforming growth factor β1 (TGF-β1) on the cecal tissues, respectively. The grade of abdominal cavity adhesion showed that the PLGA membrane-treated group was significant lower than that in the model control group, and it has no influence on liver and kidney function and hematologic parameters. But the fibrinogen content and the number of white blood cell in the PLGA membrane group were significant lower than those of model control group 1 week and 2 weeks after operation, respectively. The density of collagen fiber and optical density of TGF-β1 in the PLGA membrane group were significant lower than those of model control group. The results demonstrated that PLGA membrane could be effective in preventing the abdominal adhesions in rabbits, and it was mostly involved in the reducing of fibrinogen exudation, and inhibited the proliferation of collagen fiber and over-expression of TGF-β1.

Hematologic toxicity of Gynura segetum and effects on vascular endothelium in a rat model of hepatic veno-occlusive disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the effects ofGynura segetum in rats with hepatic veno-occlusive disease (HVOD).</p><p><b>METHODS</b>Sixty Sprague-Dawley rats were assigned to a blank control group, one of three Gynura segetum treatment groups (low-dose group, 5.0 g/kg; mid-dose group, 10 g/kg; high-dose group, 20 g/kg), or a pseudo-drug group (10 g/kg of pseudo-ginseng). After 28 days of treatment, effects on white blood cell count, coagulation, secreted factors from vascular endothelium, and histopathology of the spleen were observed and inter-group differences were statistically assessed.</p><p><b>RESULTS</b>After the 4-week administration, all rats in the Gynura segetum treatment groups showed decrease in body weight, increases in numbers of leukocytes, neutrophils, lymphocytes, monocytes and eosinophils.decreases in platelets and platelet hematocrit, and increases in mean platelet volume and platelet distribution.In addition, the Gynura segetum treatments increased the prothrombin time, activated partial thromboplastin time, thrombin time, prothrombin ratio and international normalized ratio, but decreased the PT%, fibrinogen level and platelet aggregation.Serum levels of endothelin and nitric oxide were also elevated by the Gynura segetum treatments.All measured parameters showed significant differences from the control group (P less than 0.01 or less than 0.05).Finally, the splenic follicles were significantly reduced and the spleens showed an absence of germinal centers along with a large number of diffuse lymphocytes and reduced red pulp sinusoids.</p><p><b>CONCLUSION</b>The Gynura segetum treatment has some toxic effects; it can reduce platelet count and platelet hematocrit, inhibit blood clotting time and platelet aggregation, increase the secretion of factors from the vascular endothelium and disrupt spleen histology.</p>

Methodological research of establishing atherosclerosis model with ballon injury plus high-fat diet and vitamin D3 in rats / 中国比较医学杂志

Objective To compare the effects of forming atherosclerosis by conducting ballon injury operation after 1th, 2th and 3th week of Vitamin D3(VD3) i.p., exploring the best method for atherosclerosis modeling .Methods 36 male rats were selected for balloon-injured carotid artery .SD rats were divided into 4 groups randomly:control group ( n=6), Model group1 (n=10), Model group2(n=10), Model group3 (n=10).Control group were fed up with common diet.Model groups were fed up with high-fat diet and injected 4.0 ×105 IU/kg VD3 through enterocoelia in the beginning , followed by the balloon-injured left carotid artery operation after 1th, 2th and 3th week respectively and 1.0 ×105 IU/kg VD3injection at 0th, 2th week after operation.The rats were killed at 4th week after operation.The serum levels of TG, TC, HDL-C and LDL-C were checked .ELISA was used to detect the content of hsCRP , IL-6 and TNFα.HE staining was used to observe the pathological changes in the thoracic aorta , and the thoracic aorta thickness , plaque area ( PA) , cross-sectional area of vessel ( CVA) and the ratio of PA to CVA ( PA/CVA) were analyzed .Results After 4 weeks of operation , levels of TC and LDL-C were significantly increased in Model group 2 and 3 compared with that of the control group ( P<0.05).Furthermore, contents of hsCRP, IL-6 and TNFαof model groups were also seriously higher than that of the control group (P<0.05), and that of Model group 3 were the highest.Typical AS plagues were observed in different degrees in model groups, and thoracic aorta thickness and PA/CVA were obviously increased than that of control group (P<0.05). Model group 3 turned out masses of lipid foam cells accumulated , and PA, CVA and PA/CVA were significantly increased than that of Model group2 or 3.Conclusion The AS model can be established successfully in rats with ballon injury after 3 weeks of high-fat diet plus VD3 i.p., which is the ideal method to induced atherosclerosis model .