肽基二肽酶A

摘要： 2019冠状病毒病(COVID-19)暴发是国际关注的突发公共卫生事件,COVID-19常导致严重的呼吸衰竭,部分患者会出现急性心肌损伤和高血压等心血管疾病,且COVID-19与病毒受体血管紧张素转换酶2(ACE2)密切相关。本文就COVID-19相关心血管疾病发病率、ACE2介导的相关作用机制及最新的诊治方法作一综述。

摘要： 肾素-血管紧张素系统(RAS)具有维持心血管稳态、水电解质平衡的作用,这一过程中血管紧张素转化酶Ⅱ(ACE2)及其作用轴血管紧张素1-7[Ang-(1-7)]和Mas受体(MasR)共同组成的ACE2-Ang-(1-7)-MasR轴广泛参与中枢神经系统疾病的病理生理学过程。本文总结RAS结构与功能以及ACE2-Ang-(1-7)-MasR轴在缺血性卒中、认知功能障碍、焦虑状态、神经系统变性疾病发病机制中的作用进展,以期提高研究人员和临床医师对ACE2-Ang-(1-7)-MasR轴的认识,为药物研发提供新靶点。

摘要： 新型冠状病毒(SARS-CoV-2)可通过血管紧张素转换酶2(ACE2)入侵靶器官,ACE2高表达的肺上皮细胞可能是SARS-CoV-2主要感染的靶细胞.然而,除呼吸道症状外,有些患者也表现出非呼吸系统症状,如肾功能衰竭,这意味着SARS-CoV-2可能侵犯了其他器官.而肾小管表达相对较高的ACE2,表明肾脏近端小管细胞可能是SARS-CoV-2的易感细胞.结合现有文献,该文介绍了SARS-CoV-2导致肾脏损伤可能的病理生理机制及潜在的有效治疗手段.

摘要： 2019新型冠状病毒导致的新型冠状病毒疾病已对全球公共卫生安全构成严重威胁.严重病例除了肺部疾病外伴有不同程度的肝损伤.以往研究表明,急性呼吸系统综合征冠状病毒和中东呼吸综合征冠状病毒感染者也可出现常见的肝损伤,且与疾病严重程度密切相关.主要从三大高致病性人类冠状病毒入手,分别阐述相关肝损伤的临床特点和机制,以供临床医生更清楚地认识该类病毒及作出更准确的决策.

摘要： 本文于2020年4月22日优先发布于中华眼科杂志官网 目的探讨眼部组织新型冠状病毒侵染和激活关键蛋白人血管紧张素转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)的情况,明确新型冠状病毒在眼部的侵染基础.方法 实验研究.选取30只小鼠,按性别、年龄、是否诱导糖尿病模型分为雄性组、雌性组、老年组、糖尿病组及糖尿病对照组,每组6只.使用荧光定量PCR分析小鼠结膜、角膜、泪腺、虹膜、晶状体、视网膜ACE2基因和TMPRSS2基因表达情况,并与肺脏、心脏、肾脏、肝脏中两个基因的表达量进行比较.使用免疫组化染色分析了小鼠各组织中ACE2和TMPRSS2蛋白的分布和表达情况.另取山东省眼科研究所红十字眼库接收的符合捐献条件的志愿者角膜及结膜组织切片,与小鼠眼部ACE2蛋白和TMPRSS2蛋白表达进行验证比较.同时通过分析已发表的人眼部组织转录组数据库,比较人角膜和结膜中ACE2和TMPRSS2基因的表达情况.对不同性别、年龄、及糖尿病条件下小鼠眼表组织的ACE2基因表达变化进行分析,采用独立样本t检验对数据进行统计学分析.对数据库中人角膜和结膜组织两种基因表达分析,采用Mann-Whitney U检验进行统计学分析.结果 在小鼠6种眼部组织中,结膜ACE2基因和TMPRSS2基因表达量最高,但均低于肾脏和肺脏;ACE2和TMPRSS2蛋白阳性染色集中于结膜上皮、角膜上皮和泪腺腺泡.ACE2基因的表达具有性别差异,在雌性小鼠结膜和角膜的表达显著低于雄性小鼠,分别为雄性相应组织的43％(t=3.269,P=0.031)和63％ (t=4.080,P=0.015);糖尿病小鼠结膜和泪腺中的ACE2基因表达略高于非糖尿病小鼠,分别为1.21倍和1.10倍(P＞0.05);不同年龄小鼠ACE2基因表达差异无统计学意义.与小鼠相似,人结膜ACE2和TMPRSS2基因表达量显著高于角膜(P=0.007),分别约为角膜上皮基因表达量的5.74倍和12.84倍.结论 结膜中ACE2和TMPRSS2的表达在6种检测的眼部组织中最高,提示结膜是新型冠状病毒眼部感染的主要靶组织.

摘要： 目的 采用改进的实验方法研究血管紧张素转换酶(ACE)基因rs1799752多态性与2型糖尿病(T2DM)肾病(DKD)的相关性,并探讨该多态性与环境因素(吸烟、肥胖)的交互作用对DKD的影响.方法 病例对照研究.选择2016年6月至2018年3月中日友好医院收治的T2DM合并DKD患者[DKD(+)组]和T2DM不伴DKD患者[DKD(-)组]各300例为研究对象.采用改进的PCR-毛细管电泳法进行基因分型.统计学分析两组受试者的临床生化指标和ACE基因I/D多态性不同基因型及等位基因频率,进一步按吸烟、肥胖状况分组进行多因素回归分析.结果 DKD(+)组患者DD基因型及D等位基因频率均高于DKD(-)组[DD基因型:15.0％(45例)比7.3％(22例),χ2=10.8,P=0.004;D等位基因频率:36.5％(219例)比28.0％(168例),χ2=9.92,P=0.02].多因素Logistic回归分析显示,在隐性和加性遗传模型中,D等位基因与DKD发病风险显著相关(校正后,隐性模型:OR=1.45,95％CI:1.06～2.00,P=0.022;加性模型:OR=1.41,95％CI:1.04～1.90,P=0.025).在吸烟组和肥胖组,D等位基因在显性和隐性模型中与DKD的发病显著相关(校正后均P0.05).结论 ACE基因I/D多态性与2型糖尿病患者DKD的发病相关,D等位基因是DKD发病的易感基因,DD基因型是2型糖尿病合并DKD的危险因素.ACE基因I/D多态性可能与吸烟、肥胖环境因素协同促进DKD的发病.%Objective To explore the interaction of angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism(rs1799752)with diabetic kidney disease (DKD) development as well as its interaction with smoking and obesity in Chinese type 2 diabetic mellitus (T2DM) using the improved experiment method. Methods From June 2016 to March 2018, 300 T2DM patients with DKD [DKD(+)] and 300 T2DM patients without DKD[DKD(-)] were selected from China-Japan Friendship Hospital. The improved Triple Primer Method that combined PCR with capillary electrophoresis was established in this study to detect the ACE genotype. The relevant clinical data as well as the frequencies of genotype and allele of ACE gene I/D polymorphism between two groups were statistically analyzed. Patients were further grouped based on smoking status and obesity for multivariate regression. Results Frequency of the DD genotype and D allele were significantly higher in DKD(+) group than in DKD(-) group [DD genotype:15.0％ (45 cases) vs 7.3％(22 cases),χ2=10.8, P=0.004;D allele:36.5％(219 cases) vs 28.0％(168 cases),χ2=9.92, P=0.02]. Multivariate logistic regression analysis found that D allele of rs1799752 was associated with a significantly higher risk of DKD in both recessive model(OR=1.45, 95％CI:1.06-2.00, P=0.022 after adjustments) and additive model(OR=1.41, 95％CI:1.04-1.90, P=0.025 after adjustments). In the smoker group and the obese group, D allele showed significant relationship with DKD incidence (P0.05). Conclusions I/D polymorphism of ACE gene is associated with the incidence of DKD in T2DM patients. DD genotype of the ACE gene is the risk factor for T2DM patients with DKD. D allele may increase DKD incidence in the presence of smoking and obesity.

摘要： Objective To evaluate the effect of angiotension-converting enzyme (ACE) gene poly-morphism on dexmedetomidine-induced inhibition of responses to extubation in the patients with hyperten-sion. Methods A total of 180 patients with primary hypertension, aged 50-63 yr, weighing 54-69 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective abdominal surgery under general anesthesia, in whom ACE genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism, were divided into 6 groups (n = 30 each) according to whether dexmedeto-midine was applied: DD genotype group (DD group), ID genotype group (ID group), Ⅱ genotype group (Ⅱ group), dexmedetomidine +DD genotype group (DEX+DD group), dexmedetomidine +ID genotype group (DEX+ID group) and dexmedetomidine+Ⅱ genotype group ( DEX+Ⅱ group). Dexmedetomidine 0. 5 μg·kg-1 ·h-1 was intravenously infused starting from 30 min before the end of surgery until the end of surgery in DEX+DD, DEX+ID and DEX+Ⅱ groups. Immediately before infusing dexmedetomidine (T1 ), at 30 min of dexmedetomidine infusion (T2 ), immediately after extubation (T3 ) and at 1. 5, 5 and 15 min after extubation (T4-6 ), systolic blood pressure, diastolic blood pressure, heart rate and ECG were recor-ded, and rate-pressure product was calculated. The development of myocardial ischemia and responses to extubation was recorded within 15 min after extubation. Results Compared with the baseline at T1 , each parameter of hemodynamics was significantly increased at T3-6 in DD, ID and Ⅱ groups (P 0. 05). Each parameter of hemodynamics was significantly lower at T3-6 , and the inci-dence of myocardial ischemia and responses to extubation was decreased in group Dex+DD than in group DD and in group Dex+ID than in group ID (P0. 05). Conclusion ACE gene polymorphism does not affect dexmedetomidine-induced inhibition of responses to extubation in the patients with hypertension.%目的 评价血管紧张素转换酶(ACE)基因多态性对右美托咪定抑制高血压患者气管拔管反应的影响.方法 选择全麻下行腹部手术的原发性高血压患者180例,年龄50～63岁,体重54～69 kg,ASA分级Ⅱ或Ⅲ级,术前采用RFLP-PCR法测定ACE基因型,并根据是否应用右美托咪定分为6组(n=30):DD基因型组(DD组)、ID基因型组(ID组)、Ⅱ基因型组(II组)、右美托咪定+DD基因型组(DEX+DD组)、右美托咪定+ID基因型组(DEX+ID组)和右美托咪定+Ⅱ基因型组(DEX+II组).DEX+DD组、DEX+ID组和DEX+Ⅱ组于手术结束前30 min静脉输注右美托咪定0.5μg·kg-1·h-1,直至术毕.于给予右美托咪定前即刻(T1)、给予右美托咪定30 min(T2)、气管拔管后即刻(T3)、气管拔管后1.5、5和15 min(T4-6)时,记录SP、DP、HR和ECG,并计算心率收缩压乘积;记录气管拔管后15 min内心肌缺血和气管拔管反应的发生情况.结果 与T1时比较,DD组、ID组和Ⅱ组T3-6时血流动力学各指标升高(P0.05);与DD组比较,Dex+DD组T3-6时血流动力学各指标降低,心肌缺血和气管拔管反应发生率降低(P0.05).结论 ACE基因多态性不会影响右美托咪定抑制高血压患者气管拔管反应.

摘要： 目的 探讨血管紧张素转换酶基因(ACE)I/D位点基因多态性与偏头痛易感性之间的关系.方法 通过检索PubMed和EMBASE数据库收集已发表的有关ACE I/D基因多态性与偏头痛易感性关系的病例对照研究,通过固定效应模型或随机效应模型合并效应量OR和95%CI以评价ACE I/D多态性与偏头痛易感性的关联性,同时进行种族及偏头痛类型亚组分析.结果 Meta分析中纯合子模型(DD vs.Ⅱ:OR=1.21,95%CI:1.02~1.44,P=0.03;I2=47%)和显性模型(DD+DI vs.Ⅱ:OR=1.16,95%CI:1.01~1.33,P=0.04;I2=50%)均提示ACE I/D多态性与所有偏头痛的易感性呈正相关.杂合子模型和显性模型提示ACE I/D多态性显著增加有先兆偏头痛的易感性.结论 ACE基因I/D位点多态性与偏头痛易感性相关,其D等位基因是偏头痛的危险因素,特别是显著增加有先兆偏头痛的易感性.%Objective To investigate the association between the angiotensin-converting enzyme (ACE) I/D locus polymor-phism and migraine susceptibility .Methods The case control studies on the relation between ACE I/D gene polymorphism and mi-graine susceptibility published in the databases of PubMed and EMBAE were retrieved .The relationship between ACE 1/D poly-morphism and migraine was evaluated through the effect size (OR) and 95% confidence interval(CI) by fixed-effects model or ran-dom-effect models .Meanwhile the subgroup analysis of ethnicity and migraine types was performed .Results In meta analysis ,the homozygote model(DD vs .Ⅱ:OR= 1 .21 ,95% CI:1 .02-1 .44 ,P=0 .03 ;I2 =47% ) and dominant model all indicated that the ACE I/D polymorphism was positively correlated with the susceptibility of all migraine .The heterozygote model (DI vs .Ⅱ:OR=1 .35 , 95% CI:1 .06-1 .72 ,P=0 .02 ;I2 =10% ) and dominant model (DD+DI vs .Ⅱ:OR=1 .37 ,95% CI:1 .09 -1 .73 ,P=0 .00 ;I2 =40% ) indicated that ACE I/D polymorphism significantly increased the susceptibility of migraine with aura .Conclusion The ACE I/D locus polymorphism is correlated with migraine susceptibility ,its D allele is a risk factor of migraine ,which especially increases the susceptibility of migraine with aura .

摘要： 目的 探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与多囊卵巢综合征(PCOS)的关系.方法 选择2007年5月至2011年3月,于南京大学医学院附属鼓楼医院妇产科就诊的217例PCOS患者为研究对象,纳入PCOS组.选择同期于本院参加健康体检的188例妇女,纳入对照组.采集2组受试者的血液标本.采用放射免疫法,检测2组受试者血清促黄体激素(L H)、卵泡刺激素(FS H)、雌二醇、睾酮水平.采用聚合酶链反应-限制性片段长度多态性法,对2组受试者ACE基因I/D多态性基因型进行检测.统计学比较2组受试者的年龄、人体质量指数(BMI)、ACE基因I/D多态性不同基因型及等位基因频率,并分别对A CE基因I/D多态性不同基因型的PCOS组和对照组受试者的年龄、BM I及血清性激素水平进行统计学比较.本研究经过南京大学医学院附属鼓楼医院医学伦理委员会批准,分组征得受试者知情同意,并与之签署临床研究知情同意书.2组受试者月经初潮年龄等基本临床资料比较,差异均无统计学意义(P>0.05).结果 ①PCOS组受试者的年龄、血清FSH水平均低于对照组,BMI及血清LH、雌二醇、睾酮水平均高于对照组,并且差异均有统计学意义(t=-12.630、6.528、-3.961、12.091、6.534、19.888,P0.05);ACE基因I/D多态性不同基因型受试者的血清LH、睾酮水平及LH与FSH比值(LH/FSH)比较,差异均有统计学意义(F=14.721、19.609、20.685,P0.05).结论 ACE基因I/D多态性与PCOS的易感性无关,但等位基因D可能与高血清睾酮、L H水平有关.由于本研究纳入样本量相对较小,A CE基因I/D多态性与PCOS的关系,仍需大样本、多中心、随机对照研究进一步试验、证实.%Objective To explore the relationship between I/D polymorphism of angiotensin-converting enzyme (ACE) gene and polycystic ovarian syndrome (PCOS) .Methods From May 2007 to March 2011 ,a total of 217 cases with PCOS who were admitted to Nanjing Drum Tower Hospital , Affiliated Hospital of Nanjing University Medical School were included into this study as PCOS group .Meanwhile ,another 188 cases who received physical examinations were included as control group .The blood samples of two groups were collected . The serum luteinizing hormone (LH ) , follicle-stimulating hormone ( FSH ) , estradiol and testosterone levels were measured by radioimmunoassay method . Genotypings of the ACE gene polymorphism were conducted by the polymerase chain reaction-restriction fragment length polymorphism method .The age ,body mass index (BMI) ,frequencies of genotype and allele of ACE gene I/D polymorphism between two groups , and age ,BMI ,levels of serum gonadal hormones among different I/D genotypings in PCOS group and control group were statistically compared .The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Nanjing Drum Tower Hospital , Affiliated Hospital of Nanjing University Medical School .Informed consent was obtained from each participants .There were no significant differences between two groups in the basic clinical data ,such as menarche age and so on (P>0 .05) .Results ①The age and level of serum FSH in PCOS group were lower than those in control group ,while the BMI ,levels of serum LH ,estradiol and testosterone in PCOS group were all higher than those in control group ,and all the differences were statistically significant (t=-12 .630 ,6 .528 ,-3 .961 ,12 .091 ,6 .534 ,19 .888;P 0 .05);while as to the levels of serum LH ,testosterone and LH/FSH ratio ,all the differences were statistically significant (F= 14 .721 ,19.609 ,20 .685 ;P0 .05) .Conclusions ACE gene I/D polymorphism is not associated with the susceptibility of PCOS ,but the allele D may contribute to the high levels of serum testosterone and LH .As the sample size in this study is relatively small ,the association of A CE gene I/D polymorphism and PCOS still requires large sample ,multicenter ,and randomized controlled studies to confirm .

摘要： 本发明提供调控害虫的生理条件的试剂，其中所述试剂具有调控昆虫肽基-二肽酶A活性的能力；用于检测测试物质的杀虫活性的方法，其包括在肽基-二肽酶A与测试物质接触的反应系统中检测肽基-二肽酶A活性的步骤，等等。

摘要： 本发明提供了式(I)的化合物、其制备方法、含有其的药物组合物和其作为二肽基肽酶I(DPPI)抑制剂的用途，其中n、y、X

摘要： 本发明涉及一种用于通过对这些细胞表达的氨基肽酶N(APN)和二肽基肽酶Ⅳ(DP Ⅳ)抑制剂的单独或联合作用抑制人皮脂细胞的增生所必须的DNA合成的方法。给予的APN和/或DP Ⅳ的抑制剂后对人皮脂细胞DNA的合成(增生)是剂量依赖性的。我们的发明显示，为了治疗和预防因皮脂细胞的过度增生和分化状态改变导致的皮肤疾病，使用上面提及的酶抑制剂和它的相应药物制剂及给药形式是适合的。

摘要： 一株胞外分泌表达桦褐孔菌二肽酶的工程菌，通过利用克隆的桦褐孔菌去跨膜区的二肽酶基因IDP与表达载体可操作地连接，得到能够表达该蛋白的重组表达载体，并将上述重组表达载体导入恰当的宿主细胞中而获得。本发明还提供一种制备上述IDP的方法，其是通过培养IDP‑X33，经甲醇诱导表达获得桦褐孔菌去跨膜区的二肽酶IDP。所述培养条件为28°C，初始pH为7，200rpm培养96小时。所述诱导条件为每24小时补充一次诱导物甲醇，至甲醇终浓度为1.0％。本发明的提供的重组毕赤酵母表达二肽酶方法，胞外分泌酶活达到24U/mL，细胞密度(OD600)为24.5，酶的分泌效率为1U/mL。

摘要： 下式所示的化合物，式中R

摘要： 本发明提供调控害虫的生理条件的试剂，其中所述试剂具有调控昆虫肽基－二肽酶A活性的能力；用于检测测试物质的杀虫活性的方法，其包括在肽基－二肽酶A与测试物质接触的反应系统中检测肽基－二肽酶A活性的步骤，等等。

摘要： 本发明涉及式(I)化合物及其作为选择性二肽基肽酶I抑制剂的用途，以及包括所述化合物的药物组合物和涉及所述化合物的治疗方法。

摘要： 本发明提供了式(I)的化合物、其制备方法、含有其的药物组合物和其作为二肽基肽酶I(DPPI)抑制剂的用途，其中n、y、X

摘要： 本发明涉及一种用于通过对这些细胞表达的氨基肽酶N(APN)和二肽基肽酶IV(DP IV)抑制剂的单独或联合作用抑制人皮脂细胞的增生所必须的DNA合成的方法。给予的APN和/或DP IV的抑制剂后对人皮脂细胞DNA的合成(增生)是剂量依赖性的。我们的发明显示，为了治疗和预防因皮脂细胞的过度增生和分化状态改变导致的皮肤疾病，使用上面提及的酶抑制剂和它的相应药物制剂及给药形式是适合的。

摘要： 提供了用于预防或治疗癌症的方法。该方法针对以突变p53的表达为特征的癌症。突变p53可以是功能丧失p53突变体、显性负p53突变体或功能获得p53突变体。该方法包括向癌细胞递送可以抑制氨酰基脯氨酸二肽酶(PEPD)表达或破坏突变p53与PEPD缔合的药剂。