Objective The aim of this study was to explore the effect of androgen deficiency on serum hormone levels, visceral fat accumulation and inflammatory gene expression in miniature pigs fed a high-fat diet ( HFD) . Methods Sexually mature male Chinese Wuzhishan miniature pigs were divided into three groups ( animals/group) as follows:intact male pigs ( SHAM) , castrated male pigs ( CAS) and castrated male pigs plus testosterone treatment ( CAS+T) . The pigs were fed a HFD diet for 12 weeks. Serum levels of testosterone and leptin were measured and visceral fat were dissected and weighted. qRT?PCR was performed to determine the mRNA expression levels of lipogenic, lipolysis and inflammation relat?ed genes. Results (1) Serum testosterone levels were significantly decreased but serum leptin levels were significantly in?creased in the castrated pigs. These effects were recovered after testosterone treatment. ( 2 ) Visceral fat percentage was significantly increased in the castrated pigs, and testosterone treatment reduced the increased visceral fat in the castrated pigs. (3) Castration and testosterone treatment had no significant effects on the expression levels of lipogenic genes (FAS and ACC) and lipolysis genes (HSL and ATGL) in pigs fed a HFD. (5) Castration significantly induced the expressions of inflammatory genes including Leptin, CD68, CCL16, CCL23 and SAA, and testosterone treatment recovered the expres?sions of the above genes in the castrated pigs. Conclusions Castration?induced testosterone deficiency promotes visceral fat accumulation and upregulates the expression levels of inflammatory genes in miniature pigs fed a HFD. Moreover, tes?tosterone treatment ameliorates castration?induced visceral fat accumulation and inflammatory response in HFD?fed pigs.

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 .

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.

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<0.01), and reached a peak at 0.5 h after injection.The degree of elevation of ΔAUC values were different showing on increasing order: Tibetan minipig > 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<0.05, P<0.01).Among them, the TC and LDL-C of Wuzhishan minipigs peaked at 36 h, HDL-C peaked at 48 h and TG peaked at 24 h after feeding, respectively.TC, LDL-C and HDL-C in the Bama minipigs and Tibetan minipigs peaked at 48-60 h and TG peaked at 36 h after feeding, and the ΔAUC values of TC, LDL-C and HDL-C were in an increasing order of Wuzhishan minipigs > 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.

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”.

Objective The aim of this study was to explore the effect of testosterone deficiency on serum lipid levels and hepatic lipid accumulation in miniature pigs fed a high-fat diet (HFD).Methods Eighteen sexually mature male Chinese Wuzhishan miniature pigs (6~7 months old) were used in this study.The pigs were divided in three groups ( n =6 animals/group ) as follows: intact male pigs , castrated male pigs and castrated male pigs with testosterone replacement .They were fed a HFD diet for 12 weeks and body weights were recorded weekly .Serum levels of testosterone , total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were measured.Hepatic TG and TC levels were also determined , and liver tissues were embedded in paraffin and stained with hematoxylin and eosin (H&E).Results (1) The body weights of pigs in each group were found to be linearly elevated over time .Though castrated pigs gained less weight than did pigs in the other groups , no significant differences were found between them .( 2 ) Castration caused a significant decrease in serum testosterone levels in pigs . This effect was recovered by testosterone treatment .(3) Serum levels of TC, LDL-C and TG were significantly increased in castrated pigs.However, castration had no significant effect on serum HDL-C levels.Testosterone treatment reduced the increased serum lipids in castrated pigs .(4) Hepatic TG and TC contents in castrated pigs were also significantly higher than those in other groups of pigs .Testosterone treatment reduced the increased hepatic lipids in castrated pigs .( 5 ) Compared with other groups of pigs , castrated pigs showed increased steatosis .However , testosterone treatment attenuated hepatic steatosis in castrated pigs .Conclusion Testosterone deficiency caused severe dyslipidemia , and increased hepatic lipid accumulation in miniature pigs fed a high-fat diet.

Objective To study on the anti-hepatic fibrosis effects of salvianolic acid A injection (SAA), and further to provide the theoretical basis for the clinical application .Methods Using CCl4 induced hepatocyte injury in vitro, the hepatocyte viability , the levels of ALT , AST and LDH in cell culture supernatants and the levels of SOD and MDA in cell lysates were detected .In addition , the hepatic fibrosis rat model was made by subcutaneous injection of CCl 4 , the serum LN, HA, SOD and MDA levels were detected and the pathological changes in liver tissue were also observed . Results Compared with model group , the hepatocyte viability in SAA high or low dose group and Vit E group were significantly increased (P <0.01), and the activities of ALT, AST and LDH in SAA high dose group were significantly lowed ( P <0.01 ) .The activity of SOD in SAA high dose group and Vit E group was significantly increased ( P <0.05), while MDA content was decreased (P <0.05).Vivo test showed that the levels of serum LN and HA in SAAhigh dose group were significant lower than those of hepatic fibrosis rat model group (P <0.05).Moreover, the activity of SOD in SAA high or low dose group was significantly increased (P <0.05, P <0.01), while MDA content was lowed (P <0.05, P <0.01), and can improve the pathological of liver tissues .Conclusions SAA injection can anti-lipid peroxidation and thereby protect hepatocyte and reduce hepatic fibrosis .

Objective To measure the circadian rhythm of consecutive monitoring electrocardiogram ( ECG ) , blood pressure, respiration, activities in Bama minipigs by telemetry technology .Methods Six 6-month-old Bama minipigs were implanted with VAP port in Superficial femoral artery , after recovery 7 days , 24 hours ECG , blood pressure, activity and respiratory parameters were recorded and analyzed in the EMAK noninvasive telemetry system . Results The ECG, blood pressure, respiration and activities in Bama minipigs showed circadian rhythm changes , Bama minipigs daytime heart rate was significantly higher than the nighttime heart rate (P <0.01), and daytime PR interval , QRS interval and QT interval was significantly lower than the nighttime (P <0.05, P <0.01), daytime mean heart rate was 76.22 beats/min, nighttime mean heart rate was 67.03 night beats/min;daytime mean PR interval , QRS interval andQT interval were 109.97 ms, 42.72 ms and 380.37 ms, nighttime mean PR interval , QRS interval and QT interval were 112.32ms, 44.01ms and 389.24ms.Bama minipigs daytime systolic blood pressure , diastolic blood pressure and mean blood pressure were significantly higher than the nighttime ( P <0.01 ) , daytime mean systolic blood pressure , diastolic blood pressure and mean blood pressure were 129.57 mmHg, 96.75 mmHg and 111.73 mmHg, nighttime mean systolic blood pressure , diastolic blood pressure , mean blood pressure were 122.81 mmHg, 92.65 mmHg and 106.19 mmHg, and the nighttime reduction rate of systolic blood pressure , diastolic blood pressure and mean blood pressure were 19.89%, 19.05%and 19.35%.In addition , Bama minipigs daytime activity and respiratory rate were significantly higher than the nighttime (P <0.01).Conclusion It’s Feasible to measure the circadian rhythm of electrocardiogram (ECG), blood pressure, activity and respiratory parameters in Bama minipigs by telemetry technology , and can truly shows those physiological parameters of the Bama minipigs within 24h, to provide a reference for pharmacology and toxicology research by using Bama minipigs .

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.

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.
Abdominal Cavity ; surgery ; Animals ; Collagen ; metabolism ; Lactic Acid ; Polyglycolic Acid ; Rabbits ; Tissue Adhesions ; prevention & control ; Transforming Growth Factor beta1 ; metabolism