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目的探讨北方汉族原发肾病综合征(PNS)儿童血管紧张素原(AGT)基因M235T单核苷酸与血管紧张素转换酶(ACE)基因多态性的关系。方法研究对象为2001—2005年首都医科大学附属儿童医院住院的148例北方汉族PNS患儿及50例正常儿童,采用聚合酶链反应-限制性片段长度多态性方法检测AGT(M235T)、ACE(I/D)的多态性。结果PNS组携带ACE基因DD型、D等位基因、AGT基因MT型及同时携带D、T等位基因的频率高于正常对照组(P分别为0.004、0.032、0.036、0.004)。复发组D等位基因频率高于非复发组(P=0.000)。PNS患儿中高胆固醇+高三酰甘油(甘油三脂)血症组DD基因频率高于正常组(P=0.006)。激素耐药组DD基因频率(34.21%)高于激素敏感组(20.91%)。ACE基因的插入序列长度为289bp,存在2处单核苷酸多态性,分别为第103、151位各插入1个G。结论携带ACE基因D等位基因、AGT基因MT型、同时携带D(DD/ID)、T(MT/TT)等位基因的北方汉族儿童为PNS的易感人群。携带ACE(DD)基因PNS患儿易复发、可能易合并高胆固醇及高三酰甘油血症,可能会有激素耐药倾向。ACE基因插入序列长度及核苷酸序列与国外报道不同。     

Renin–angiotensin systems and reproduction

Calcium and vitamin D supplementation have been shown to reduce secondary hyperparathyroidism and play a role in age-related osteoporosis. In order to define the optimal regimen of calcium and vitamin D supplementation to produce the maximal inhibition of parathyroid hormone secretion ,we compared the administration of a calcium-vitamin D supplement as a single morning dose with the administration of two divided doses at 6-hour intervals. Twelve healthy male volunteers were assigned to three investigational procedures ,which were alternated at weekly intervals. After a 'blank' control procedure ,when they were not exposed to any supplements ,they received one of two calcium-vitamin D supplement regimens: either two doses of Orocal^® D3 (500 mg calcium and 400 IU vitamin D3) with a 6-hour interval between doses ,or one water-soluble effervescent powder pack of Cacit^® vitamin D3 ,taken in the morning (1000 mg calcium and 880 IU vitamin D3). During the three procedures (control and the two calcium-vitamin D supplementation protocols) ,veinous blood was drawn every 60 minutes for up to 9 hours ,for serum calcium and parathyroid hormone measurements. The order of administration of the two calcium and vitamin D supplementation regimens was allocated by randomization. No significant changes in serum calcium were observed during the study. During the first 6 hours following calcium-vitamin D supplementation ,a statistically significant decrease in serum parathyroid hormone was observed with both regimens ,compared with baseline and the control procedure. During this first period ,no differences were observed between the two treatment regimens. However ,between the 6th and the 9th hour ,serum parathyroid hormone levels remained significantly decreased compared to baseline with the twice-daily Orocal D3 administration ,while they returned to baseline values with the once-daily Cacit D3 preparation. During this period ,the percentage decrease in serum parathyroid hormone relative to baseline was significantly greater with Orocal D3 than Cacit D3 (p = 0.0021). We therefore conclude that the twice-daily administration of 500 mg calcium and 400 IU vitamin D3 at 6-hour intervals provides a more prolonged decrease in serum parathyroid hormone levels than the administration of the same total amount of calcium and vitamin D ,as a single morning dose in young healthy volunteers. These results might have implications in terms of protection of the skeleton against secondary hyperparathyroidism and increased bone resorption and turnover in elderly subjects.     

血管紧张素原基因M235T多态性对NIDDM患者发生高血压的影响

目的 研究血管紧张素原（ＡＧＴ）基因Ｍ２３５Ｔ多态性对ＮＩＤＤＭ患者发生高血压的影响。方法 用限制性普分析法检查ＡＧＴ基因Ｍ２３５Ｔ多态性Ｍ２３５和Ｔ２３５的频率和ＴＴ、ＴＭ和ＭＭ基因型在正常对照组（６８例）、糖悄病非高血压组（１０４例）和糖尿病高血压组（８７例）中的分布，并检查各基因型对实验对象血压水平的影响。结果 糖尿病高血压组患者ＡＧＴ基因Ｍ２３５Ｔ多态性Ｔ２３５的频率明显高于对照组和糖尿病     

Lack of Association of the Renin-angiotensin System Genes Polymorphisms and Left Ventricular Hypertrophy in Hypertension

Objective: The aim of the present study was to determine if there is an association of different gene polymorphisms of renin-angiotensin system and left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) in St Petersburg population. Patients and methods: We examined 156 patients (the mean age 49 ±8 years) with mild-to-moderate EH recruited from the general population of the outpatient clinic. Left ventricular mass was measured by echocardiography and left ventricular mass index (LVMI) was calculated. Subjects were genotyped for I/D polymorphism of the angiotensin-converting enzyme (ACE) gene, A1166C polymorphism of renin-of the AT1 receptor gene, M235T polymorphism of angiotensinogen gene and-6G/A polymorphism of its promoter region. Results: Genotype distribution of the sample obeyed Hardy-Weinberg equilibrium and was comparable to that reported previously for hypertensive individuals. Groups of patients with II, ID and DD polymorphism of ACE gene did not differ significantly in their LVMI levels. Furthermore, neither ID ACE-gene polymorphism nor AT1-receptor gene and angiotensinogen gene polymorphism was associated with LVH. Additionally, no any significant gene-gene interactions were found to be associated with LVH in the group studied. Conclusions: In the light of these observations it seems reasonable to make a preliminary conclusion about lack of association between LVH and distinct polymorphisms of renin-angiotensin system genes in the population studied.     

Molecular methods for the study of the genetic determinants of nephropathy in type 1 (insulin-dependent) diabetes

Recently, evidence has accumulated that genetic factors may contribute to the development of diabetic nephropathy in patients with type 1 (insulin-dependent) diabetes mellitus. To identify variation at a gene locus, newly developed methods are introduced which employ denaturing gradient gel electrophoresis (DGGE) to study sequence differences in polymerase chain reaction (PCR)-amplified DNA fragments as well as in genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, we found no DNA sequence difference in the part of the angiotensinogen gene coding for angiotensin I. We did find, however, different distributions of a DNA polymorphism detected with the probe corresponding to exons 7 and 8 of the insulin receptor gene inRsaI DGGE blots in a comparison of patients with slow and fast progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiological data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected so that genetic studies will be possible.     

中国苗族人群血管紧张素原和血管紧张素转化酶基因多态性与冠心病的关系

目的 研究血管紧张素原(ACT)基因M235T分子变异和血管紧张素转化酶(ACE)基因I/D多态性与冠状动脉粥样硬化的关系.方法 采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)技术检测冠心病(CHD)组151例和正常对照组127例AGT基因多态性,采用聚合酶链反应技术检测CHD组151例和正常对照组127例ACE基因I/D多态性.结果 CHD组AGT-TT基因型频率为76.26%,显著高于对照组44.10%(P<0.01).ACE-DD基因型频率为35.10%,显著高于对照组14.96%(P<0.01).结论 在中国苗族人群中,AGT基因TT基因型和AGE基因DD基因型是CHD发病既相互独立又具有协同作用的危险因子.     

抑制NF-κB活性下调高糖培养的大鼠肾小球系膜细胞血管紧张素原表达水平

在体外原代培养的SD大鼠肾小球系膜细胞中,观察高糖培养条件下血管紧张素原(AGT)表达和血管紧张素Ⅱ(AngⅡ)水平变化,以及吡咯烷二硫代氨基甲酸酯(PDTC)的干预作用.结果 显示高糖上调ACT mRNA(0.29±0.07对0.20±0.05,P<0.05)和蛋白(0.66±0.23对0.37±0.15,P<0.05)表达以及AngⅡ分泌[(9.85+2.08对7.50±1.51)ps/ml,P<0.05]水平,PDTC通过抑制NF-κB活性下调其水平.     

血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与原发性高血压的相关性研究

目的 探讨血管紧张素原(AGT)基因启动子区A-20C和A-6G单核苷酸多态性与原发性高血压病(EH)之间的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对200例汉族高血压患者和192例汉族正常血压者的AGT基因-20A/C和-6A/G多态性进行检测,测定空腹血糖、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)等生物化学指标,分析各基因型和等位基因频率与原发性高血压的关系.结果 -20A/C各基因型及等位基因频率在高血压组及对照组间差别无统计学意义(χ2=2.226,P =0.136;χ2=1.78,P =0.182);-6A/G各基因型及等位基因频率在高血压组及对照组间差别亦无统计学意义(χ2=0.012,P =0.911;χ2=0.052,P =0.82).结论 AGT基因-20A/C和-6A/G多态性与原发性高血压发病无关.     

局部肾素与血管紧张素原mRNA在肝硬化门静脉高压症患者中的表达及其意义

目的探讨肝硬化门静脉高压症 (PH)对局部肾素血管紧张素系统 (LRAS)活性的影响。方法采用逆转录聚合酶链反应方法检测肝硬化门静脉高压症患者肝脏、脾脏动、静脉组织局部肾素与局部血管紧张素原mRNA的表达情况。结果　对照组内局部肾素mRNA在肝脏中最低(0 19± 0 12 ) ,显著低于脾脏动、静脉组织 [(0 4 5± 0 12 )及 (0 39± 0 12 ) ],P <0 0 5 ;局部血管紧张素原mRNA以肝脏最高 (0 6 4± 0 2 1) ,显著高于脾脏动、静脉组织 [(0 32± 0 15 )及 (0 4 1± 0 18) ],P <0 0 5。肝硬化门静脉高压症组肝脏、脾动脉、脾静脉局部肾素mRNA分别为 (0 78± 0 2 8)、(0 86± 0 35 )、(0 81± 0 2 2 ) ,显著高于对照组 ,P <0 0 5 ;肝硬化门静脉高压症组肝脏、脾动脉、脾静脉局部血管紧张素原mRNA量分别为 (0 96± 0 2 5 )、(0 83± 0 18)、(0 79± 0 2 3) ,亦显著高于对照组 ,P<0 0 5。结论肝硬化门静脉高压患者局部肾素与血管紧张素原mRNA表达增强 ,并可能促进肝硬化门静脉高压症时内脏血管病变的形成。     

Comparison of the impact of vaginal and oral administration of combined hormonal contraceptives on hepatic proteins sensitive to estrogen

OBJECTIVE: We evaluated the effects of a new combined hormonal contraceptive vaginal ring (CVR) delivering the nonandrogenic progestin Nestorone (NES) and ethinyl estradiol (EE) on several key estrogen-sensitive hepatic proteins that may be markers for the risk of arterial or venous disease events and on blood pressure (BP). Because the pharmacologic androgenicity of the progestin in these formulations influences the hepatic impact of EE, we selected an oral contraceptive (OC) delivering the androgenic progestin levonorgestrel (LNG) and EE as the comparator. We also investigated the effect of delivery route, which is known to modify the hepatic effects of estradiol, but has not been widely studied with EE. STUDY METHODS: Women, aged 18-34 years, with no contraindications to the use of combined OCs, were randomized to three cycles of treatment with a CVR delivering NES/EE (150/15 microg/day) or a combined OC providing LNG and EE (150/30 microg per tablet). Each cycle consisted of 21 days of active treatment, followed by 7 days without treatment. During the last weeks of the pretreatment and third treatment cycles, blood samples were obtained for determinations of plasma concentrations of angiotensinogen, an estrogen-sensitive hepatic protein, and serum concentrations of sex hormone-binding globulin (SHBG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and estrogen- and androgen-sensitive proteins. BP was also measured. RESULTS: Of 47 women randomized, 45 completed the study (CVR: 23; OC: 22). Within-group comparisons over time by repeated-measure analysis of variance demonstrated statistically significant changes over time with both treatments for all hepatic proteins (p < .02) but not for TC. The within-group effects, presented as relative percent difference [95% confidence interval (CI)], were greatest for angiotensinogen [CVR: 227% (195-262%); OC: 251.3% (218-288%)] and SHBG [CVR: 306% (237-389%); OC: 55% (30-86)]. Both treatments were associated with small changes in systolic BP and diastolic BP (DBP), but only the within-group change in DBP for the OC group was statistically significant (p = .04). Between-treatment comparisons of third treatment cycle mean values were performed by analysis of covariance (baseline values as covariate). No statistically significant between-treatment differences were found for angiotensinogen, sensitive only to estrogen, or BP. Statistically significant treatment differences were found for all estrogen- and androgen-sensitive proteins (p < or = .002) but not for TC. When presented as relative percent difference between the effects of treatment (CVR-OC/OC; 95% CI of percent difference), the difference was largest for SHBG (159% [117-210%]); smaller relative percent differences were found for HDL-C [31.9% (18.5-46.8%)], LDL-C [23.6% (33.4% to -2.4%)] and TG [39.0% (14.0-69.4%)], but not TC. CONCLUSION: Vaginal delivery of a combined hormonal contraceptive did not reduce the EE-associated changes in estrogen-sensitive hepatic proteins observed after use of a combined OC. Significant treatment differences between the NES/EE CVR and the LNG/EE OC were found for SHBG, HDL-C, LDL-C, and TG, proteins sensitive to androgen as well as estrogen. No treatment difference was observed for angiotensinogen, which is sensitive only to estrogen. The observed treatment differences were therefore most likely due to the difference in androgenicity between NES and LNG.