1.Effects of pioglitazone on cardiac fibroblast proliferation induced with high glucose and high insulin
Keyan LIANG ; Hongxin WANG ; Pin BAO
Chinese Pharmacological Bulletin 2003;0(10):-
Aim To study effects of pioglitazone on cardiac fibroblast proliferation induced with high glucose and high insulin.Methods The neonatal rat cardiac fibroblasts were cultured and treated with different factors.The cellular number was determined by crystal violet uptake;the DNA synthesis was assayed with thymidine intake method;the percentage of S+G_2+M in the cell cycle was determined by flow cytometry.Results Pioglitazone inhibited the cell number、DNA synthesis and the percentage of S+G_2+M in the cell cycle of cultured cardiac fibroblasts induced with high glucose and high insulin.Conclusion Pioglitazone inhibits cardiac fibroblast proliferation induced with high glucose and high insulin and the effective mechanism of pioglitazone on cardiac fibroblast proliferation needs further study.
2.Establishment of a minipig model of chronic myocardial ischemia of phlegm-blood stasis syndrome type
Yongming PAN ; Liang CHEN ; Xiaoping XU ; Keyan ZHU ; Jianqin XU ; Minli CHEN
Chinese Journal of Comparative Medicine 2015;(9):1-7
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”.
3.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.
4.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 .
5.Observation on the sensitivity of Wuzhishan, Tibetan and Bama minipigs to exogenous fats
Liang CHEN ; Yongming PAN ; Keyan ZHU ; Xiaoping XU ; Jianqin XU ; Minli CHEN
Chinese Journal of Comparative Medicine 2017;27(6):12-16
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.
6.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
7.Safety study on jiazhu vascular ligating clips in rabbits after laparoscopic cholecystectomy
Xianhua CHEN ; Yongming PAN ; Yihong BAO ; Fei HU ; Xiubing PANG ; Liang CHEN ; Keyan ZHU ; Jianqin XU ; Minli CHEN
Chinese Journal of Comparative Medicine 2014;(9):32-39
Objective To provide an experimental reference for clinic application of Jiazhu vascular ligating clips on ligation effects and the impact on the body in rabbits after laparoscopoic cholecystectomy.Methods 36 rabbits were randomly divided into 3 groups, normal control group, Jiazhu group and similar product control ( Hem-o-lok) group, 12 rabbits in each group.Except for normal control group, the rabbits were used gallbladder duct and gallbladder artery closed by vascular ligating clips and Hem-o-lok clips in Jiazhu group and similar product control group, respectively.The changes of blood biochemical, electrolytes, hematological parameters, coagulation, ligation effects and organ coefficients were observed at post-operation during 12 months.Results Compared with normal control group, the rabbit weight was reduced in the Jiazhu group at 3 days postoperatively ( P <0.01 ) , ALT level was increased at 1week postoperatively ( P <0.05), CREA and ALB levels were all significant decreased at 1~2 weeks postoperatively (P <0.05, P <0.01), NEUT numbers and TG content were significant increased at 2 weeks postoperatively ( P <0.05 ) , GLU content was significant decreased at 2 weeks and 1 month postoperatively ( P <0.01 ); LYM and RBC numbers were significant decreased at 1 month and 1 week postoperatively (P <0.05), respectively.PLT numbers were significant increased at 1~2 weeks postoperatively ( P <0.01) .While the rabbit weight was reduced in the Hem-o-lok group between 3 days and 1month postoperatively (P <0.05, P <0.01), and ALT level, NEUT and PLT numbers were increased at 1 week postoperatively (P <0.05, P <0.01), ALB and GLU contents were all significant decreased at 2 weeks postoperatively (P <0.01), TC content was significant increased at 1~2 weeks postoperatively (P <0.05).The rabbit weight, blood biochemical and hematological parameters in the Jiazhu group and Hem-o-lok group were all no significant differences with normal control group in the remaining time ( P >0.05 ) , and there were all no significant differences with electrolyte, coagulation and organ coefficients between each group (P >0.05).Conclusion Jiazhu vascular ligating clips are safe and reliable to close gallbladder duct and blood vessels, It shows that there are no differences in the validity and security between Jiazhu vascular ligating clips and Hem-o-lok clips.
8.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.
9.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
10.Effect of lifestyle interventions on clinical outcomes of IVF/ICSI in overweight or obese patients with polycystic ovary syndrome
Xiaoli JIA ; Siying LIANG ; Keyan MIAO
Chinese Journal of Health Management 2023;17(12):916-920
Objective:To investigate the effect of lifestyle intervention on the clinical outcomes of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in overweight or obese patients with polycystic ovary syndrome (PCOS).Methods:This study was a non-randomized controlled trial. A total of 126 overweight or obese PCOS patients who received IVF/ICSI treatment for infertility in Shaoguan Maternal and Child Health Hospital from January 2021 to December 2022 were selected by semi-random sampling method. The patients were divided into the experimental group (39 cases) and the control group (87 cases) according to whether they received the comprehensive lifestyle intervention. The experimental group maintained a healthy lifestyle and emotional control, accepted balanced diet, performed aerobic exercise and resistance exercise regularly and quantitatively, the data changes related to body mass index were collected regularly. The control group implemented a weight loss regimen on their own, following a low-calorie diet and exercise interventions. After 2 to 3 months, both groups of patients entered the test tube cycle (the intervention duration for each patient was up to the effect and their willingness to weight loss). The baseline data, cycle characteristics and pregnancy outcomes were compared between the two groups with t test and Chi-square. And the effects of lifestyle interventions on the clinical outcomes of IVF/ICSI in overweight or obese PCOS patients were also analyzed. Results:Before the intervention, the serum level of anti-muller hormone (AMH) in the experimental group was significantly higher than that in the control group [(5.62±2.98) vs (4.47±2.64) μg/L]( P<0.05). But there were no significant differences in age, infertility years, basal follicle maturation hormone (FSH), antral follicle count (AFC), primary infertility ratio, ICSI ratio, body mass index, proportion of obese patients, abdominal circumference, waist-to-hip ratio, visceral fat area and body fat percentage between the two groups (all P>0.05). After intervention, the body mass index, proportion of obese patients, abdominal circumference, visceral fat area and body fat percentage in experimental group were all significantly lower than those before intervention [(26.56±2.92) vs (29.21±3.37) kg/m2, 25.64% vs 64.10%, (89.92±7.16) vs (95.27±7.38) cm, (78.46±15.92) vs (95.46±17.21) cm2, 33.71%±2.46% vs 36.27%±3.02%] (all P<0.05). After intervention, the visceral fat area in the control group was significantly lower than that before the intervention [(92.08±19.38) vs (98.84±19.65) cm2] ( P<0.05), and there was no significant differences in the other indexes (all P>0.05). After intervention, the total amount of gonadotropin (Gn) in experimental group was significantly lower than that in control group [(2 488.23±711.30) vs (2 935.67±854.78) U] ( t=2.301, P<0.05). Conclusion:A 2-3 month lifestyle intervention can significantly reduce the body mass index, waist circumference, visceral fat area, and body fat percentage of overweight or obese PCOS patients, as well as decrease the total amount of Gn used for ovulation induction. However, it does not show a significant improvement in clinical outcomes.