血管紧张素转化酶基因多态性与其血清水平及老年高血压病的关系

目的探讨中国人群中血管紧张素转化酶(ACE)基因的插入/缺失(I/D)多态性与其血清水平及老年高血压病之间的关系。方法应用多聚酶链反应(PCR)方法检测ACE基因多态性,同时测定血清ACE水平,对56例老年高血压病患者与40例老年健康对照者进行比较分析。结果老年高血压组D等位基因频率显著高于对照组(0.61vs0.46,P<0.05),血清ACE水平亦显著高于对照组［(31.0±11.1)U/Lvs(25.1±10.0)U/L,P<0.05］。血清ACE水平依次为DD型>ID型>II型。DD型与ID型及DD型与II型之间均具有显著差异。结论ACE基因多态性与血清ACE水平有关,DD基因型者血清ACE水平显著升高,D等位基因可能是老年高血压发病的遗传学基础之一。     

血管紧张素转换酶基因多态性与培垛普利对高血压患者内皮舒张功能障碍的干预作用

目的 探讨培垛普利对高血压患者肱动脉内皮舒张功能障碍的干预作用以及血管紧张素转换酶（ACE）基因的插入／缺失（I／D）多态性对这种干预作用的影响。方法 以87名无合并症的老年原发性高血压患者（高血压组）和50名正常老年人（对照组）作为研究对象，用高分辨超声技术检测研究对象的肱动脉内皮舒张功能，用聚合酶链反应（PCR）方法检测研究对象的ACE基因I／D多态性。高血压组在接受培垛普利治疗12周后复测肱动脉内皮舒张功能。结果 高血压组三个基因型亚组的内皮依赖舒张功能与对照组对应的三个基因型亚组比较均有显著减退（P〈0．01）。无论是高血压组还是对照组，具有DD基因型个体的肱动脉内皮依赖舒张功能均显著低于II型个体（P〈0．05）。在高血压组，培垛普利治疗后三个基因型亚组的肱动脉内皮依赖舒张功能与治疗前比较均有显著改善（P〈0．01），改善幅度DD〉ID〉II型，DD型或ID型与II型亚组比较差异有统计学意义（P〈0．01）。结论 培垛普利能逆转老年高血压患者的肱动脉内皮依赖舒张功能障碍，含有D等位基因的患者获益更大。     

血管紧张素转换酶基因多态性与脑梗死危险因素的关系

目的：探讨血管紧张素转换酶（ACE）基因多态性与中国汉族人脑梗死危险因素关系。方法：应用聚合酶链反应（PCR）,测定165例脑梗死、101例高血压患者和106例正常对照者ACE基因插入／缺失（I／D）多态性,用比色法测定血清ACE水平,并调查脑梗死经典的危险因素,结果：脑梗死组DD型基因频率为0．43,高于高血压组的0．31(X^2=4．03,P＜0．05）和正常对照组的0．17（X^2=19．86,P＜0．01）,且D等位基因亦明显高于高血压组和正常对照组（X^2=18．30,12．41、29．00、12．10,P＜0．01）。脑梗死组血清ACE水平明显高于正常对照组（F＝2240．06,P＜0．01）其中DD基因型血清ACE水平又高于同组DI基因和Ⅱ基因（F＝8．83,P＜0．01）。结论：ACE基因缺失多态性可能是中国人汉族脑梗死独立危险因素,循环ACE活性与基因缺失多态性相关。     

血管紧张素转换酶基因型多态性与妊娠期肝内胆汁淤积症相关性

目的:探讨血管紧张素转换酶(ACE)基因多态性与妊娠期肝内胆汁淤积症(ICP)的关系。方法:应用聚合酶链反应技术(PCR)检测ICP孕妇与正常孕妇ACE基因插入/缺失多态性,测定并比较ICP组不同ACE基因型肝功能指标水平,分析ACE基因型和等位基因与ICP孕妇肝功能水平的相关关系。结果:ICP组ACE基因插入/缺失DD、ID、II基因型频率分别为16.42%、55.22%、28.36%,与对照组比较差异有统计学意义(P0.05)。ACE/DD基因型在高胆红素组表达明显增高(P0.05),DD基因型患者比ID、II基因型患者血清胆红素水平升高。结论:ACE基因I/D多态性与ICP存在相关性,具有DD基因型的妇女有高度的ICP易感性,携带D等位基因可能增加ICP的患病风险。D等位基因和DD基因型可能通过影响肝脏排泄来影响ICP发病和发展。     

ACE基因多态性与T2DM患者股动脉内中膜厚度的关系

目的 探讨人类血管紧张素转换酶（ACE）基因插入/缺失多态性（I/D）与2型糖尿病（T2DM）患者股动脉内中膜厚度（FA-IMT）的关系。方法 采用限制性片段长度多形态多聚酶链式反应（PCR-RFLP）技术检测了303例T2DM患者和93例健康个体ACE基因内含子16插入/缺失（I/D）多态性，利用B型超声检测T2DM患者FA-IMT的情况。结果与健康对照组比较，T2DM患者Ⅰ等位基因频率显著增高，而D等位基因频率显著降低。携带ACEDD基因型者FA-IMT增厚的比例显著高于携带Ⅱ及ID基因型者（P〈0．01）；多元线性逐步回归分析显示，与T2DM患者基线FA-IMT关系密切的指标为年龄、ACEDD基因型、饮酒史。结论 ACEDD基因型是他DM患者FA-IMT增加的独立的危险因素。     

我国汉族人群血管紧张素转换酶基因多态性与原发性高血压关系的Meta分析

[目的]探讨我国汉族人群血管紧张素转换酶(ACE)基因多态性与原发性高血压(EH)的关系。[方法]应用Meta分析方法对国内有关汉族人群共计1678名原发性高血压患者和1630名正常对照的ACE基因多态性与原发性高血压关系的15个研究结果进行综合定量分析。用随机效应模型(D-L法),计算合并比值比OR及其95%的可信区间(95%CI)。[结果]基因型DD(/ID,II)、等位基因(D/I)分布的合并OR分别为1.78(95%CI:1.30~2.78)和1.24(95%CI:1.03~1.49)。[结论]我国汉族人群中带有DD基因型以及D对位基因的个体容易患原发性高血压。     

血管紧张素转换酶基因多态性与高血压脑梗死的关系

目的研究血管紧张素转换酶（angiotensin convening enzyme,ACE）基因多态性与高血压脑梗死之间的相关关系及可能机制。方法对52例高血压脑梗死和70例健康对照者用聚合酶链反应（polymerasechainreaction,PCR）技术和琼脂糖凝胶电泳法分别进行ACE基因插入／缺失（Insertion／Deletion,L/D）多态性测定。分析比较高血压脑梗死组与对照组之间ACE基因多态性的分布差异。结果高血压脑梗死组DD基因型和D等位基因频率分别为32．7％、53．8％,与对照组比较明显增高,且差异有统计学意义（P〈0．05）。结论ACE基因多态性与合并高血压的脑梗死有关,可增加高血压脑梗死的发病危险。     

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19.The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0).We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331–4.609).These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.     

原发性高血压患者中血管紧张素转换酶2基因单核苷酸多态性与缬沙坦降压疗效的相关性研究

目的探讨原发性高血压患者中血管紧张素转换酶2基因单核苷酸多态性与原发性高血压发生及缬沙坦治疗的疗效关系。方法应用直接测序方法对120例原发性高血压和60例正常人群中血管紧张素转换酶2（ACE2）基因作SNP分型。结果男、女原发性高血压患者G8790A位点上G等位基因频率和正常人群中相比有统计学意义（X2=5．310,4．423,P〈0．05）;其与用药前、后血压的变化无统计学意义（P〉0．05）。结论血管紧张素转换酶2基因的A1675G单核苷酸多态性与原发性高血压发病有关,携带G等位基因人群发生高血压的危险性相对较大,ACE2可作为原发性高血压的候选易感基因。     

高血压合并左心室肥厚患者血管紧张素转化酶基因多态性研究

目的探讨血管紧张素转换酶(ACE)基因多态性与高血压合并左心室肥厚(LVH)的关系。方法应用聚合酶链反应(PCR)技术对150名健康人(normotensivecontrols,NT)与152例原发性高血压病无合并症患者及80例高血压合并左心室肥厚患者ACEI/D基因多态性进行检测;利用超声心动图检测左心室质量(LVM)并计算左心室质量指数(LVMI)。结果原发性高血压非肥厚组及左心室肥厚组的ACE基因的D等位基因的频率为0.493及0.514,显著高于对照组的0.333(P<0.05)。结论ACE基因缺失多态性可能是高血压合并LVH易患性的危险因子。     

茶多酚对D-半乳糖诱致大鼠眼晶状体损伤的干预作用及其机制

目的探讨茶多酚对D-半乳糖诱致大鼠眼晶体损伤的干预作用及其机制。方法D-半乳糖(400mg/kg bw)腹腔注射给药,2w后模型大鼠同时给予氨基胍(75mg/kg bw)和茶多酚高、中、低(150、75、37.5mg/kg bw)剂量处理至第14w。处理动物并取血测定红细胞醛糖还原酶(AR)活性、糖化血红蛋白、血清果糖胺(FRA)和晚期血浆糖基化终末产物(AGEs)含量;取眼晶状体测定AR、GR、SOD和SDH活性,测定AGEs、GSH、MDA含量和乳酸脱氢酶(LDH)漏出量,流式细胞术检测晶状体上皮细胞凋亡情况,透射电镜观察晶状体上皮细胞超微结构的变化。结果D-半乳糖处理动物14w后,体内糖化血红蛋白、血清果糖胺、AGEs水平和AR活性明显升高,并伴有眼晶状体AGEs含量和AR活性的增加,抗氧化酶活性降低,氧化产物增加,晶状体上皮细胞出现凋亡及细胞核和线粒体结构的损伤。茶多酚处理12w后,明显降低动物体内红细胞和晶体AR活性,降低糖化血红蛋白、血清果糖胺和AGEs含量,降低晶状体AGEs、MDA含量和LDH释放量,提高GR、SDH和SOD活性,并降低晶状体上皮细胞凋亡率,减少细胞核和线粒体结构损伤的程度。结论D-半乳糖可诱致大鼠全身和眼晶状体糖基化和氧化应激性损伤,导致眼晶体细胞核和线粒体结构改变,诱导细胞凋亡,茶多酚可能通过抑制糖基化和氧化应激反应,对其损伤提供保护作用。     

Associations between RAS Gene Polymorphisms, Environmental Factors and Hypertension in Mongolian People

Objective: To explore the association between RAS system genes (AGT, ACE and AT₁R) polymorphisms, environmental factors and hypertension in Mongolian people. Methods: On the basis of cross-sectional study, a case–control study with 299 hypertensives and 281 nomotensives was conducted, and the conditions of environmental factors were acquired by questionnaire. Serum lipid and insulin were detected by using biochemical experiments. Six single nucleotide polymorphisms of RAS system were genotyped by polymerase chain reaction/restriction fragment length polymorphism and polymerase chain reaction/single strand conformation polymorphism. Results: Overweight or obesity, high serum TG and insulin resistance were risk factors of hypertension by single factor analysis. All the RAS genotype distributions were compatible with Hardy–Weinberg expectations. There were no significant differences to be found between cases and controls for genotype frequencies or allele frequencies of the six polymorphisms of RAS system, except in men group, OR value of men carried ACE ID+DD genotype vs. men carried II genotype was 2.20 (95%CI 1.21–4.02), and OR of people who carried both ACE ID (or DD) and AGT M235T MT (or MM) vs. people with both ACE ID (or DD) and AGT M235T TT was 1.59 (95%CI 1.06–2.38). Conclusions: Overweight or obesity, dyslipidemia and insulin resistance were risk factors of hypertension in Mongolian people. ACE gene ID+DD genotype was the risk factor of hypertension in men group. People who carried both ACE ID (or DD) and AGT M235T MT (or MM) had more risk to have hypertension.     

ACE、AT_1R、eNOS基因多态性与重度子痫前期的相关性

目的:探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性、血管紧张素Ⅱ受体Ⅰ(AT1R)基因A1166C多态性和内皮细胞一氧化氮合成酶(eNOS)基因G894T多态性与重度子痫前期发病的关系。方法:应用荧光定量PCR、DNA测序技术检测50例重度子痫前期患者(病例组)与100例正常妊娠妇女(对照组)ACE、AT1R、eNOS基因多态性。结果:病例组ACE基因ID基因型频率(32.0%)显著低于对照组(57.0%,P0.01),DD基因型频率(40.0%)显著高于对照组(20.0%,P0.01);病例组AT1R基因AA基因型频率(78.0%)显著低于对照组(94.0%,P0.01),AC基因型频率(22.0%)显著高于对照组(5.0%,P0.01);相对于AA基因型,携带AC基因型者的OR值为5.303,病例组C等位基因频率(11.0%)显著高于对照组(3.5%,P0.05),相对于A等位基因,携带C等位基因者OR值为3.408;两组eNOS基因各基因型与等位基因频率差异无统计学意义;联合基因型无统计学意义。结论:ACE基因I/D多态性和AT1R基因A1166C多态性与重度子痫前期的发病有关,未发现eNOS基因G894T多态性与重度子痫前期的发病有关,未发现基因间有协同作用。     

血脂与ACE基因多态性对糖尿病肾病交互作用

目的探讨血管紧张素Ⅰ转换酶（ACE）基因的插入／缺失多态性与高血脂因素对糖尿病肾病发生的交互作用及其强度。方法采用聚合酶链反应技术检测109例2型糖尿病（T2MD）患者（其中合并肾病患者37例。未发生肾病患者72例）ACE基因插入／缺失多态性，用相加模型分析其与高血脂对糖尿病合并肾病的交互作用。结果糖尿病肾病患者的DD基因型频率高于无肾病糖尿病患者组（75．7％和55．6％，P=0．040），D等位基因频率也有升高的趋势，差异接近显著性水准（87．8％和77．1％，P=0．057）。肾病组甘油三酯水平高于单纯糖尿病组，差异有统计学意义（P=0．049）。ACE基因DD基因型与血脂对糖尿病肾病发生有明显正交互作用，与总胆固醇、甘油三酯的交互作用系数分别为2．17，4．29，归因交互百分比分别为42．03％，62．60％，OR（AB）值分别为4．52和10．75。结论ACE基因的DD基因型可能增高2型糖尿病患者并发肾病的易感性，并且与高总胆固醇、高甘油三酯有交互作用。     

The Nutraceutical Antihypertensive Action of C-Phycocyanin in Chronic Kidney Disease Is Related to the Prevention of Endothelial Dysfunction

C-phycocyanin (CPC) is an antihypertensive that is not still wholly pharmacologically described. The aim of this study was to evaluate whether CPC counteracts endothelial dysfunction as an antihypertensive mechanism in rats with 5/6 nephrectomy (NFx) as a chronic kidney disease (CKD) model. Twenty-four male Wistar rats were divided into four groups: sham control, sham-treated with CPC (100 mg/Kg/d), NFx, and NFx treated with CPC. Blood pressure was measured each week, and renal function evaluated at the end of the treatment. Afterward, animals were euthanized, and their thoracic aortas were analyzed for endothelium functional test, oxidative stress, and NO production. 5/6 Nephrectomy caused hypertension increasing lipid peroxidation and ROS production, overexpression of inducible nitric oxide synthase (iNOS), reduction in the first-line antioxidant enzymes activities, and reduced-glutathione (GSH) with a down-expression of eNOS. The vasomotor response reduced endothelium-dependent vasodilation in aorta segments exposed to acetylcholine and sodium nitroprusside. However, the treatment with CPC prevented hypertension by reducing oxidative stress, NO system disturbance, and endothelial dysfunction. The CPC treatment did not prevent CKD-caused disturbance in the antioxidant enzymes activities. Therefore, CPC exhibited an antihypertensive activity while avoiding endothelial dysfunction.     

Distinct Impact of Natural Sugars from Fruit Juices and Added Sugars on Caloric Intake,Body Weight,Glycaemia, Oxidative Stress and Glycation in Diabetic Rats

Although fruit juices are a natural source of sugars, there is a controversy whether their sugar content has similar harmful effects as beverages’ added-sugars. We aimed to study the role of fruit juice sugars in inducing overweight, hyperglycaemia, glycation and oxidative stress in normal and diabetic animal models. In diabetic Goto-Kakizaki (GK) rats, we compared the effects of four different fruit juices (4-weeks) with sugary solutions having a similar sugar profile and concentration. In vitro, the sugary solutions were more susceptible to AGE formation than fruit juices, also causing higher postprandial glycaemia and lower erythrocytes’ antioxidant capacity in vivo (single intake). In GK rats, ad libitum fruit juice consumption (4-weeks) did not change body weight, glycaemia, oxidative stress nor glycation. Consumption of a matched volume of sugary solutions aggravated fasting glycaemia but had a moderate impact on caloric intake and oxidative stress/glycation markers in tissues of diabetic rats. Ad libitum availability of the same sugary solutions impaired energy balance regulation, leading to higher caloric intake than ad libitum fruit juices and controls, as well as weight gain, fasting hyperglycaemia, insulin intolerance and impaired oxidative stress/glycation markers in several tissues. We demonstrated the distinct role of sugars naturally present in fruit juices and added sugars in energy balance regulation, impairing oxidative stress, glycation and glucose metabolism in an animal model of type 2 diabetes.     

Beneficial effect of low ethanol intake on the cardiovascular system: possible biochemical mechanisms

Low ethanol intake is known to have a beneficial effect on cardiovascular disease. In cardiovascular disease, insulin resistance leads to altered glucose and lipid metabolism resulting in an increased production of aldehydes, including methylglyoxal. Aldehydes react non-enzymatically with sulfhydryl and amino groups of proteins forming advanced glycation end products (AGEs), altering protein structure and function. These alterations cause endothelial dysfunction with increased cytosolic free calcium, peripheral vascular resistance, and blood pressure. AGEs produce atherogenic effects including oxidative stress, platelet adhesion, inflammation, smooth muscle cell proliferation and modification of lipoproteins. Low ethanol intake attenuates hypertension and atherosclerosis but the mechanism of this effect is not clear. Ethanol at low concentrations is metabolized by low Km alcohol dehydrogenase and aldehyde dehydrogenase, both reactions resulting in the production of reduced nicotinamide adenine dinucleotide (NADH). This creates a reductive environment, decreasing oxidative stress and secondary production of aldehydes through lipid peroxidation. NADH may also increase the tissue levels of the antioxidants cysteine and glutathione, which bind aldehydes and stimulate methylglyoxal catabolism. Low ethanol improves insulin resistance, increases high-density lipoprotein and stimulates activity of the antioxidant enzyme, paraoxonase. In conclusion, we suggest that chronic low ethanol intake confers its beneficial effect mainly through its ability to increase antioxidant capacity and lower AGEs.     

ACE基因多态性与煤矿井下工人原发性高血压的关系

目的分析血管紧张素转换酶(ACE)基因多态性与原发性高血压(EH)的关系。方法选择煤矿井下接尘工人为研究对象(EH组和对照组各206人),进行职业流行病学调查,并收集研究对象空腹静脉血5 ml,酚氯仿法提取基因组DNA,采用聚合酶链反应(PCR)方法检测ACE基因多态性。比较两组间的基因型、等位基因频率及倒班分布的差异。结果 EH组和对照组倒班作业工人所占的比例分别为42.23%和29.61%,组间分布比较差异有统计学意义(χ2=7.13,P<0.05),EH发生的危险增加了1.74倍。ACE基因II、ID、DD基因型和等位基因I、D的分布,差异无统计学意义(P>0.05),提示ACE基因多态性与EH无直接关系;但倒班与I和D等位基因联合作用的OR值分别为1.86(OR95%CI:1.32～2.63)和1.72(OR95%CI:1.09～2.71),相乘模型交互作用产生的OReg值为0.79,提示倒班与ACE基因I/D等位基因之间存在负交互作用(似然比检验P<0.05)。结论倒班可能是EH的危险因素且可能与ACE基因插入/缺失序列等位基因存在交互作用。     

Role and Treatment of Insulin Resistance in Patients with Chronic Kidney Disease: A Review

Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.     

The ACE inhibitory dipeptide Met-Tyr diminishes free radical formation in human endothelial cells via induction of heme oxygenase-1 and ferritin

Food sources such as soybeans and fish contain angiotensin I converting enzyme (ACE) inhibitory peptides with antihypertensive properties. Methionine-tyrosine (Met-Tyr) is an ACE inhibitory dipeptide derived from sardine muscle. The present study investigates the effect of Met-Tyr on the expression of the antioxidant stress proteins, heme oxygenase-1 (HO-1) and ferritin, in endothelial cells derived from the human umbilical vein and their contribution to the decrease in radical formation that occurs under the influence of this dipeptide. Preincubation of endothelial cells with Met-Tyr (10-300 micromol/L) followed by washout markedly diminished subsequently induced NADPH-mediated radical formation. This indirect protection was associated with a significant increase in protein expression of HO-1 and ferritin and abolished by the HO inhibitor zinc deuteroporphyrin IX 2,4-bis-ethylene glycol (ZnBG). The HO product bilirubin produced antioxidant effects comparable to those of Met-Tyr. Met-Tyr raised HO-1 mRNA levels by enhancing mRNA stability. Antioxidant effects were specific for Met-Tyr and not observed with other methionine-containing dipeptides or ACE inhibitory agents. Our results demonstrate that Met-Tyr protects endothelial cells from oxidative stress via induction of HO-1 and ferritin but independently of its ACE inhibitory properties. This pathway represents a novel, potentially antiatherogenic mechanism of Met-Tyr and dietary proteins releasing Met-Tyr during gastrointestinal digestion.