Systematic polymorphism discovery after genome-wide identification of potential susceptibility loci in a hereditary rodent model of human hypertension

Genetic strategies such as linkage analysis and quantitative trait locus (QTL) mapping have identified a multitude of loci implicated in the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR). While several candidate genetic regions have been identified in the SHR and its control, the Wistar-Kyoto rat (WKY), systematic follow-up of candidate identification with polymorphism discovery has not been widespread. In the current report, we develop a data-mining strategy to identify candidate genes for hypertension in the SHR, and then sequence each gene in the SHR and WKY strains. We integrate blood pressure QTL data, microarray data and data-mining methods. First, we determined the set of genes differentially expressed in SHR and WKY adrenal glands. Next, the chromosomal position of all differentially expressed genes was compared with peak marker position of all reported SHR blood pressure QTLs. We also identified the set of differentially expressed genes with the most extreme fold-change. Finally, the QTL positional candidates and the genes with extreme differential expression were proposed as candidate genes if they had biologically plausible roles in hypertensive pathology. We identified seven candidate genes that merit resequencing (catechol-O-methyltransferase [Comt], chromogranin A [Chga], dopamine beta-hydroxylase [Dbh], electron transferring flavoprotein dehydrogenase [Etfdh], endothelin receptor type B [Ednrb], neuropeptide Y [Npy] and phenylethanolamine-N-methyltransferase [Pnmt]), and then discovered polymorphism in four of these seven candidate genes. Chga is proposed as the strongest candidate for additional functional investigation. Our method for candidate gene identification is portable and can be applied to microarray data from any tissue, in any disease model with a QTL database.     

Cosegregation of Genes on Chromosome 5 with Heart Weight and Blood Pressure in Genetic Hypertension

Genetic factors may be involved in both essential hypertension and cardiac hypertrophy. To identify genes contributing to elevated for blood pressure and cardiac hypertrophy in the spontaneously hypertensive rat (SHR), we performed a cosegregation analysis between blood pressure and heart weight and microsatellite markers for the candidate gene ANF on chromosome 5 in F2 animals obtained by mating SHR with Wistar-Kyoto (WKY) rats. We found evidence for a quantitative trait locus (QTL) determining mean blood pressure on chromosome 5 between atrial natriuretic factor (ANF) and MITR-3893 loci. No evidence for a QTL influencing heart weight was found. We propose that in SHR, blood pressure and heart weight may be independently controlled by different genetic mechanisms and that a gene close to ANF locus on chromosome 5 contributes towards hypertension in these animals.     

Y-chromosome transfer induces changes in blood pressure and blood lipids in SHR

Previous studies with chromosome-Y consomic strains of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats suggest that a quantitative trait locus for blood pressure regulation exists on chromosome Y. To test this hypothesis in the SHR-Brown Norway (BN) model and to study the effects of chromosome Y on lipid and carbohydrate metabolism, we produced a new consomic strain of SHR carrying the Y chromosome transferred from the BN rat. We found that replacing the SHR Y chromosome with the BN Y chromosome resulted in significant decreases in systolic and diastolic blood pressures in the SHR.BN-Y consomic strain (P<0.05). To elicit possible dietary-induced variation in lipid and glucose metabolism between the SHR progenitor and chromosome-Y consomic strains, we fed rats a high-fructose diet for 15 days in addition to the normal diet. On the high-fructose diet, the SHR.BN-Y consomic rats exhibited significantly increased levels of serum triglycerides and decreased levels of serum HDL cholesterol versus the SHR progenitor rats. Glucose tolerance and insulin/glucose ratios, however, were similar in both strains on both normal and high-fructose diets. These findings provide direct evidence that a gene or genes on chromosome Y contribute to the pathogenesis of spontaneous hypertension in the SHR-BN model. These results also indicate that transfer of the Y chromosome from the BN rat onto the SHR background exacerbates dietary-induced dyslipidemia in SHR. Thus, genetic variation in genes on the Y chromosome may contribute to variation in blood pressure and lipid levels and may influence the risk for cardiovascular disease.     

Combined genealogical, mapping, and expression approaches to identify spontaneously hypertensive rat hypertension candidate genes

Allelic expression in genes has become recognized as a heritable trait by which phenotypes are generated. We have examined gene expression in the rat kidney using genome-wide microarray technology (Affymetrix). Gene expression was determined across 4 rat strains, 3 hypertensive spontaneously hypertensive rat (SHR) substrains (SHR-A3, SHR-B2, and SHR-C), and a normotensive strain (Wistar-Kyoto [WKY]). Expression measurements were made in multiple animals from all strains at 4 time points (4 weeks, 8 weeks, 12 weeks, and 18 weeks of age), covering the prehypertensive period in SHR (4 weeks), and the period of rapidly rising blood pressure (8 and 12 weeks) and of sustained hypertension (18 weeks). Regression analysis revealed a close relationship across all strains during the first 3 time points, after which SHR-A3 became a substantial outlier. SHR-B2 and SHR-C demonstrated a very close relationship in gene expression at all times but also showed increased differences compared with the other strains at 18 weeks of age. We identified genes that were consistently different in expression, comparing all SHR substrains at each time point with WKY. The resulting list of genes was compared with blood pressure quantitative trait loci reported for SHR to refine a number of genes consistently differentially expressed between SHR substrains and WKY, persistently differentially expressed across multiple time points, and located in SHR blood pressure-determinative regions of the genome. Genealogical relationships and SHR substrain intercrosses suggest that genes responsible for heritable hypertension in SHR are shared across SHR substrains. The present approach identifies a number of genes that may influence blood pressure in SHR by virtue of allelic effects on gene expression.     

Antihypertensive drugs inhibit hypertension-associated aortic DNA synthesis in the rat

The effect of antihypertensive drug treatment on aortic DNA synthesis was examined in rats with two-kidney, one clip renal hypertension and in spontaneously hypertensive rats (SHR). In two-kidney, one clip hypertensive rats, hypertension developed over a 2-week period. Four days after clipping the renal artery, during the onset of hypertension, there was an increase in aortic DNA synthesis. Aortic DNA synthesis was also increased 3 weeks later, when hypertension had been established. Captopril, hydralazine, and verapamil were each able to prevent the increase in aortic DNA synthesis and the rise in blood pressure when given throughout the first 5 days of the developing phase of hypertension, or when given to rats with established hypertension. Drug treatment of sham-operated rats had no significant effect on DNA synthesis, although blood pressure was decreased. There were no differences in blood pressure or aortic DNA synthesis in 4-week-old SHR, as compared with age-matched Wistar-Kyoto (WKY) controls or normal Wistar rats. At 17 weeks of age, when hypertension was established, aortic DNA synthesis was significantly enhanced in the SHR. Captopril or hydralazine treatment was able to reduce blood pressure and DNA synthesis to levels seen in the WKY. At 21 weeks of age, DNA synthesis in the SHR had declined to the same levels as in the WKY. Captopril, hydralazine, and verapamil may have a common ability to reduce intracellular calcium and therefore inhibit DNA synthesis. In support of this, ouabain treatment, which increases intracellular calcium by inhibiting the Na+-K+ pump, produced a significant increase in the rate of DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal nicotinic receptor activity in a genetic model of hypertension.

Intrathecal cytisine, a nicotinic receptor agonist, elicits greater dose-dependent increases in blood pressure, heart rate and nociceptive responses in SHR than normotensive rat strains. Similar to adult rats, cardiovascular and nociceptive responses were augmented in prehypertensive SHR than age-matched WKY. While hydralazine or captopril pretreatment significantly lowered blood pressure in both SHR and WKY rats, responses to i.t. cytisine were still greater in SHR. By contrast, i.t. cytisine elicited responses were not exaggerated in DOCA-salt hypertensive WKY rats. Pressor and irritation responses to i.t. cytisine can be divided into a transient, initial and persisting, late phases. Both are augmented in SHR. In F1 rats, only the late phase pressor and pain responses to i.t. cytisine are similar in magnitude to those observed in SHR suggesting a possible dominant trait in the SHR. Overall, our findings suggest that hyper-responsiveness in nociception and pressor activity to spinal cytisine in SHR may be pathogenetically associated, but not a consequence, of hypertension.     

SPINAL NICOTINIC RECEPTOR ACTIVITY IN A GENETIC MODEL OF HYPERTENSION

Intrathecal cytisine, a nicotinic receptor agonist, elicits greater dose-dependent increases in blood pressure, heart rate and nociceptive responses in SHR than normotensive rat strains. Similar to adult rats, cardiovascular and nociceptive responses were augmented in prehypertensive SHR than age-matched WKY. While hydralazine or captopril pretreatment significantly lowered blood pressure in both SHR and WKY rats, responses to i.t. cytisine were still greater in SHR. By contrast, i.t. cytisine elicited responses were not exaggerated in DOCA-salt hypertensive WKY rats. Pressor and irritation responses to i.t. cytisine can be divided into a transient, initial and persisting, late phases. Both are augmented in SHR. In F1 rats, only the late phase pressor and pain responses to i.t. cytisine are similar in magnitude to those observed in SHR suggesting a possible dominant trait in the SHR. Overall, our findings suggest that hyper-responsiveness in nociception and pressor activity to spinal cytisine in SHR may be pathogenetically associated, but not a consequence, of hypertension.     

Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats

The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial and coronary vascular function and structure. Twelve-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with and without 12 weeks of vasodilator antihypertensive treatment (hydralazine) were studied using an isolated perfused rat heart model. Hydralazine treatment normalized blood pressure in SHR but did not cause regression of cardiac hypertrophy (heart weight to body weight ratio of SHR + hydralazine 4.33 +/- 0.098 vs. SHR 4.66 +/- 0.091; WKY 3.21 +/- 0.092 and WKY + hydralazine 3.38 +/- 0.152; mean +/- SEM). Coronary flow reserve, elicited by adenosine vasodilation in the perfused heart, was decreased in SHR (29%) compared with WKY (105%) and WKY + hydralazine (100%) and was significantly improved in SHR + hydralazine (75%). Morphometric evaluation of perfusion-fixed coronary arteries and arterioles (30-400 microns diameter) demonstrated a significant increase in the slope of the regression line comparing the square root of medial area versus outer diameter in SHR (0.444) compared with WKY (0.335) and WKY + hydralazine (0.336, p less than 0.05). Blood vessels from SHR + hydralazine were not different from control (0.338). Cardiac oxygen consumption was decreased in SHR (10.9 +/- 0.74 mumols oxygen/min/g/60 mm Hg left ventricular pressure) compared with WKY (22.4 +/- 1.47) and WKY + hydralazine (23.4 +/- 1.90; p less than 0.01), while SHR + hydralazine was intermediate (16.0 +/- 1.60). These studies suggest that significant alterations in myocardial and coronary vascular structure and function occur in hypertension-induced cardiac hypertrophy. The coronary vasculature is responsive to blood pressure, independent of cardiac hypertrophy, although moderate coronary deficits do remain after chronic antihypertensive therapy.     

Genetic isolation of a blood pressure quantitative trait locus on chromosome 2 in the spontaneously hypertensive rat

OBJECTIVES: Total genome scans of genetically segregating populations derived from the spontaneously hypertensive rat (SHR) and other rat models of hypertension have suggested the presence of quantitative trait loci (QTL) regulating blood pressure and cardiac mass on multiple chromosomes, including chromosome 2. The objective of the current study was to directly test for the presence of a blood pressure QTL on rat chromosome 2. DESIGN: A new congenic strain was derived by replacing a segment of chromosome 2 in the SHR between D2Rat171 and D2Arb24 with the corresponding chromosome segment from the normotensive Brown Norway rat. Arterial pressures were directly monitored in conscious rats by radiotelemetry. RESULTS: We found that the SHR congenic strain (SHR-2) carrying a segment of chromosome 2 from the Brown Norway rat had significantly lower systolic and diastolic blood pressures than the SHR progenitor strain. The attenuation of hypertension in the SHR-2 congenic strain versus the SHR progenitor strain was accompanied by significant amelioration of cardiac hypertrophy. CONCLUSIONS: These findings demonstrate that gene(s) with major effects on blood pressure exist in the differential segment of chromosome 2 trapped within the new SHR.BN congenic strain.     

Exclusion of the catechol-o-methyltransferase gene from genes contributing to salt-sensitive hypertension in dahl salt-sensitive rats.

Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines. Several studies have suggested that this enzyme may play a role in blood pressure regulation. We previously reported that the expression levels of Comt mRNA in Dahl salt-sensitive (DS) rats were lower than those in Lewis (LEW) rats. However, the physiological significance of this phenomenon has not been investigated. The purpose of the present study was to evaluate the significance of lower expression of Comt in Dahl salt-sensitive hypertension. The Comt gene in DS rats has a palindromic insertion in 3'-untranslated region, which appears to be responsible for reduced mRNA stability. A genome-wide quantitative trait loci (QTL) analysis of blood pressure using 107 F2 rats indicated that a statistically significant QTL for pulse pressure was located at the Comt locus in chromosome 11. Microarray analysis confirmed that Comt was the only gene differentially expressed between DS and LEW rats in this chromosomal region. However, COMT inhibitors had no significant effects on blood pressure in either DS or LEW rats. Thus, Comt was excluded from the candidate genes contributing to salt-sensitive hypertension in DS rats. A true gene responsible for pulse pressure in this chromosome 11 region remains to be determined.     

自发性高血压大鼠FXYD5基因的实验研究

目的探讨自发性高血压大鼠新的高血压相关基因。方法从自发性高血压大鼠(Spontaneously Hypertensive Rats,SHR)和正常血压大鼠(Wistar-Kyoto,WKY)阻力血管(肠系膜动脉第二、三级分支)和肾脏组织中提取总RNA,利用含10000个大鼠基因的芯片检测两组大鼠mRNA表达水平,找出差异表达的基因,并经RT-PCR和定量RT-PCR初步筛选出高血压新的相关基因。结果从基因芯片的检测结果发现在SHR组中19个基因表达下调,另外19个基因表达上调,其中涉及细胞周期,直接参与代谢的酶,细胞信号转导及核转录因子等基因。选择部分已知的、并可能有功能的代表基因用RT-PCR验证,结果发现FXYD5基因在SHR明显下调,定量RT-PCR验证示FXYD5基因的表达水平在SHR组比WKY组明显下调14.8倍(P<0.01)。结论从基因芯片的结果证明了SHR和WKY不同的遗传异质性。FXYD家族的FXYD5可能与高血压的形成有关,深入研究FXYD5基因及其功能为进一步了解高血压病的分子机制提供新的思路和线索。     

当归对自发性高血压大鼠心肌miR-122的影响及其生物信息学分析

目的分析当归对自发性高血压大鼠心肌miR-122的影响及其生物信息学分析。方法将自发性高血压大鼠分为当归组、模型组、卡托普利组、当归+卡托普利组,同周龄的Wistar大鼠作为正常对照组,测定用药前后不同组别鼠尾动脉收缩压。分组给药4周后,取大鼠心肌组织进行miRNA表达谱的测定。结果当归可降低自发性高血压大鼠的血压水平。当归组表达上调的miRNA有13个,表达下调的miRNA有16个;卡托普利组表达上调的miRNA有15个,表达下调的miRNA有13个;当归+卡托普利组表达上调的miRNA有4个,表达下调的miRNA有21个。对在三组中都表达上调的miR-122进行生物学过程富集分析,发现与氨基酸转运相关的基因Slc7a1。通过对差异表达的miRNA进行靶基因预测,当归组有8个miRNA含有靶基因Slc7a1,卡托普利组有11个miRNA含有靶基因Slc7a1,当归+卡托普利组有6个miRNA含有靶基因Slc7a1。结论当归对自发性高血压大鼠miR-122表达产生影响,可能通过其靶基因Slc7a1影响内皮功能,进而调节血压,为进一步的研究提供了依据。     

Identification of a candidate gene responsible for the high blood pressure of spontaneously hypertensive rats.

OBJECTIVE: We have recently isolated a gene, designated as the SA gene, which is more than 10 times more abundantly expressed in the kidneys of spontaneously hypertensive rats (SHR) than in those of Wistar-Kyoto (WKY) rats. To address the issue whether the SA gene is one of the genes responsible for the hypertension of SHR, a genetic cosegregation analysis of the blood pressure values with the genotypes in an F2 rat population was undertaken in this study. METHODS AND DESIGN: Male F2 rats were bred from SHR and WKY rats. The genotypes of the SA gene of the F2 rats were determined by utilizing the StuI restriction fragment length polymorphism of the SA gene between SHR and WKY rats. The blood pressure values were determined by the tail-cuff method. The effect of the genotype of the SA gene on the blood pressure of the F2 rats was analysed by one-way analysis of variance. RESULTS AND CONCLUSION: The blood pressure of the F2 rats inheriting two SHR alleles of the SA gene was significantly higher than that of the F2 rats inheriting two WKY alleles. This indicates that the SA gene, or a gene closely linked to it, has a capacity to influence the blood pressure values of the F2 rat population. Further studies to identify functions of the SA gene products will be necessary.     

Effect of hydralazine on the mesenteric vasculature of hypertensive rats

To test whether structural alterations observed in the mesenteric vasculature of Wistar-Kyoto spontaneously hypertensive rats (SHR) were dependent on the presence of hypertension, male SHR and Wistar-Kyoto normotensive (WKY) rats were treated in utero and postnatally with hydralazine up to 28 weeks of age. Treated SHR, WKY, and untreated WKY rats had comparable blood pressures that were less than those of untreated SHR. Treatment altered the dimensions of the superior mesenteric, intermediate-sized, and small arteries of the mesenteric vasculature. In the case of the superior mesenteric artery and intermediate vessels, hydralazine treatment increased the lumen and medial cross-sectional areas of the arteries in WKY rats and slightly decreased both parameters in SHR. Within the small arteries, treatment significantly increased the lumen size in SHR but not WKY rats and had no significant effect on the media of the vessels. Despite the above alterations, the media-to-lumen cross-sectional area ratios remained significantly elevated in SHR over WKY rats in both the treated and control groups of animals within all classes of arteries. The results indicate that there is an inherent increase in the quantity of media surrounding the arteries of SHR when compared with WKY rats that cannot be abolished by normalizing the blood pressure in utero and postnatally with hydralazine treatment. In SHR, such changes persist not only in arteries that exhibit an increase in the media-to-lumen ratio before hypertension but also in the superior mesenteric artery in which an increase in the ratio occurs after hypertension development.     

Hypertension in the spontaneously hypertensive rat is linked to the Y chromosome

The objective of our study was to determine the genetic influence on blood pressure in spontaneously hypertensive rats (SHR), and normotensive Wistar-Kyoto (WKY) rats using genetic crosses. Blood pressure was measured by tail sphygmomanometry from 8 to 20 weeks of age. Blood pressure was significantly higher from 12 to 20 weeks in the male offspring derived from WKY mothers x SHR fathers as compared with male offspring derived from SHR mothers X WKY fathers (180 +/- 4 versus 160 +/- 5 mm Hg, p less than 0.01). There was no significant difference between the blood pressure of the F1 females, further supporting Y chromosome linkage and not parental imprinting. The blood pressure data from F2 males derived from reciprocal crosses of parental strains were consistent with the presence of a Y-linked locus, but not with an X-linked locus controlling blood pressure. The data strongly suggest that hypertension in the SHR has two primary components of equal magnitude, one consisting of a small number of autosomal loci with a second Y-linked component.     

HSP 70.2:新的高血压致病相关基因?

目的探讨HSP70·2基因是否是新的高血压致病相关基因。方法从13周龄的自发性高血压大鼠(SHR)和正常血压(WKY)大鼠的阻力血管(肠系膜动脉第二、三级分支)和肾脏组织中提取总RNA,与含10000个基因及EST片断的SBC-R-RC-100-13大鼠表达芯片进行杂交,找出差异表达的基因,并经RT-PCR和real-timeRT-PCR初步筛选出高血压新的相关基因。结果基因芯片在SHR组中发现19个上调基因,另外也发现19个基因表达下调,其中涉及细胞周期,直接参与代谢的酶,细胞信号转导及核转录因子等基因。RT-PCR和定量RT-PCR证实HSP70·2基因在SHR组中表达上调2·1倍(P<0·01)。结论HSP70·2基因可能和高血压相关,深入研究HSP70·2基因及其功能为进一步了解高血压病的分子机制提供新的思路和线索。     

Persistent cardiovascular effects of chronic renin-angiotensin system inhibition following withdrawal in adult spontaneously hypertensive rats

OBJECTIVES: It is generally accepted that short-term (4 weeks) inhibition of the renin-angiotensin system (RAS) of young spontaneously hypertensive rats (SHR) in their prehypertensive phase confers long-lasting protection from fully hypertensive levels in adulthood. However, there is very little data pertaining to the effects of such treatment in adult SHR with established hypertension. Therefore, we determined the relative effects of angiotensin converting enzyme (ACE) inhibition (perindopril), AT1 receptor blockade (candesartan cilexetil) and RAS-independent vasodilatation (hydralazine) and their withdrawal in adult SHR, on blood pressure measured by radiotelemetry, as well as on cardiac and vascular structure. METHODS: Adult male SHR were instrumented with radiotelemetry probes to measure blood pressure and heart rate continuously. SHR were given either vehicle, perindopril (1 mg/kg per day), candesartan cilexetil (2 mg/ kg per day) or hydralazine (30 mg/kg per day) at equieffective depressor doses for 4 weeks (treatment study). Separate groups of animals were also given identical treatments but were then monitored for a further 8 weeks after drug withdrawal (withdrawal study). An indirect in-vivo assessment of whole body vascular hypertrophy (mean arterial pressure during maximum vasoconstriction) was made during and after drug withdrawal, as was the pressor activity evoked by angiotensin I and angiotensin II. The effect of antihypertensive treatment on microalbuminuria was also assessed during and after drug withdrawal. Finally, left ventricular: body weight (Iv: bw) and mesenteric media: lumen ratios were determined either immediately after 4-week treatment (treatment study) or 8 weeks later (withdrawal study). RESULTS: Perindopril persistently lowered blood pressure in adult SHR whereas blood pressure returned to vehicle levels within approximately 4 and 15 days after withdrawal of hydralazine and candesartan cilexetil, respectively. Cardiac hypertrophy was reduced by all three treatments, but to a lesser extent by hydralazine (treatment study), and this regression of cardiac hypertrophy persisted only with both types of RAS inhibition (withdrawal study). Vascular hypertrophy, measured indirectly and directly, was also reduced by all three treatments, with perindopril and candesartan cilexetil causing hypotrophic and eutrophic remodelling, respectively (treatment study), although these changes were generally not maintained after drug withdrawal (withdrawal study). Angiotensin I-induced pressor responses were equally inhibited during treatment with either candesaran cilexetil or perindopril (and were unaffected by hydralazine) but normalized rapidly in both groups (within approximately 2-4 days) after withdrawal of RAS inhibition. In addition, there was a small age-related increase in microalbuminuria over the study period, which was not significantly affected by any treatment. CONCLUSIONS: Following 4-week treatment, candesartan cilexetil, perindopril and hydralazine caused similar antihypertensive effects; however, only perindopril persistently reduced blood pressure following drug withdrawal. Both types of RAS inhibition and hydralazine caused marked cardiac and vascular remodelling during treatment, whereas only the RAS inhibitors persistently regressed cardiac hypertrophy 8 weeks later. Collectively, these results indicate the importance of the RAS for the maintenance of hypertension and cardiovascular hypertrophy in adult SHR, as well as identifying differential effects of ACE inhibition and AT1 receptor blockade on persistent blood pressure reduction.     

乙型肝炎病毒e抗原与核心抗原调节靶基因的比较

目的利用基因表达谱芯片技术筛选、比较乙型肝炎病毒e抗原和核心抗原调节靶基因。方法利用分子生物学技术和生物信息学技术相结合,克隆HBeAg和HBcAg的编码基因,常规分子生物学技术构建相应的真核细胞表达载体pcDNA3.1-HBeAg和pcDNA3.1-HBcAg脂质体技术转染肝母细胞瘤细胞系HepG2,利用基因表达谱芯片技术筛选转染细胞的差异表达cDNA的类型。结果对于2个基因转染细胞系差异表达基因谱的分析,HBeAg和HBcAg共同上调的基因1条;HBeAg和HBcAg共同下调的基因1条;未发现HBeAg上调,而HBcAg下调;或HBeAg下调,而HBcAg上调的基因类型;还有一些靶基因,或只受到HBeAg的调节,或只受到HBcAg的调节。结论应用基因表达谱芯片技术对于HBeAg和HBcAg反式调节的靶基因进行分析,可以发现HBeAg和HBcAg可引起体内多个系统相关的基因表达改变,两者在体内所调节的基因种类方面还有很大差异。     

自发性高血压大鼠肾组织蛋白双向电泳

目的分析氯沙坦干预自发性高血压大鼠肾组织蛋白电泳结果。方法对白发性高血压大鼠和氯沙坦干预后高血压大鼠肾的蛋白质。用蛋白质组学的技术制作二维凝胶电泳图谱，利用Imagemaster2 D v5．0软件分析蛋白点。结果自发性高血压大鼠和氯沙坦干预后凝胶的平均蛋白点数分别为570±48和686±30。氯沙坦干预后有13个蛋白表达发生了显著变化，表达增强4个，表达降低4个，蛋白点消失5个。结论氯沙坦作用于高血压大鼠后，肾组织蛋白表达发生了明显变化，这些差异表达的蛋白点为进一步质谱分析奠定基础。     

三七花总皂苷对自发性高血压大鼠血压及心率的影响

目的观察三七花总皂苷对自发性高血压大鼠(SHR)血压、心率的影响。方法以SHR为研究对象,PowerLab系统记录给药前后血压及心率的变化。结果三七花总皂苷对SHR收缩压、舒张压在一定剂量有一定降低作用,对心率影响小。结论三七花总皂苷具有降低血压作用。