自发性高血压大鼠原癌基因表达和限制性内切酶片段长度多态性分析

观察自发性高血压大鼠（ＳＨＲ）血管平滑肌细胞（ＶＳＭＣｓ）的生长曲线、ｃ－ｆｏｓ原癌基因表达和ｃ－ｆｏｓ基因酶切图谱的情况,与对照组京都维斯特大鼠（ＷＫＹ）进行对比．结果显示,在小牛血清作用下ＳＨＲ的ＶＳＭＣｓ生长速率和ｃ－ｆｏｓ原癌基因表达明显大于ＷＫＹ;ｃ－ｆｏｓ原癌基因限制性内切酶片段长度多态性（ＲＦＬＰ）分析表明,经ＢａｍＨⅠ或ＥｃｏＲⅠ酶切后的ＳＨＲ和ＷＫＹ的酶切图谱一致,同时也未发现ＳＨＲ的ｆｏｓ基因扩增现象．提示,ＶＳＭＣｓ的异常增殖和ｃ－ｆｏｓ原癌基因的表达异常与高血压的形成有关,而ｃ－ｆｏｓ原癌基因的过度表达可能是由于某些与基因转录调控有关的因素异常所致．     

G蛋白－肌醇磷脂途径及其与高血压的关系

作为第二信使的三磷酸肌醇（ｉｎｏｓｉｔｏｌ－１,４,５－ｔｒｉｓｐｈｏｓｐｈａｔｅ,ＩｎｓＰ３）主要经２种途径形成：Ｇ蛋白偶联受体和酪氨酸激酶偶联受体。两类受体激活各自相应的磷脂酶Ｃ（ｐｈｏｓｐｈｏｌｉｐａｓｅＣ,ＰＬＣ）而水解磷脂酰肌醇－４,５－二磷酸（ｐｈｏｓｐｈａｔｉｄｙｌｉｎｏｓｉｔｏｌ－４,５－ｂｉｓｐｈｏｓｐｈａｔｅ,ＰｔｄＩｎｓ４．５Ｐ２）形成ＩｎｓＰ３和二酯酰甘油（ｄｉａｃｙｌｇｌｙｃｅｒｏｌ,ＤＧ）。ＩｎｓＰ３形成后动员储存钙和促进外源性钙内流。近年来的研究证实,Ｇｑ是调节ＰＬＣ－β１活性的特导性Ｇ蛋白,Ｇｑ系列α亚单位包括Ｇαｑ、Ｇα１１、Ｇα１４、Ｇα１５和Ｇα１６。高血压的重要病理基础是动脉血管壁的痉挛和增殖,许多血管活性物质可以促使血管平滑肌细胞的收缩和增生,同时伴有细胞内ＩｎｓＰ３产生增加．但高血压并不能造成Ｇｑ量的持续改变。     

Synthesis and evaluation of novel angiotensin II receptor 1 antagonists as anti-hypertension drugs

Three new angiotensin II receptor 1 antagonists, 1, 2 and 3 were designed, synthesized and evaluated. The AT₁ receptor-binding assays in vitro showed that all the synthesized compounds had nanomolar affinity for the AT₁ receptor. From which compound 3 was found to be the most potent ligands with an IC₅₀ value of 2.67 ± 0.23 nM. Biological evaluation in vivo revealed that all the compounds could cause significant decrease on MBP in a dose dependent manner in spontaneously hypertensive rats, and compound 3 especially showed an efficient and long-lasting effect in reducing blood pressure, whose maximal response lowered 41 mmHg of MBP at 10 mg/kg and 62 mmHg at 15 mg/kg after oral administration, the significant anti-hypertensive effect lasted beyond 12 h, which is better than the reference compound losartan. The pharmacokinetic experiments showed that compound 3 could be absorbed efficiently and metabolized smoothly both in blood and in tissues in Wistar rats. The acute toxicity assay suggested that it has low toxicity with the LD₅₀ value of 2974.35 mg/kg. These results demonstrate that compound 3 is a potent angiotensin AT₁ receptor antagonist which could be considered as a novel anti-hypertension candidate and deserved for further investigation.     

老年高血压前期患者糖耐量降低对内皮功能及颈动脉粥样硬化的影响

目的:探讨老年人高血压前期糖耐量降低(IGT)对血管内皮功能和颈动脉粥样硬化的影响。方法:选择2013年1月至2014年1月在我院门诊、住院和体检中心纳入的60岁以上志愿者240例,依据血压、血糖水平将志愿者分为四组,单纯高血压前期(PH)组,单纯IGT(IGT)组,高血压前期并发IGT(PHIGT)组,正常对照(NC)组,每组均为60例。检测颈动脉内中膜厚度(IMT)和内皮依赖性血管舒张功能(FMD)并进行相关性分析。结果:与NC组相比,IMT在PH组、IGT组和PHIGT组显著升高[(0.74±0.09)mm、(0.76±0.12)mm、(0.96±0.14)mm vs(0.57±0.08)mm,均P0.05],且PHIGT组相比于PH组和IGT组进一步升高(P0.05);与NC组相比,FMD在PH组、IGT组和PHIGT组显著降低[(8.77±2.56)%、(8.59±2.37)%、(5.78±2.11)%vs(12.48±2.78)%,均P0.05],且PHIGT组相比于PH组和IGT组进一步下降(P0.05)。直线相关分析显示,IMT与FMD呈显著负相关,相关性检验有统计学意义(r=-0.843,P0.01)。结论:高血压前期患者血管内皮功能受损,在高血压前期基础上的IGT将会加剧血管内皮功能障碍和动脉粥样硬化。     

Dermatoglyphic traits in patients with cardiovascular disorders

Dermatoglyphic studies were carried out on 800 Japanese subjects. Digital dermal pattern types were classified into true whorls, double loops, ulnar loops, radial loops and arches. Both total and absolute ridge count were recorded. Subjects with hypertension, angina pectoris and myocardial infarction were compared with the remaining group of others who had not yet developed any of these disorders. Individuals with myocardial infarction had a significantly higher frequency of true whorls and a correspondingly lower frequency of ulnar loops than the control group. Total and absolute ridge counts were also significantly higher in myocardial infarction. Individuals with hypertension and angina pectoris were not significantly different in most dermatoglyphic traits from the controls. These observations suggest that antenatal factors may contribute to the etiology of myocardial infarction in man.     

血脂、血小板参数、HOMA-IR与阻塞性睡眠呼吸暂停低通气综合征合并高血压患者PSG参数的相关性及其预测价值研究

摘要 目的：探讨血脂、血小板参数、稳态模型胰岛素抵抗指数（HOMA-IR）与阻塞性睡眠呼吸暂停低通气综合征（OSAHS）合并高血压患者多导睡眠图（PSG）参数的相关性及其预测价值。方法：选择2020年1月至2022年11月徐州医科大学附属沭阳医院收治的163例OSAHS患者，根据是否合并高血压将其分为单纯OSAHS组（78例）及高血压组（85例），检测两组血脂、血小板参数、HOMA-IR、PSG参数；Pearson相关性分析血脂、血小板参数、HOMA-IR与PSG参数的相关性；多因素Logistic回归分析OSAHS合并高血压的危险因素；受试者工作特征（ROC）曲线分析血脂、血小板参数、HOMA-IR预测OSAHS合并高血压的价值。结果：高血压组甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、平均血小板体积（MPV）、HOMA-IR、微觉醒指数（MAI）、呼吸暂停低通气指数（AHI）、氧减指数（ODI）高于单纯OSAHS组（P＜0.05），高密度脂蛋白胆固醇（HDL-C）水平低于单纯OSAHS组（P＜0.05）。高血压组TG、TC、LDL-C、MPV、HOMA-IR与MAI、AHI、ODI呈正相关（P＜0.05），HDL-C与MAI、AHI、ODI呈负相关（P＜0.05）。高体质量指数、高HOMA-IR及TG、MPV水平升高是OSAHS患者合并高血压的危险因素（P＜0.05）。联合TG、MVP、HOMA-IR预测OSAHS患者合并高血压的曲线下面积高于以上三指标单独预测。结论：OSAHS合并高血压患者TG、MPV水平及HOMA-IR显著增高，且与MAI、AHI、ODI呈正相关，TG、MPV、HOMA-IR联合检测对OSAHS患者合并高血压的预测价值较高。     

白杨素对高血压大鼠的降压作用及机制研究

摘要 目的：探讨白杨素对高血压大鼠的降压作用及作用机制。方法：8只WKY大鼠为对照组，40只SHR大鼠随机分为模型组、卡托普利组和白杨素高、中、低剂量组，分别给予相应剂量药物治疗，每日1次，干预4周。实验期间观察各组大鼠收缩压（SBP）和舒张压（DBP）改善情况，酶联免疫吸附法（ELISA ）检测大鼠动脉血清中一氧化氮合酶（eNOS）、一氧化氮（NO）、内皮素（ET-1）和血管紧张素Ⅱ（AngⅡ）水平，马松染色（Masson）和苏木精-伊红染色法 ( HE) 观察大鼠心肌组织病理变化。结果：治疗后，与模型组相比，对照组、卡托普利组和白杨素高、中、低剂量组SBP和DBP均明显下降，血清eNOS和NO显著上升，ET-1和AngⅡ明显下降，差异具有统计学意义（P＜0.05），其中白杨素高剂量组改善情况优于白杨素低、中剂量组（P＜0.05）；心肌细胞相关病理损伤减轻，白杨素高剂量组改善情况优于白杨素中、低剂量组。结论：白杨素可能通过调节血管舒缩因子和肾素-血管紧张素-醛固酮系统降低血压，并改善心肌组织病理损伤。     

Variant rs2237892 of KCNQ1 Is Potentially Associated with Hypertension and Macrovascular Complications in Type 2 Diabetes Mellitus in A Chinese Han Population

KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus(T2DM) in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2 DM complications remain unclear. To further analyze the association between different alleles at the single nucleotide polymorphism(SNP) rs2237892 within KCNQ1 and TD2 M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM(odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20–1.75). Genotypes CT(OR, 1.97; 95% CI,1.24–3.15) and CC(OR, 2.49; 95% CI, 1.57–3.95) were associated with an increased risk of T2 DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure(P = 0.015), prevalence of hypertension(P = 0.037), and risk of macrovascular disease(OR, 2.10; CI, 1.00–4.45) were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or     

H型高血压合并阻塞性睡眠呼吸暂停低通气综合征的观察

目的:探讨H型高血压与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的相互关系。方法:选择2013年10月至2014年8月在上海市浦南医院心内科就诊的78例高血压住院患者,血浆同型半胱氨酸(Hcy)水平≥10μmol/L为H型高血压、血浆Hcy水平10μmol/L为单纯性高血压。两者分别用便携式睡眠监测仪(PMD)检测,比较两组结果的差异。结果:H型高血压组的呼吸暂停低通气指数(AHI)高于单纯性高血压组(P0.05),H型高血压组的OSAHS发病率与单纯组无差异(P0.05),在有OSAHS的高血压病人中,H型高血压组有较高的中重度OSAHS的发病率(P0.01)。结论:在高血压患者中,没有发现血浆Hcy水平与OSAHS相关。但是一旦存在OSAHS,则合并H型高血压患者中出现中重度OSAHS的概率较高。