Wnt信号通路与高血压疾病的研究进展

Wnt信号分子是一类在无脊椎与脊椎动物的多种组织中广泛表达且进化上高度保守的信号刺激分子,他们在生长、发育、代谢和干细胞调节等多种生物学过程中发挥重要作用。在健康成人的器官中Wnt信号是沉默的,但是在病理情况下Wnt信号激活。近年发现Wnt信号通路在心血管疾病的发生发展过程中扮演重要角色。本文将详细介绍Wnt信号通路,及其与高血压疾病的研究进展,试图将对Wnt信号通路的调控作为治疗高血压疾病的新的方向。     

16S rRNA技术检测盐诱导高血压大鼠肠道菌群的变化

目的 检测高血压大鼠肠道菌群的变化,探讨正常菌群在盐诱导高血压发生发展中的作用。方法 以8%高盐饮食喂养SD雄性大鼠制备高血压模型。Real-time PCR检测菌群结构的改变,同时检测血浆炎性因子IL-1β、IL-6和TNF-α水平变化。结果 同对照组大鼠血压（96.00 mmHg±5.74 mmHg）相比盐敏感组（122.79 mmHg±6.37 mmHg）显著升高,而盐抵抗组无明显变化;实验组大鼠体重（172.00 g±15.58 g,164.25 g±16.11g）较对照组（377.63 g±32.47 g）明显降低;同对照组相比实验组菌群结构发生比例倒置,即双歧杆菌（6.19±0.47,7.52±0.47 vs 8.59±0.42）、乳杆菌（6.77±0.23,7.09±0.28 vs 7.60±0.26）、拟杆菌（8.98±0.45,8.46±0.47 vs 9.99±0.73）数量降低;肠杆菌（7.93±0.20,7.78±0.29 vs 7.28±0.27）数量升高。同盐抵抗组大鼠相比,盐敏感组双歧杆菌、乳杆菌降低更加显著,但拟杆菌数量高于盐抵抗组。两实验组大鼠血浆细胞因子IL-1β、IL-6和TNF-α水平较对照组均显著升高（P<0.05）。结论 盐诱导高血压大鼠肠道菌群结构发生改变,盐敏感组双歧杆菌、乳杆菌和拟杆菌含量显著降低,提示其可能参与盐诱导高血压病程。     

薛氏4号方联合苯磺酸氨氯地平片治疗湿热侵络型高血压的疗效及对血脂和血液流变学的影响

摘要 目的：观察湿热侵络型高血压患者经苯磺酸氨氯地平片联合薛氏4号方治疗后的疗效及其对血脂和血液流变学的影响。方法：采用随机数字表法将2020年1月~2022年12月期间石家庄市中医院收治的120例湿热侵络型高血压患者分为对照组（n=60,苯磺酸氨氯地平片治疗）及联合组（n=60,对照组基础上接受薛氏4号方治疗）。观察两组治疗4周后的临床疗效,对比两组治疗前、治疗4周后的血压、中医证候积分、血脂和血液流变学情况。结果：联合组的临床总有效率高于对照组（P<0.05）。联合组治疗4周后收缩压（SBP）、舒张压（DBP）低于对照组（P<0.05）。联合组治疗4周后眩晕、头痛、口渴少饮、肢体困重、失眠、心悸、胸闷、肢体麻木中医证候积分低于对照组（P<0.05）。联合组治疗4周后甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）低于对照组,高密度脂蛋白胆固醇（HDL-C）高于对照组（P<0.05）。联合组治疗4周后红细胞聚集指数、血小板最大聚集率、全血高切黏度、全血低切黏度低于对照组（P<0.05）。结论：薛氏4号方联合苯磺酸氨氯地平片治疗湿热侵络型高血压,可提高临床疗效,降低血压,降低中医证候积分,改善血脂和血液流变学。     

Altered regulation of renal sodium transporters and natriuretic peptide system in DOCA–salt hypertensive rats

Although deoxycorticosterone acetate (DOCA)–salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA–salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of α-1 subunit of Na,K–ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA–salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis.     

全身麻醉联合硬膜外麻醉在腹腔镜胆囊切除术高血压患者中的应用效果观察

目的:探讨全身麻醉联合硬膜外麻醉对腹腔镜胆囊切除术(LC)高血压患者麻醉效果、血流动力学和T细胞亚群的影响。方法:选取2017年3月～2019年3月期间我院收治的113例行LC的高血压患者,采用随机数字表法分为对照组(n=56)和研究组(n=57),对照组患者予以全身麻醉,研究组在对照组的基础上联合硬膜外麻醉,比较两组患者麻醉效果、血流动力学[心率(HR)、平均动脉压(MAP)]、T细胞亚群、术后恢复情况及并发症。结果:研究组的麻醉效果优良率为91.23%(52/57),高于对照组的76.79%(43/56)(P0.05)。研究组麻醉诱导前(T1)、插管后2 min(T2)、气腹后10 min(T3)、术中探查(T4)、术毕气管导管拔出2 min后(T5)时间点HR、MAP无明显变化,对照组T1～T5时间点HR、MAP呈现先下降后升高趋势(P0.05);研究组T1、T2时间点HR高于对照组,T4和T5时间点HR则低于对照组(P0.05);研究组各时间点MAP均低于对照组(P0.05)。两组术毕1d(T6)、术毕3d(T7)时间CD4~+、CD4~+/CD8~+均较T1较低,CD8~+较T1升高,但研究组CD4~+、CD4~+/CD8~+高于对照组,CD8~+则低于对照组(P0.05)。研究组术后睁眼时间、定向力恢复时间、拔管时间均短于对照组(P0.05)。两组并发症发生率比较无差异(P0.05)。结论:高血压患者行LC时给予全身麻醉联合硬膜外麻醉,麻醉效果显著,可有效稳定机体血流动力学,减轻免疫抑制,促进患者术后意识恢复,且不增加并发症发生率。     

高血压合并动脉粥样硬化与血管紧张素原相关性的研究

目的：探讨高血压合并动脉粥样硬化与血管紧张素原的相关性。方法：30只雄性16周龄SHR大鼠随机均分为SHR组和SHR合并AS组,另设15只同龄雄性WKY大鼠作为正常血压对照组即WKY组。SHR合并AS组饲以高脂饲料并辅以大剂量VitD3灌胃建立高血压动脉粥样硬化大鼠模型,SHR组和15只同龄雄性WKY大鼠均饲以标准饲料。各组大鼠分别于0、6、12周时光镜、电镜下评估血管病变,全自动生化分析仪检测血脂水平,并采用ELISA法检测血清AGT、AngII浓度。结果：SHR血清AGT、AnglI浓度显著高于WKY大鼠（P〈0．05）。存在AS病变的SHR合并AS组,血清AGT、AngII浓度明显高于无AS病变的SHR组,且随着AS病变严重性的增加,血清AGT、AngII浓度亦增加（P〈0．05）。结论：抑制AGT的表达可能为高血压患者中AS的防治提供一种新的方法。     

脉搏波传导速度检测在评价高血压病患者大动脉弹性中的应用 与影响因素分析

目的:探讨脉搏波传导速度(PWV)检测在评估高血压病患者大动脉弹性中的应用价值与影响因素分析 方法:采用分层整体抽样法随机抽取高血压病患者2178例,同时抽取非高血压2182人作为对照组.应用Complior SP VP-1000动脉硬化检测仪测定颈一股动脉脉搏波传导速度(C-FPWV)评估大动脉弹性.采用多元逐步线性回归分析性别、年龄、体质指数(BMI)、收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、甘油三脂(TG)、空腹血糖(FPG)和尿酸(UA)等指标与高血压痛患者大动脉弹性下降的影响因素.结果:C-FPWV平均值高血压组(1594± 264cm/s)显著高于对照组(1216± 231cm/s),两组差异有显著性意义(X2=31.659,P=0.00).＞40岁各年龄段PWV值上升程度,高血压组明显高于对照组(X2＝ 18.954～36.924,P=0.00),两组PWV值上升程度与年龄呈正相关.多元逐步线性回归分析表明:BMI≥28kg/m2、SBP≥ 140mmHg、DBP≥90mmHg、TC＞5.28± 0.62 mmol/L、TG＞ 1.68± 0.64mmol/L等指标高血压组明显高于对照组(t=14.314～17.428,P＜0.05).在性别、UA和FPG等指标两组无明显差异(X2=6.368～13.618,P＞0.05).结论:高血压痛患者PWV值上升程度显著高于非高血压者,BMI、SBP、TG、TC是高血压病患者大动脉弹性下降的主要影响因素.PWV值可作为评价大动脉弹性的可靠指标.     

Homology modeling, active site prediction, and targeting the anti hypertension activity through molecular docking on endothelin - B receptor domain

In cardiovascular system, activation of Endothelin receptors causes vasoconstriction which leads to Pulmonary Arterial Hypertension (PAH). Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension. Bosentan is intended to affect vasoconstriction, hypertrophic and fibrotic effects by blocking the actions of receptors ET(A) and ET(B). In this study we identified the action of Bosentan on endothelin B receptor using docking studies with homology modeled endothelin B receptor. Through the modeled protein, the flexible Docking study was performed with Bosentan and its derivatives with theoretically predicted active sites. The results indicated that amino acid ARG82, ARG84 and HIS197 present in endothelin B receptor are core important for binding activities and these residues are having strong hydrogen bond interactions with Bosentan. We have investigated the Bosentan and its derivatives interactions and scoring parameters using gold docking package. Among the docked compounds, one of the Bosentan derivatives BD(6) shows better interaction than Bosentan with endothelin B receptor. Our results may be helpful for further investigations in both in vivo and in vitro conditions.