1.Establishment of a Wuzhishan minipig model of atherosclerosis induced by high fat/cholesterol diet and regulation of Lp-PLA2 expression
Jing WANG ; Yongming PAN ; Xiaoping XU ; Yueqin CAI ; Fangming CHEN ; Zhaowei CAI ; Minli CHEN
Acta Laboratorium Animalis Scientia Sinica 2017;25(2):194-200
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.
2.Effects of salvianolic acid A injection on CCl4 induced hepatocyte injury and hepatic fibrosis in rats
Ting LU ; Fangming CHEN ; Keyan ZHU ; Yueqin CAI ; Qiyang SHOU ; Yongming PAN ; Minli CHEN
Chinese Journal of Comparative Medicine 2014;(7):57-62
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 .
3.Measurement of physiological parameters in Bama minipigs by telemetry technology
Liang CHEN ; Yongming PAN ; Keyan ZHU ; Fangming CHEN ; Xiaoping XU ; Minli CHEN
Chinese Journal of Comparative Medicine 2014;(7):30-36
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 .
4.Effects of testosterone deficiency on serum lipid levels and hepatic lipid accumulation in miniature pigs fed a high-fat diet
Zhaowei CAI ; Yongming PAN ; Liang CHEN ; Keyan ZHU ; Fangming CHEN ; Yueqin CAI ; Xiaoping XU ; Minli CHEN
Chinese Journal of Comparative Medicine 2015;(1):40-44
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.
5.Experimental research on the prevention of rabbit postoperative abdominal cavity adhesion with PLGA membrane.
Xiubing PANG ; Yongming PAN ; Fei HUA ; Chaoying SUN ; Liang CHEN ; Fangming CHEN ; Keyan ZHU ; Jianqin XU ; Minli CHEN
Journal of Biomedical Engineering 2015;32(1):146-162
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
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surgery
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Animals
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Collagen
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metabolism
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Lactic Acid
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Polyglycolic Acid
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Rabbits
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Tissue Adhesions
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prevention & control
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Transforming Growth Factor beta1
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metabolism
6.Establishment of chronic myocardial ischemia model in minipigs and application of noninvasive telemetry technique
Minli CHEN ; Yongming PAN ; Liang CHEN ; Xiaoping XU ; Dejun WANG ; Yuwei YANG ; Fangming CHEN ; Yueqin CAI ; Jianqin XU ; Keyan ZHU
Chinese Journal of Comparative Medicine 2017;27(5):16-18
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.
7.Effects of PLGA absorbable membrane on preventing postoperative abdominal adhesion in rabbits.
Xiubing PANG ; Yongming PAN ; Fei HUA ; Chaoying SUN ; Liang CHEN ; Fangming CHEN ; Keyan ZHU ; Jianqin XU ; Minli CHEN
Chinese Journal of Medical Instrumentation 2014;38(5):389-392
OBJECTIVETo investigate the effects of PLGA absorbable membrane in prevention of postoperative abdominal adhesion in rabbits.
METHODS66 Japanese white rabbits were randomly divided into three groups: the normal control group n = 6, model control group n = 30 and PLGA group n = 30. Rabbits were received multifactor methods to establish postoperative abdominal adhesion models except for normal control group. The cecum wound was covered PLGA membrane in the PLGA group. At postoperative 1, 2, 4, 6 and 12 weeks, the abdominal cavities were reopened and the adhesive severity was graded blindly, and the hydroxyproline level in cecum tissue was measured and the cecum histopathology was observed.
RESULTS(1) the degree of adhesion and hydroxyproline level in model control group were significantly higher than those of normal control group (P < 0.05, P < 0.01), while the degree of adhesion and hydroxyproline level in PLGA group were significantly lower than those of model control group (P < 0.05). (2) HE staining showed that cecum serosa had obviously inflammatory cell infiltration and fibroblast proliferation, while PLGA could inhibit fibroblast proliferation and reduce the inflammatory cell infiltration and collagen.
CONCLUSIONPLGA absorbable membrane can inhibit fibroblast proliferation and collagen to prevent the experimental postoperative peritoneal adhesions.
Abdominal Cavity ; pathology ; Animals ; Cell Proliferation ; Collagen ; analysis ; Fibroblasts ; cytology ; Lactic Acid ; chemistry ; Membranes, Artificial ; Polyglycolic Acid ; chemistry ; Postoperative Complications ; prevention & control ; Rabbits ; Tissue Adhesions ; prevention & control
8.Characterization of intestinal microflora in WHBE rabbit and Japanese white rabbit models of diarrhea-predominant irritable bowel syndrome
Xiaoping XU ; Jianqin XU ; Junjie HUANG ; Junping LIU ; Fangming CHEN ; Zhaowei CAI ; Yueqin CAI ; Yongming PAN
Acta Laboratorium Animalis Scientia Sinica 2018;26(2):165-173
Objective To compare the differences in the intestinal microflora of WHBE rabbit and JW rabbit models of diarrhea-predominant irritable bowel syndrome(IBS). Methods 16 WHBE rabbits and 16 JW rabbits were randomly divided into normal control(NC)group and IBS model group, respectively(n=8). The diarrhea-predominant IBS model was established by wet-heat stress combined with intragastric gavage of senna decoction. The abdominal circumference index,water content of feces and colonic transit function were observed. After sacrifice,colon tissue samples were taken for histopathological examination and colon contents for intestinal flora diversity analysis. Results Compared with the NC group,the IBS model rabbits showed an increased abdominal circumference index and fecal water content,and a shortened colon transit time, but no obvious pathological changes were observed in the colon tissues. Meanwhile, the Shannon index and Chao1 index of IBS model rabbits were significantly decreased(P<0.05). According to the result of OTU classification analysis,Firmicutes and Bacteroidetes are the dominant bacteria in the intestinal microflora of rabbits. Compared with the NC group, the Firmicutes, Verrucomicrobia, Chloroflexi, Akkermansia, and Streptococcus in the WHBE rabbit IBS model group were significantly reduced(P < 0.05, P < 0.01), while Bacteroidetes and rc4-4 significantly increased(P < 0.05, P < 0.01). However, in the JW rabbit IBS model group, Eubacterium and Subdoligranulum were significantly increased(P< 0.05),while Lactobacillus,Coprobacter,Veillonella and Streptococcus were markedly decreased(P<0.05). Compared with the JW rabbit NC group,the abundance of Firmicutes,Odoribacter, Veillonella,Streptococcus,Oscillospira and Pseudoflavonifractor were significantly decreased(P<0.05, P<0.01), but Bacteroidetes,Verrucomicrobia,Eubacterium,Akkermansia and Coprobacter were significantly increased(P<0.05,P<0.01)in the WHBE rabbit NC group. Compared with the JW rabbit IBS model group, the abundance of rc4-4, Bacteroidetes,Coprobacter and Clostridium were significantly higher(P < 0.05, P < 0.01), while the Firmicutes, Dorea, Coprococcus and Subdoligranulum were significantly lower(P <0.05)in the WHBE rabbit IBS model group. Conclusions There is an intestinal microflora imbalance in rabbits with IBS, resulting in a decrease of microflora diversity. The changes of intestinal microflora in the WHBE rabbits and JW rabbits with IBS have their own characteristics, and have apparent differences.
10.Efficacy evaluation of specific immunotherapy with standardized house dust mite allergen preparation for allergic rhinitis.
Jie ZHOU ; Yuanping HE ; Xudong ZENG ; Zewen LI ; Fangming PAN ; Yingchao CHEN ; Zhaolong LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(11):487-489
OBJECTIVE:
To evaluate the efficacy of specific immunotherapy (SIT) with standardized house dust mite allergen preparation for allergic rhinitis (AR).
METHOD:
Fifty-five patients with allergic rhinitis caused by house dust mites were selected in this self-control study. Clinical efficacy was evaluated by symptom and sign score after two years of specific immunotherapy and compared with pre-treatment scores.
RESULT:
After completing the study, a clinically significant reduction in symptom and sign score in these patients was noted, compared with that of pretreatment. And the difference was statistically significant (P < 0.01).
CONCLUSION
Standardized house dust mite allergen preparation is an effective treatment in patients suffering from allergic rhinitis due to house dust mites.
Allergens
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therapeutic use
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Animals
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Antigens, Dermatophagoides
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therapeutic use
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Female
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Humans
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Immunotherapy
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methods
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Male
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Pyroglyphidae
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immunology
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Rhinitis, Allergic
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therapy
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Treatment Outcome