AIM: The impaired function of vascular endothelial cells occurs popularly in hypertensive patients. Hepatocyte growth factor (HGF) plays a crucial role on impaired function, and is related to prevalence, severity and target organ damages of hypertension. This study explored the relationship between HGF gene C57488A polymorphism and essential hypertension (EH). METHODS: ①Between June and December in 2006, totally 107 EH patients with an average age of (61?9) years, in them 47 cases with family history of hypertension, were recruited in this study. Informed consents were obtained from the patients who were all the Han residents of Hefei area, and the experiment was approved by the hospital ethical committee. The hypertension criteria formulated by Chinese Medical Association included the systolic pressure ≥140 mm Hg or diastolic pressure ≥ 90 mm Hg (1 mm Hg=0.133 kPa), or having received drug therapy for hypertension over one year. The patients were administrated with hypotensive drugs with one month. Meanwhile 110 normotensives without family history of hypertension and drug therapy were served as controls, with an average age of (60?8) years. Inclusion criteria: systolic pressure 0.05).②The distributions of HGF gene C57488A polymorphism were in agreement with Hardy-Weinberg equilibrium, indicating population representativeness. The frequencies of three genotypes CC, CA, AA were 0.809, 0.170, 0.021 and C, A alleles were 0.894, 0.106 in the EH group with family history respectively. Correspondingly, the frequencies were 0.733, 0.233, 0.033 and 0.850, 0.150 respectively in the EH patients without family history. Meanwhile, the frequencies were 0.527, 0.355, 0.060 and 0.705, 0.295 respectively in the controls.③The frequencies of genotype CC and allele C were both significant higher in EH with or without family history compared with the controls (P 0.05). CONCLUSION: HGF gene C57488A polymorphism is possibly associated with EH, and genotype CC and allele C may be the factors of genetic predisposition of EH in Han population of Hefei area.

Animals ; Calcium ; physiology ; Chloride Channels ; physiology ; Electrophysiological Phenomena ; Male ; Muscle, Smooth, Vascular ; cytology ; physiology ; Myocytes, Smooth Muscle ; physiology ; Pulmonary Artery ; cytology ; physiology ; Rats ; Rats, Wistar

Vascular endothelial growth factor (VEGF) plays an important role in tissues angiogenesis. The adaptation of animals to hypoxic environment is relative to the microvessel density (MVD) in tissues. To further explore the adaptation mechanisms of plateau zokor (Myospalax baileyi) to the hypoxic-hypercapnic burrows, the VEGF mRNA and the MVD in cerebral tissues of the plateau zokor were studied. Total RNA was isolated from liver, and VEGF cDNA was obtained by RT-PCR, then the VEGF cDNA was cloned and sequenced. The coding sequence of plateau pika (Ochotona curzniae), rat (Rattus norvegicus) and mouse (Mus musculus) VEGF cDNA are obtained from GenBank, and the nucleotide and amino acid sequence homology of plateau zokor VEGF cDNA coding sequence with that of plateau pika, rat and mouse were analyzed and compared by using of bioinformatics software. The VEGF mRNA was detected by real-time PCR, and the MVDs in cerebral tissues of the plateau zokor, plateau pika and Sprague-Dawley (SD) rat were measured by immunohistochemical staining. The results showed that the open reading frame of the plateau zokor VEGF was 645 bp, and the coding sequence of the plateau zokor VEGF cDNA shared 92.1%, 93.6% and 93.8% nucleotide sequence homology to that of the plateau pika, rat and mouse, respectively. The deduced amino acid sequence of the plateau zokor VEGF cDNA was composed of 188 amino acids and the amino acids from 1 to 26 were signal peptide sequence. The plateau zokor VEGF188 was 90.2%, 94.9% and 94.4% homologous to that of plateau pika, rat and mouse. The level of VEGF mRNA in brain of the plateau zokor was significantly lower than that of SD rat, but there was no obvious difference in VEGF mRNA level between plateau zokor and plateau pika. The MVD in brain of the plateau zokor was markedly higher than that of plateau pika and SD rat. In conclusion, plateau zokor enhances its adaptation to the hypoxic environment by increasing the MVD. The level of VEGF mRNA in the brain of plateau zokor is lower than that of SD rat, which may be as a result of inhibition by the higher concentration of carbon dioxide in the burrow.
Adaptation, Physiological ; physiology ; Amino Acid Sequence ; Animals ; Arvicolinae ; physiology ; Base Sequence ; Brain ; blood supply ; metabolism ; Hypoxia ; physiopathology ; Microvessels ; anatomy & histology ; Molecular Sequence Data ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Species Specificity ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in early atherosclerosis, vascular remodeling and development of atherosclerotic lesion. The potentially functional MMP-9 gene polymorphism may contribute to the susceptibility of acute coronary syndrome (ACS). This study aimed to investigate the association between two single nucleotide polymorphisms (-1562C>T, R279Q) of the MMP-9 gene in patients with ACS in the Uygur population of China. METHODS: This case-control study was composed of 361 ACS patients and 432 control subjects, who had undergone coronary angiography. Among the ACS patients, 162 (44.9％) had single-vessel disease, 145 (40.2％) had two-vessel disease, and 54 (14.9％) had three-vessel disease. The genotypes of the two selected SNPs were determined by the method of polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR). The relationship between the polymorphism of the MMP-9 gene and the severity of coronary arterial stenosis was analyzed. RESULTS: Analysis of the two SNPs showed that the frequency of CT and TT genotypes in patients with ACS was significantly higher than that in the control group (ACS vs. controls; CT+TT:25.5％ vs. 15.8％, P=0.001). And the -1562 gene allele (C/T) was significantly associated with acute coronary syndrome (ACS vs. controls; C allele: 85.7％ vs. 91.5％, T allele: 14.3％ vs. 8.5％, P<0.001). But the frequencies of CT+TT and CC genotypes were not statistically different among ACS patients with one, two and three or more significantly diseased vessels (P=0.55). The R279Q polymorphism site with regard to the association with ACS was not significant (P>0.05). The presence of CT or TT genotypes, assuming codominant effect of the T allele, was independently associated with increased risk of coronary artery disease when adjustment was made for age, body mass index, smoking, hypertension and diabetes mellitus [odds ratio=1.737 (95％ confidence interval, 1.337-2.257), P=0.018]. CONCLUSIONS: MMP-9-1562C>T polymorphism is associated with the susceptibility to ACS in the Uygur population of China. However, this mutation apparently is not related to the severity of coronary arterial stenosis. Another SNP (R279Q) polymorphism of MMP-9 is not significantly associated with the risk of ACS.

OBJECTIVETo investigate the association between the polymorphism of prostacyclin synthase gene (CYP8A1) and myocardial infarction (MI) in Uigur population.

METHODSTotally 210 patients with MI and 206 healthy control subjects were detected by polymerase chain reaction and restriction fragment length polymorphism. The serum 6-keto-PGF(1alpha) was detected with radioimmunoassay kit in all subjects.

RESULTSThe frequencies of CC, AC and AA were 0.024 (5/210), 0.124 (26/210) and 0.852 (179/210) in MI group while ones those 0.010 (2/206), 0.073 (15/206) and 0.917 (189/206) in the controls. There was no significant difference in frequencies of CC, AC and AA genotypes between controls and MI cases (chi(2) = 0.782, P > 0.05), but the frequency of CC + AC genotype in MI group [0.14 (31/210)] was higher than that in the controls [0.083 (17/206)] giving significant difference (chi(2) = 4.321, P = 0.031). The C allele frequency in the MI group [0.086 (36/420)] was higher than that in the controls [0.046 (19/412)] showing significant statistical difference (chi(2) = 5.284, P = 0.021). There was significant difference (t = 6.255, P < 0.01) in serum 6-keto-PGF(1alpha) level between MI group [(17.40 +/- 4.56) pg/ml] and control group [(20.34 +/- 5.02) pg/ml]. In the cases and control group, the serum 6-keto-PGF(1alpha) level of the persons with CC + AC genotype [(14.30 +/- 3.31) pg/ml, (18.31 +/- 4.62) pg/ml] was lower than those of AA genotypes [(19.34 +/- 5.51) pg/ml, (25.10 +/- 5.00) pg/ml], and the statistical significance was also observed (t' = 6.934, P < 0.05; t = 5.393, P < 0.01). Logistic regression analysis showed that the C allele of the CYP8A1 gene was an independent risk factor for MI (OR = 1.77; 95% CI: 1.06 - 2.05).

CONCLUSIONThe C allele of CYP8A1 might be a risk factor of MI in Uigur population, and be resulting from the decrease of serum 6-keto-PGF(1alpha) level for gene variation.

Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 Enzyme System ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Intramolecular Oxidoreductases ; genetics ; Male ; Middle Aged ; Myocardial Infarction ; ethnology ; genetics ; Polymorphism, Genetic ; Population Groups

OBJECTIVETo investigate the association between matrix metalloproteinase 9 gene (MMP9) -1562C/T polymorphism and myocardial infarction (MI) in Uighur population of Xinjiang.

METHODSA total of 347 patients with MI evidenced by coronary arteriography, and 403 controls free from coronary artery disease with normal angiograms were recruited for the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the -1562C/T functional promoter polymorphism of the MMP9 gene. The relationship between the polymorphism and the severity of coronary arterial stenosis was analyzed.

RESULTSThe results showed that the frequency of CT and TT genotypes in patients with MI (27.67%) was significantly higher than that in controls (14.14%). The frequencies of the -1562T allele were 15.71% and 7.56% in the MI group and the control group respectively (chi-square=24.57, P<0.01). Logistic regression analysis indicated that the T allele carriers (CT+TT) had significantly increased risk of MI compared with the CC carriers (OR=2.009, 95%CI: 1.250-3.230). Individuals carrying the -1562T allele with diabetes mellitus were at an increased risk of MI (OR=3.714, 95%CI: 1.299-10.773). The frequencies of CT and TT genotypes were not significantly different among MI patients with one, two and three or more significantly diseased vessels (chi-square=0.491, P=0.782).

CONCLUSIONThe -1562C/T polymorphism in the MMP9 gene promoter is associated with the susceptibility to MI in the Uighur population of Xinjiang. The T allele might be a risk factor of MI. And there was a coordinated effect between the -1562T allele and diabetes mellitus in the development of MI. The -1562C/T polymorphism may not be a predictor of the severity of coronary atherosclerosis.

China ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Matrix Metalloproteinase 9 ; genetics ; Middle Aged ; Myocardial Infarction ; enzymology ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the association between the polymorphisms and haplotypes of prostacyclin synthase gene with MI in Uigur patients in Xinjiang.

METHODS210 patients with MI and 206 healthy control subjects were genotyped for 3 SNPs of the human prostacyclin synthase gene by polymerase chain reaction and restriction fragment length polymorphism.

RESULTSThe genotype distributions of the control group and MI group were in the Hardy-Weinberg equilibrium (both P > 0.05). The frequency of CC of rs5629 in MI group was significantly higher than that in controls (71.42% vs. 61.65%, P = 0.035). The frequency of A-C-T haplotype was significantly higher in the control group than that in the MI patients (4.01% vs. 0.60%, P = 0.001). The frequency of C-T-T haplotype was significantly higher in the MI patients than that in the controls (7.40% vs. 3.31%, P = 0.011). Logistic regression analysis showed that, after adjusting hypertension, hyperlipemia and smoking, the CC genotype of rs5629 (P = 0.021, OR = 1.665, 95%CI: 1.024 - 2.156) and the C-T-T haplotype (P = 0.011, OR = 1.876, 95%CI: 1.410 - 3.171) was the independent risk factors for MI.

CONCLUSIONThe CC genotype of rs5629 and the C-T-T haplotype of prostacyclin synthase gene are associated with MI but the A-C-T haplotype of prostacyclin synthase gene might be a protective factor of MI in Uigur population of Xinjiang.

Aged ; Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 Enzyme System ; genetics ; Female ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Intramolecular Oxidoreductases ; genetics ; Male ; Middle Aged ; Myocardial Infarction ; ethnology ; genetics ; Polymorphism, Single Nucleotide

Objective The purpose of this study was to investigate the association of genetic polymorphism of cyclooxygenase-2 and prostacyclin synthase with myocardial infarction (MI)in Uigur population in Xinjiang. Methods 178 patients with MI and 175 healthy control subjects were detected on the genetic polymorphism of cyclooxygenase-2 and prostacyclin synthase by polymerase chain reaction-based restriction fragment length polymorphism. Other serum 6-keto-PGF1α concentration and biochemical indicators were detected in all the subjects. Results (1)The genotype distributions of the control group and MI group were in the Hardy-Weinberg equilibrium. The frequencies of CC, CA and AA genotype of prostacyclin synthase were 75.84%, 17.42% and 6.74% in MI group while they were 64.57%, 28.29% and 9.14% in controls respectively. There was significant difference in frequencies of CC genotype and C allele as well as CA and AA genotypes between controls and MI cases. (2)The frequencies of -765GG,-765GC and -765CC genotype of cyclooxygenase-2 were 78.65%, 19.66% and 1.69% in MI group while they were 55.43%, 34.86% and 9.71% in controls respectively. There was significant difference in frequencies of three genotypes and alleles between the two groups (P＜0.05 or P＜0.01 ). (3) In combined genotype analysis, the genotype of PGIS CC + COX-2 -765GG was significantly higher in patients with MI than in control subjects (P＜0.05). The odds ratio estimated through combined analysis of the PGIS CC and COX-2 -765GG genotypes(OR=3.87) markedly increased when compared with that estimated separately from the PGIS CC ( OR=1.72 ) or COX-2 -765GG ( OR = 2.94 ) genotype. (4)There was a significant difference in serum 6-keto-PGF1α level between MI group and control group (P＜0.05 ), but there were no differences found in every genotype of PGIS and COX-2 gene (P＞0.05 ). In the cases with both COX-2 -765GG and PGIS CC genotypes, the serum 6-keto-PGF1α levels was lower than that of others (P＜0.05). Conclusion The CC genotype and C allele of prostacyclin synthase, -765GG genotype and G allele of COX-2 might serve as risk factors of MI of Uigur population in Xinjiang.Populations with both COX-2 -765GG and PGIS CC genotypes were more at risk with MI than others which might be resulted from the decreased serum 6-keto-PGF1α concentration. The -765CC genotype and C allele of COX-2 gene might have protective functions on MI among Uigur population in Xinjiang.

Objective To establish a rat model of craniocerebral blast injury caused by the shock wave of cabin explosion.Methods Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups (10 each):3g,5g,8g TNT with vest groups,5g TNT without vest group and control group.Uncased explosives of different equivalent were suspended in the cabin center.After anesthesia,with exception of control group,the rats were placed in prone position about 31 cm below the explosive,facing the explosive with or without vest.After the explosion,the survived rats were observed,serological and pathological examinations were performed at 3h,1d and 3d after the explosion.Results In terms of tissue damage and mortality,compared with the control group,no obvious injury formed in rats of the 3g TNT with vest group,and all of them survived;Rats in 5g TNT with vest group showed mild lung injury,brain tissue edema,enlarged blood vessel,patchy hemorrhage on the brain surface,and with a mortality of 30％;Rats in 8g TNT with vest group showed serious organ damage with a mortality of 80％;Rats in 5g TNT without vest group suffered from severe lung injury,almost all died right after the explosion.Therefore,rats in 5g TNT with vest group were more in line with the experimental needs.Further serum and pathologic examinations showed that the brain water content increased,the serum neuron specific enolase (NSE) and S-100β protein also increased markedly,and necrotic or apoptotic changes happened in the cortex and hippocampus neurons.Conclusion A stable animal model of craniocerebral blast injury may be established with rats in the case of chest and abdomen protected and then exposed to 5g TNT explosion in cabin.

Objective To investigate the injury characteristics of Beagle dogs after warship multi cabin explosion.Methods Forty-eight adult male Beagle dogs were placed in the simulated blast-cabin and adjacent cabin (24 each),and ammunitions respectively containing 0.75kg TNT and 3.50kg TNT were then detonated in the blast-cabin.The survival situation,fluctuation of vital signs,morphological changes of organs and the incidence of various types of injury of the dogs were observed immediately after the explosion to 24h after injury,and the neurological functions score was performed.Results Twenty dogs died immediately after the explosion,and another 9 dogs died 24h after the explosion.The total mortality was 60.42％(29/48),and the mortalities in blastcabin and adjacent cabin were 79.17％(19/24) and 41.67％(10/24),respectively.The dog's skull was penetrated by bomb fragments,and congestion and bleeding were observed in brain tissue,lung,heart,stomach,bowels,liver and kidneys.Extremities fracture,soft tissue contusions,perforation and rupture were also checked out after explosion.The fatality rate of bomb fragment injury,blast injury and combined bomb fragment-blast injury was 27.59％(8/29),17.24％(5/29) and 55.17％(16/29),respectively.Conclusions The combined bomb fragment-blast injury show high incidence and make high fatality rate and serious injury.Combatants should effectually shield themselves with occluded objects as far as possible to avoid damage and reduce fatality.The key of early treatment is to treat the multiple injuries promptly.Intravenous fluid therapy should be practiced after hemodynamic monitoring.