1.Gene regulation of fatty acids oxidation enzymes in myocardium and the role of PPAR?
Chinese Journal of Pathophysiology 2000;0(12):-
The mammalian fetal heart relies primarily on glucose and pyruvate as substrates for ATP production, and it is rapidly transformed to fatty acid ?-oxidation (FAO) postnatally. However, energy metabolic pathways revert to a fetal pattern, when cardiac hypertrophy and heart failure developed. This return was called recapitulation, ultimately it is maladaptive for the body. The process of FAO was performed under a precise regulating system, nuclear transcription factors such as PPAR?, Sp1/3, Coup-TF(chicken ovalbumin upstream promoter transcription factor) all take part in the regulation of genes transcription of FAO enzymes. It was identified that the reguction of PPAR? activity in hypertrophic myocardium due to pressure overload might result in down-regulation of gene expression of FAO enzyme. The mechanism involved in reinduction of a fetal gene transcription participated in the regulation of myocardial energy metabolism in the development of cardiac hypertrophy resulting from pressure overload.
2.Role of carvedilol on energy metabolic reversion and rem odeling of pressure overload-induced left ventricular hypertrophy in rats
Chinese Journal of Pathophysiology 1986;0(02):-
AIM: To study changes of medium chain acyl- Co A dehydrogenase (MCAD), muscle carnitine palmitoyltransferase I (M-CPT-I) and co lligin mRNA/protein expression, to elucidate molecular mechanism of the recapit ulation of fetal energy metabolism and ventricular remodeling and the effects o f carvedilol during the development of pressure overload-induced left ventricula r hypertrophy in rats. METHODS: Male Wistar rats of hypertrophy induced by constrictio n of abdominal aorta (CAA) were randomized into 2 groups (n=12, each group): 4-week group (CAA 4 weeks group) and 12-week carvedilol intervention gro up (CAR group). Additi onal rats (n=12) underwent abdominal cavity incision without ligation to ser ve as age-matched sham operated controls (SH). Hemodynamics, ventricular remodel ing parameters and free fatty acid (FFA) both in blood serum and myocardium we re measured. RT-PCR analysis of the expression of mRNA of M-CPT-I, MCAD and col lagen binding protein (colligin) were investigated. The protein expression of co lligin was analyzed by Western blotting in the experimental animals and sham op eration.RESULTS: LVM/BW and MAP in CAA group were increased more signif icantly than in sham group. There were progressive increases in FAA both in bloo d serum and myocardium in CAA group than in sham group, accompanied with downreg ulation of gene expressions of M-CPT-I and MCAD and colligin mRNA/ protein upre gulation in LV in CAA group, while changes of all of these parameters in CAR gro up were attenuated. CONCLUSIONS: (1) The down-regulated expression of cardiac FAO en zyme genes (M-CPT-I and MCAD) in the hypertrophied heart may be responsible for "the recapitulation of fetal energy metabolism" during the development of pres sure overload-induced left ventricular hypertrophy in rats. (2) Carvedilol atten uates the reversion of the metabolic gene expression back towards fetal type. (3 ) Carvedilol is effective in regressing the left ventricular remodeling by inhi biting colligin protein expression. A molecular mechanism by which carvedilol ma y confer cardioprotective effects in heart failure may be, in part, via preservi ng o f the adult metabolic gene regulation and regressing left ventricular remodeling .
3.PPAR? expression and its effects on the differentiation of mesenchymal stem cells induced by 5-Azacytidine in vitro
Xianhe LIN ; Longgui LI ;
Journal of Third Military Medical University 1988;0(06):-
Objective To explore the expression of peroxisome proliferator activated receptor? (PPAR?) and its roles in the differentiation of mesenchymal stem cells (MSCs) induced by 5 Azacytidine. Methods 5 Azacytidine was used to induce the differentiation of primary cultured mesenchymal stem cells. The eukaryotic expression plasmid vector pEGFP N1 PPAR? was transfected into MSCs with lipotransfection method followed by G418 selection. The expression levels of PPAR? mRNA were detected by RT PCR. Immunohistochemistry and Western blot were employed to study the protein expression of PPAR?. Lipid droplets in the cells were stained with Oil Red O. Results No expression of PPAR? mRNA was found in undifferentiated MSCs. After induction by 5 Azacytidine, partial MSCs expressed PPAR? and differentiated into lipoblasts. MSCs, transfected with pEGFP N1 PPAR?2, differentiated into adipocytes. Conclusion 5 Azacytidine can induce the differentiation of MSCs into myoblasts and lipoblasts, which may be related to the expression of PPAR?.
4.Coronary stenting without predilatation in acute coronary syndromes
Lan HUANG ; Yaomin SONG ; Longgui LI
Chinese Journal of Interventional Cardiology 2001;0(S1):-
Objective The aim of this study was to asses the success rate, lesion characteristics and complication in acute coronary syndromes treated by direct coronary stenting Methods 92 patients with acute myocardial infarction and unstable angina were divided into the direct stenting ( n =32) and stent implantation with balloon predilatation (conventional stenting, n =60) groups The clinical data, characteristics of target vessels ,success rate and complications were compared between two groups Results The age in direct stenting groups was much younger than that in conventional stenting group (53 14?9 18 vs, 64 28?12 36, P
5.Effects of carvedilol on cardiomyocyte apoptosis and sarcoplasmic reticulum Ca~(2+) AT-Pase activity in rats with congestive heart failure
Zhaohua GENG ; Longgui LI ; Qiang WU ;
Journal of Third Military Medical University 2003;0(09):-
Objective To study the mechanism of carvedilol therapy of congestive heart failure. Methods After chronic heart failure model was established by ligation of the left coronary artery in rats, rats were treated with carvedilol and terazosin. Then hemodynamic parameters, activity of sarcoplasmic reticulum(SR) Ca 2+ pump(SERCA 2a ) and the rate of cardiomyocyte apoptosis were determined. Results Compared with those of the control group( group C), the activity of SR Ca 2+ pump in the heart failure group(group F) decreased( P 0.05). Carvedilol intervention reduced the rate of cardiomyocyte apoptosis, but enhanced the activity of SR Ca 2+ pump significantly in dose dependent manner. The activity of SR Ca 2+ pump was negatively correlated with the rate of cardiomyocyte apoptosis( r =-0.814, P
6.Effects of Perindopril on amount and mRNA expression of Ca2+ release channels of myocardial sarcoplasmic reticulum in rats with chronic heart failure
Zhaohua GENG ; Longgui LI ; Jian HUANG
Chongqing Medicine 2001;(1):13-14,17
Objective To study the effects of ACE1 on amount and mRNA expression of Ca2+ release channels(RyR2) of myocardial sarcoplasmic reticulum(SR) in prevention and treatment of chronic heart failure.Methods After the model of chronic heart failure was established with ligation of left corongary artery in rats,the animals were prevented and treated with Perindopril. Hemodynamic parameters, Bmax and Kd of [3H]-ryanodine binding to RyR2、RyR2 mRNA content were determined.Results Compared with the control group(group C),LVEDP in the heart faliure group (group F)increased(P<0.01),while+dp/dtmax and -dp/dtmaxdecreased significantly(P<0.01).LVEDP was lower but +dp/dtmax and -dp/dtmaxsignificantly higher in the Perindopril treated group(group P)than those in group F(P<0.01).Bmaxof [3H]-ryanodine binding to RyR2 and mRNA content of RyR2 in group F were lower than those in group C(P<0.01),and these in group P were higher than those in group F(P<0.01). There were no significant difference of Kd among the three groups(P>0.05).Conclusion The amount and mRNA expression of RyR2 of myocardial sarcoplasmic reticulum(SR) decreased in chronic heart failure.Perindopril can improve mRNA expression and amount of RyR2 of myocardial SR in prevention and treatment of chronic heart failure, thus contributing to the improvement of myocardial function.
7.Clinical observation of curing patients with congestive heart failure by metoprolol assistant with Shexiang Baoxing Pills
Guisheng ZHANG ; Xiangqing CHEN ; Longgui LI ; Tingting ZHANG
Chinese Traditional Patent Medicine 1992;0(12):-
AIM: To research clinical effect of curing patients with CHF(congestive heart failure) with Metoprolol and Shexiang Baoxing Pills(SBP). METHODS: 156 CHF patients were divided into three groups,including M(Metoprolol),SBP and M-SBP at random.The first dosage of Metoprolol was specified by the heart function,taking SBP 3 times per day and 2 pieces once,totally 8 weeks.Observeing Plasma Cyclic Nucleotide(Cyclic Adenosine monophosphate and Cyclic Guanosine Monophosphate),Norepinephrine(NE),Atrial Natriuretic Peptide(ANP) and Heart Ejection Fraction(EF),Cardiac Output(CO),heart and chest proportion,Before and after the curing. RESULTS: The curing effect of M-HMP group obviously surpasses simply M group and HMP group. CONCLUSION: Curing CFH patients by metoprolol assistant with SBP is better method.
8.Molecular mechanism of the reversion back towards fetal energy metabolism occurring with the development of cardiac hypertrophy and the role of Carvedilol
Qin HU ; Longgui LI ; Zhaohua GENG ; Feng JIN ;
Journal of Third Military Medical University 2003;0(16):-
Objective To study the reversion of the metabolic gene expression pattern of hypertrophic cardiac and role of Carvedilol and to explore the molecular regulatory mechanism of Carvedilol on attenuating the reversion back towards fetal energy metabolism occurring with the development of cardiac hypertrophy. Methods A model of hypertrophy induced by coarctation of abdominal aorta(CAA) in male Wistar rats was employed and changes of parameters such as hemodynamics, ventricular remodeling parameters, free fatty acid in blood serum and cardiac myocyte and expressions of muscle carnitine palmitoyltransferase Ⅰ (M CPT Ⅰ) and medium chain acyl CoA dehydrogenase (MCAD) mRNA were investigated in the experimental animals in operation group(CAA), sham operation group(SH) and Carvedilol intervention group(CAR) at 16 weeks after operation. Results Significant hypertrophy was found in the left ventricle in CAA group(3.41?1.30 vs 2.46?1.31, P
9.Effect of Shenxian Yiganling Tablets Combined with HBsAg Gene-modified Dendritic Cells on Immune Response and Hepatocyte Damage of Hepatitis B Virus Transgenic Mice
Shujie WANG ; Wei JIANG ; Longgui CHEN ; Chao LI ; Weijun GUO
Journal of Guangzhou University of Traditional Chinese Medicine 2015;(1):106-110
Objective To observe the effect of Shenxian Yiganling Tablets ( SYT) , a Chinese herbal recipe with the actions of tonifying kidney and removing toxicity, combined with HBsAg gene-modified dendritic cells (DC/HBsAg) on immune response and hepatocyte damage of hepatitis B virus (HBV) transgenic mice. Methods HBV transgenic mice ( Tg mice) were immunized with injection of DC/HBsAg ( 100 μg every three weeks) through caudal vein, and then were given intragastric administration of SYT in the dosage of 12.8, 23.5, and 47.0 mg/d for four weeks. HBV Tg mice splenic T cell cytokines of interleukin 2 ( IL-2) and interferon gamma ( IFN-γ) levels as well as serum alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) conents were detected by enzyme-linked immunosorbent assay ( ELISA) . Lactate dehydrogenase ( LDH) release assay was used to detect the in-vitro cytotoxic activity of splenic HBsAg specific T lymphocytes. Serum HBsAg level of HBV Tg mice was detected by ELISA after immunization. Results Compared with DC/HBsAg administration alone, DC/HBsAg combined with SYT could significantly increase HBV Tg mice splenic T cells cytokines IL-2 and IFN-γ levels ( P<0.05 or P<0.01) , increase the cytotoxic activity of HBsAg-specific T lymphocytes ( P<0.05 or P<0.01), increase the inhibition rate of HBsAg expression (P<0.05 or P<0.01), and reduce hepatocyte damage. Conclusion SYT could enhance the immune response of Tg mice to DC/HBsAg immunization, and relieve the hepatic damage, which enable the HBV clearance process out of hepatic damage in the case of anti-HBV activity of IFN-γbeing unaffected.
10.Preoperative Evaluation of Mitral Vaive pathologywith Two-dimensional Echocardiography-An Analysis of 50 Cases
Rixing XU ; Longgui LI ; Shanjun ZHU ; Gongqing GAO ; Youxiang ZHANG
Journal of Third Military Medical University 1983;0(04):-
Fifty cases with chronic rheumatic valvular disease were examined with two dimensional echocardiography to evaluate the valvular pathology preoperatively. The echocardiographic findings were correlated and compared with the operative findings.It was found that 89% of the thickening pattern cases and 75% of the funnel-shaped cases showed thickening of the leaf-lets- All the 28 membranous cases showed diastolic doming and restricted tip motion of the anterior leaflet in different degrees. In the 4 funnel-shaped cases, 3 showed restricted tip and body motion of the leaflets and the 4th case showed stiffness of the leaflet base. 63% of the mitral regurgitation cases were confirmed at operation.It is concluded that preoperative evaluation of the valvular pathology with two dimensional echocardiography is helpful in selection of suitable operative candidates.