脑梗死患者血管紧张素原基因M235T分子变异的相关性研究

目的 探讨血管紧张素原(angiotensinogen AGT)基因M235T分子变异与中国人脑梗死(cerebralinfarction，CI)之间的关系。方法 采用聚合酶链反应(PCR)及限制性片段长度多态性分析(RFLP)法对75例CI、48例健康对照进行了AGT基因M235 T多态性检测。结果 CI组AGT基因T235等位基因频率为78．0％，235TT基因型频率为640％。与对照组(分别为604％、37．5％)比较差异具有显性(x^2=882，P=0003；x^2=8．27．P=0004)。校正了CI的几种危险因素(血总胆固醇、血糖及年龄)后，235TT基因型仍可使CI发生的危险性增加(分别为OR=3．289，P=0．036；OR=2．49，P=0．023)。结论 AGT基因235TT型可能是中国人群CI发病的独立危险因素.     

血管紧张素原基因T174M和M235T多态与原发性高血压的关系

目的　研究血管紧张素原 (AGT)基因第 2号外显子T174M和M 2 35T多态与中国汉人原发性高血压 (EH)的关系。方法　采用多重SNaPshot反应 ,在 185例EH患者 (EH组 )和 185名健康对照者 (对照组 )中 ,对T174M和M 2 35T多态进行基因分型。结果　对照组与EH组T174M和M2 35T多态的CC、CT和TT基因型分布的差异无显著性 (P值均 >0 .0 5 ) ;C、T等位基因频率的差异亦无显著性 (P值均 >0 .0 5 )。按性别进行分层 ,EH组女性的M 2 35T多态的基因型分布 (5 3、2 8、2 )与对照组女性 (37、11、6 )的差异有显著性 (χ2 =6 .4 0 3,P =0 .0 4 1)。Logistic回归分析显示 ,年龄 (β =0 .36 6 ,OR =1.4 4 2 ,95 %CI =0 .988～ 2 .10 4 ,P =0 .0 5 8)、体重指数(β =0 .2 11,OR =1.2 34,95 %CI=1.0 78～ 1.4 14 ,P =0 .0 0 2 )、三酰甘油 (β =1.70 5 ,OR =5 .5 0 1,95 %CI =2 .179～ 13.890 ,P =0 .0 0 0 )和血糖 (β =0 .74 5 ,OR =2 .10 6 ,95 %CI =1.0 4 0～ 4 .2 6 4 ,P =0 .0 39)均是EH发生的独立危险因素。结论　AGT基因M 2 35T多态可能与汉族女性EH的发病有关     

局部血管紧张素原mRNA的表达与核因子-κB的活化在门静脉高压症性血管病变中的意义

目的探讨肝硬化门静脉高压症(PHT)时局部血管紧张素原mRNA表达与核因子-κB(NF-κB)的活化在门静脉高压症性血管病变中的意义。方法采用逆转录聚合酶链反应(RT-0PCR)方法检测肝硬化门静脉高压症病人脾脏动、静脉组织和正常血管局部血管紧张素原mRNA的表达情况,用化学发光凝胶电泳迁移率实验(EMSA)方法检测局部NF-κB的活性。结果对照组内脾脏动、静脉组织局部血管紧张素原mRNA分别为0.23±0.12、0.18±0.10,显著低于肝硬化门静脉高压症组脾动脉、脾静脉组织局部血管紧张素原mRNA的表达0.48±0.21、0.43±0.16(P<0.05);对照组脾动、静脉局部NF-κB未被检测到明显的活性,而于肝硬化门静脉高压症组检测到显著具有活性的NF-κB表达(P<0.05)。结论肝硬化门静脉高压病人局部血管紧张素原mRNA表达增强,NF-κB的活化,可能是肝硬化门静脉高压症时内脏血管病变形成和发展的原因之一。     

Antidiuretic hormone and renin in rats with diabetes insipidus

Administration of antidiuretic hormone to rats at a dose of 400 or 40 mu/100 g i.m. caused a significant fall in plasma renin concentration. (PRC). In male rats with diabetes insipidus, a significant elevation of both plasma and kidney renin concentrations was not significantly different from that in control female rats. Ovariectomy did not abolish this difference between female and male rats with hereditary diabetes insipidus. Plasma angiotensinogen (renin substrate) was significantly higher in male rats compared to females but no difference between rats with and without diabetes insipidus was observed.     

血管紧张素原基因M235T多态性与脑梗死的相关性研究

目的　探讨血管紧张素原 (angiotensinogen AGT)基因 M2 35 T多态性与中国人脑梗死 (CI)之间的关系。方法　采用聚合酶链反应 (PCR)及限制性片段长度多态性分析 (RFL P)法对 75例 CI、48例健康对照者进行了 AGT基因 M2 35 T多态性检测。结果　 CI组 AGT基因 T2 35等位基因频率为 0 .78,2 35 TT基因型频率为 0 .6 4,与对照组 (分别为 0 .6 0 4和 0 .375 )比较差异具有显著性 (χ2 =8.82 P<0 .0 0 5 ;χ2 =8.2 7P<0 .0 0 5 )。校正了 CI的几种危险因素 (血总胆固醇、血糖及年龄 )后 ,2 35 TT基因型仍可使 CI发生的危险性增加 (分别为 OR=3.2 89,P<0 .0 5 ;OR=2 .49,P<0 .0 5 )。结论　 AGT基因 2 35 TT型可能是中国人群 CI发病的独立危险因素。     

Urinary angiotensinogen excretion is associated with blood pressure in obese young adults

Intrarenal RAS has been suggested to be involved in the pathogenesis of hypertension. It was recently reported that urinary angiotensinogen excretion levels are associated with intrarenal RAS. However, few markers predicting intrarenal RAS have been investigated in obese young subjects. The present study evaluated the association between blood pressure and intrarenal RAS activity, inflammation and oxidative stress in obese young adults. Urinary angiotensinogen excretion and urinary monocyte chemotactic protein (MCP)-1, and urinary thiobarbituric acid reaction substance (TBARS) as markers of intrarenal RAS activity, inflammation, and oxidative stress, respectively, were determined from morning urine of 111 young male adults. Participants were divided into two groups based on the body mass index (BMI). Natural log-transformed urinary angiotensinogen excretion level was significantly associated with blood pressure, MCP-1 excretion, and TBARS excretion elevation in the obese group (BMI ≥25?kg/m²). Multivariable analyses showed that every 1 standard deviation increase in natural-log transformed urinary angiotensinogen and MCP-1 excretion, but not TBARS excretion level was associated with elevated blood pressure in the obese group. These results indicate that urinary angiotensinogen and MCP-1 excretion were associated with blood pressure elevation in this population of obese young adults. It suggested that inappropriate RAS activity and inflammation precedes hypertension in obese young subjects and urinary angiotensinogen could be a screening maker for hypertension in young obese subjects.     

Role of the local renin-angiotensin system in cardiac damage: a minireview focussing on transgenic animal models

The local generation of all components of the renin-angiotensin system (RAS) in the heart has been the basis for the postulation of a tissue RAS in this organ. Since angiotensin II is involved in the induction of cardiac hypertrophy and fibrosis the local generation of this peptide may be of highest clinical importance. Several transgenic animal models have been generated to evaluate the functional importance of the cardiac RAS. We have established a new hypertensive mouse model lacking local angiotensinogen expression in the heart. In these animals, cardiac weight and collagen synthesis are increased compared to normotensive control mice but to a lesser extent than in mice with equally enhanced blood pressure but intact cardiac angiotensinogen generation. Thus, we have shown that local synthesis of this protein is involved but not essential in the development of cardiac hypertrophy and fibrosis.     

心肌梗死患者血管紧张素原基因多态性临床检测意义的研究

目的 探讨血管紧张素原基因（AGT）在人群中的分布、临床常见生化指标与心肌梗死的关系。方法 选取患者组114例及对照组204例，用聚合酶链反应（PCR）、限制性片段长度多态性（RFLP）分析，对群体患者和群体健康对照组进行基因分型，统计分析。结果 ACT基因型频率及等位基因频率分布比较均匀；心肌梗死发生与性别、年龄无特异相关性。174MM型和M174等位基因的频率患者组显著高于健康对照组，携带突变型MM基因型的个体比野生型TT者患心肌梗死的危险性高5．667倍，基因突变与心肌梗死发生相关。其他因素中只有吸烟与否其P值〈0．001。校正主要危险因素后，MM基因型仍与心肌梗死发病显著相关，调整后P值分别为0．043和0．001。结论 AGT基因基因型及等位基因在群体中的分布无年龄、性别差异，MM基因型与心肌梗死有关。     

Stretch-induced regulation of angiotensinogen gene expression in cardiac myocytes and fibroblasts: opposing roles of JNK1/2 and p38alpha MAP kinases

The cardiac renin-angiotensin system (RAS) has been implicated in mediating myocyte hypertrophy, remodeling, and fibroblast proliferation in the hemodynamically overloaded heart. However, the intracellular signaling mechanisms responsible for regulation of angiotensinogen (Ao), a substrate of the RAS system, are largely unknown. Here we report the identification of JNK1/2 as a negative, and p38α as a major positive regulator of Ao gene expression. Isolated neonatal rat ventricular myocytes (NRVM) and fibroblasts (NRFB) plated on deformable membranes coated with collagen IV, were exposed to 20% equiaxial static-stretch (0-24 h). Mechanical stretch initially depressed Ao gene expression (4 h), whereas after 8 h, Ao gene expression increased in a time-dependent manner. Blockade of JNK1/2 with SP600125 increased basal Ao gene expression in NRVM (10.52 ± 1.98 fold, P < 0.001) and NRFB (13.32 ± 2.07 fold, P < 0.001). Adenovirus-mediated expression of wild-type JNK1 significantly inhibited, whereas expression of dominant-negative JNK1 and JNK2 increased basal and stretch-mediated (24 h) Ao gene expression, showing both JNK1 and JNK2 to be negative regulators of Ao gene expression in NRVM and NRFB. Blockade of p38α/β by SB202190 or p38α by SB203580 significantly inhibited stretch-induced (24 h) Ao gene expression, whereas expression of wild-type p38α increased stretch-induced Ao gene expression in both NRVM (8.41 ± 1.50 fold, P < 0.001) and NRFB (3.39 ± 0.74 fold, P < 0.001). Conversely, expression of dominant-negative p38α significantly inhibited stretch response. Moreover, expression of constitutively active MKK6b (E) significantly stimulated Ao gene expression in the absence of stretch, indicating that p38 activation alone is sufficient to induce Ao gene expression. Taken together p38α was demonstrated to be a positive regulator, whereas JNK1/2 was found to be a negative regulator of Ao gene expression. Prolonged stretch diminished JNK1/2 activation, which was accompanied by a reciprocal increase in p38 activation and Ao gene expression. This suggests that a balance in JNK1/2 and p38α activation determines the level of Ao gene expression in myocardial cells.     

血管紧张素原基因多态性与血管性认知障碍关系的研究

目的 探讨血管紧张素原(AGT)基因G-6A和M235T多态性与血管性认知障碍(VCI)的关系.方法 采用随机对照研究,聚合酶链反应(PCR)方法检测VCI组(67例)、正常对照组(71例)AGT基因G-6A和M235T多态性.结果 VCI组AGT基因M235TT等位基因频率0.73,TT基因型频率0.52,与对照组(0.68,0.45)比较差异无统计学意义(P0.05),TT基因型对VCI的比数比为0.544(95%CI为0.208～1.424,P0.05).VCI组AGT基因G-6 A等位基因频率0.69,AA基因型频率0.48,与对照组(0.63,0.39)比较差异无统计学意义(P0.05),AA基因型对VCI的比数比为0.602(95%CI为0.252～1.738.P0.05).结论 脑梗死伴血管性认知障碍患者与AGT基因G-6A和M235T多态性无关,AGT基因这两个位点多态性未参与发病.