Advance on Chinese Medicine for Hypertensive Renal Damage:Focus on the Complex Molecular Mechanisms

Hypertensive renal damage(HRD)is a major cause of end-stage renal disease.Among the causes of end-stage renal disease,HRD accounts for nearly 34%of the total number of cases.Antihypertensive treatment is primarily drug-based,but therapeutic efficacy is less effective and can have serious side effects.Chinese medicine(CM)has significant advantages in the treatment of HRD.CM is rich in various active ingredients and has the property of targeting multiple targets and channels.Therefore,the regulatory network of CM on disease is complex.A large number of CM have been employed to treat HRD,either as single applications or as part of compound formulations.The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system,antioxidation,anti-inflammation,rescue of endothelial function,regulation of vasoactive substance secretion and obesity-related factors,etc.This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

Clinical characteristics, target organ damage and associate risk factors ofresistant hypertension determined by ambulatory blood pressure monitoringin patients aged ≥80 years

Objectives To investigate clinical characteristics, target organ damage, and the associated risk factors of the patients aged ≥ 80 yearswith true resistant hypertension （RH）. Methods Patients aged ≥ 80 years with hypertension （n = 1163） were included in this study. Theincluded participants attended a structured clinical examination and an evaluation of RH was carried out. The prevalence, clinical characteristicsand target organ damage of patients with RH were assessed. The associated clinical risk factors were analyzed by using logistic regression.Results The prevalence of RH diagnosis by 24-h ambulatory blood pressure monitoring assessment was 21.15%. End-diastolic left ven-tricular internal dimension, left ventricular mass index as well as prevalence of left ventricular hypertrophy were significantly greater in pa-tients with RH than in control group. The common carotid artery intimal media thickness, carotid walls thickness, common carotid arterydiameter and relative wall thickness were significant greater in RH group than in control. A relatively higher level of creatinine, estimatedglomerular filtration rate, microalbuminuria and retinal changes was found in RIt group than in control. A multivariate analysis showed thatpatients with a history of diabetes, higher body mass index （BMI） and lipid profiles were independent risk factors of RH. Conclusions Theprevalence of RH in patients aged ≥ 80 years was within the range of reported rates of the general population. Subjects with RH diagnosisshowed a higher occurrence of target organ damage than patients with well controlled blood pressure. Patients with diabetes, higher BMI andserum lipid profiles were independent risk factors for RH in patients aged ≥ 80 years.

Characteristics of Optic Nerve Damage Induced by Chronic Intraocular Hypertension in Rat

Purpose:To set up the Sharma’s chronic intraocular hypertension model and investigate the intraocular pressure (IOP) as well as the optic nerve damage of this model in rat. Methods:The operations of the chronic intraocular hypertension model were performed as described by Sharma in 60 male Lewis albino rats. IOP was measured using the Tono-Pen XL immediately after surgery and then at 5 day, 2 week or 4 week intervals. Cresyl violet staining of whole-mounted retinas was used to label retinal ganglion cells (RGCs), then RGCs were counted. Paraphenylenediamine (PPD) staining was performed in the semi-thin cross sections of optic nerve of rat, in order to know whether the axons of optic nerve were degenerated or not. Results:There were 47 rats with higher IOP after the episcleral veins cauterized in 60 rats. The ratio of elevated IOP was 78.3%. The IOPs were stable in 4 weeks. After cresyl violet staining, the RGCs loss was 11.0% and 11.3% was found in the central and peripheral retina respectively after 2 weeks of increased IOP. After 4 weeks of increased IOP, the loss of RGCs was 17% for the central retina and 24.6% for the peripheral retina. In the retinas without higher IOP, there was no loss of RGCs. PPD staining showed that optic nerve of rat with about 5.3% damage of axons located at the superior temporal region. Region of affected optic nerve 1 mm posterior to the globe by light microscope showed evidence of damaged axons with axonal swelling and myelin debris. Conclusion:Sharma’s chronic intraocular hypertension model is a reproducible and effective glaucoma model, which mimics human glaucoma with chronically elevation IOP and induced RGCs loss and damage of optic nerve. Eye Science 2004;20:25-29.

Effect of anesthetics on gastric damage using two models of portal hypertension

AIM:To investigate the effect of sodium pentobarbitone(SP) or ketamine/xylazine(KX) anesthetics on acute gastric injury.METHODS:Portal hypertension was induced by bile duct ligation(BDL) or portal vein stenosis(PVS).Ethanol(EtOH)-induced gastric damage was assessed using ex vivo gastric chamber experiments.Gastric blood flow(GBF) was also measured by laser doppler flowmetry.RESULTS:EtOH-induced gastric damage was reduced in BDL rats under KX anesthesia in comparison to those under SP anesthesia.GBF dysfunction in fasted BDL rats was partially restored under KX anesthesia.In contrast,in fasted PVS rats,EtOH-induced gastric damage was increased under KX anesthesia while GBF was reduced.CONCLUSION:The use of KX anesthesia in experimental procedures involving cirrhotic rats(but not those with pure portal hypertension) is preferable to SP anesthesia.

Resistive Cerebral Blood Flow as a Potential Marker of Subclinical Brain Damage in Essential Hypertension

Introduction: Subclinical brain damage in essential hypertension is more prevalent than cardiovascular or renal impairment;nevertheless, screening for nervous system involvement is difficult due to the low accessibility and high costs of these techniques. Objective: To assess the frequency of silent target organ damage in a cohort of asymptomatic hypertensive patients and to evaluate the potential usefulness of carotid ultrasonographic (US) variables as predictors of subclinical brain damage. Patients and Methods: Thirty four neurologically asymptomatic subjects (mean age 59 years) with essential hypertension were included. Target organ damage was evaluated: degree of hypertensive retinopathy, heart, kidney and brain. Structural and hemodynamical carotid Doppler US parameters were also investigated. Results: The brain was the most frequently affected target organ (70.6%), followed by the heart (67.9%) and kidney (58.6%). Carotid US parameters showed no association of intima media thickness with brain MRI results;nevertheless, decreased diastolic flow velocity and increased resistive index pointed to a resistive carotid flow pattern in patients with classical brain MRI lesions and predicted subclinical lesions with a sensitivity of 70% and 74% and a specificity of 72% and 80% respectively. Conclusions: This study supports previous findings that place the brain as the most frequently affected target organ in essential hypertensive patients and sheds more light on the potential usefulness of carotid structure and hemodynamics as imaging biomarkers of subclinical brain lesions.

Metabolic syndrome in hypertensive patients:An unholy alliance

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.

End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899

AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage. METHODS: Long-term pharmacological characterization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition and the other is insensitive [deoxycorticosterone acetate(DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension. RESULTS: Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calciumchannel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension. CONCLUSION: Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.

Effects of sufentanil/fentanyl combined with propofol on the anesthesia of minimally invasive drainage for hypertensive cerebral hemorrhage

Objective: To compare the effects of sufentanil/fentanyl combined with propofol on the anesthesia of minimally invasive drainage for hypertensive cerebral hemorrhage. Methods:Patients with hypertensive cerebral hemorrhage who received minimally invasive drainage in Huanggang Cerebrovascular Hospital between June 2014 and February 2017 were selected and randomly divided into two groups, observation group received sufentanil combined with propofol anesthesia, and control group received fentanyl combined with propofol anesthesia. The serum contents of nerve injury, stress response, oxidation reaction and inflammatory response markers were measured during surgery and 12 h after surgery. Results: During surgery and 12 h after surgery, serum TF, NSE, GFAP, GLU, NE, E, ACTH, Cor, Ins, MDA, AOPP, 8-OHdG, NO, ICAM-1, TNF-α, IL-6, IL-17 and IL-23 levels of observation group were significantly lower than those of control group. Conclusion: Sufentanil combined with propofol for minimally invasive drainage of hypertensive cerebral hemorrhage is more effective than fentanyl combined with propofol to reduce the brain damage and inhibit the inflammatory response, stress response and oxidation reaction.

基于ACE/AngⅡ/AT1R通路探讨补肾降压方对盐敏感性高血压大鼠肾纤维化的作用机制

目的:探讨补肾降压方对盐敏感性高血压DS大鼠肾纤维化及肾素血管紧张素转换酶-血管紧张素Ⅱ-血管紧张素Ⅱ1型受体(ACE-AngⅡ-AT1R)信号通路的调节作用,探讨其防治高血压肾损害的作用机制。方法:选用盐敏感性高血压大鼠(Dahl salt-sensitve,DS)48只,随机数字表法分为低盐组、高盐组、缬沙坦组和补肾降压组,喂食以不同浓度钠盐饲料造模后,予药物干预8周。于干预前后测量血压。干预后酶联免疫吸附测定(ELISA)血清中血肌酐(Cr)、尿素氮(BUN)、血管紧张素Ⅱ(AngⅡ)及转化生长因子-β_(1)(TGF-β_(1))的含量。苏木精-伊红(HE)染色观察肾组织病理学改变情况,Masson染色观察肾纤维化程度。反转录PCR(RT-PCR)及蛋白质印迹法分别检测肾脏血管紧张素转化酶(ACE)及血管紧张素Ⅱ1型受体(AT1R)mRNA及蛋白表达水平。结果:喂食3周不同浓度盐后,喂食高盐各组收缩压均较低盐组升高(P<0.01)。干预后,与低盐组比较,高盐组收缩压升高,Cr、BUN升高,血清AngⅡ及TGF-β_(1)水平升高,HE及Masson染色显示肾脏纤维化程度加重,肾脏ACE及AT1R蛋白及mRNA表达升高(P<0.01)。与高盐组比较,缬沙坦组及补肾降压组收缩压降低,Cr、BUN降低,血清AngⅡ及TGF-β_(1)水平降低,肾脏纤维化程度减轻,肾脏ACE及AT1R蛋白及mRNA表达降低(P<0.05,P<0.01)。结论:补肾降压方有平稳降压,改善肾功能的作用,其作用机制可能与调节ACE/AngⅡ/AT1R轴进而抑制TGF-β_(1)达到延缓肾纤维化相关。

基于血清学指标构建H型高血压患者MACE发生风险预测模型

目的探讨H型高血压患者不良心血管事件(MACE)发生的危险因素,并构建H型高血压患者MACE发生风险预测模型。方法选取2019年1月至2022年11月该院收治的375例H型高血压患者作为研究对象,根据是否发生MACE分为MACE组(41例)和非MACE组(334例)。收集两组临床资料,采用多因素Logistic回归分析H型高血压患者发生MACE的危险因素。构建H型高血压患者MACE发生风险的列线图预测模型,以C-index量化模型预测性能,并绘制校准曲线评价列线图预测模型的校准度及鉴别效度,绘制决策曲线分析列线图预测模型的临床净受益。结果MACE组高血压病程、同型半胱氨酸(Hcy)、尿酸(UA)、Toll样受体(TLR4)水平及靶器官损害数目>2个的患者比例、高血压分级为3级的患者比例、入院当日收缩压(SBP)、入院当日舒张压(DBP)、夜间平均SBP、夜间平均DBP均高于非MACE组,高分子量脂联素(HMW-ADP)水平低于非MACE组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,夜间平均SBP、Hcy、TLR4水平升高及HMW-ADP水平降低均是H型高血压患者发生MACE的危险因素(P<0.05)。列线图预测模型预测H型高血压患者MACE发生风险的C-index为0.821(95%CI:0.712~0.896)。决策曲线分析结果显示,当列线图预测模型预测值为0.75~0.80时,可提供附加临床获益。结论基于Hcy、TLR4、HMW-ADP、夜间平均SBP构建H型高血压患者MACE发生风险的列线图预测模型具有良好预测效果,适合在临床工作中推广应用。

基于UPLC-Q-TOF/MS整合网络药理学探讨平肝益肾方治疗自发性高血压大鼠靶器官损害的效应机制

目的 探究平肝益肾方治疗自发性高血压大鼠靶器官损害的效应机制。方法 使用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF/MS)测定平肝益肾方的化学成分,结合网络药理学方法对平肝益肾方的化学成分进行靶标分析、功能富集,预测平肝益肾方治疗高血压及其靶器官损害的潜在作用机制。将自发性高血压大鼠随机分为模型组、平肝益肾方低剂量组(2 g·kg^(-1))、平肝益肾方高剂量组(5 g·kg^(-1))和缬沙坦组(7.2 mg·kg^-1)),每组6只。Wistar-Kyoto大鼠作为对照组,对照组和模型组大鼠灌胃生理盐水,连续灌胃8周。采用HE和Masson染色,观察大鼠心脏和胸主动脉的病理学损伤和纤维化程度。采用免疫组织化学染色和Western blot检测大鼠心脏、肝脏和肾脏中EGFR的表达水平。采用免疫荧光染色检测大鼠心脏、肝脏和肾脏中EGFR和EEA1共定位情况。结果 通过UPLC-Q-TOF/MS检测出平肝益肾方中的26种化学成分。网络药理学揭示EGFR、PIK3R1和EP300等可能是平肝益肾方治疗高血压及其靶器官损害的关键治疗靶点,平肝益肾方治疗高血压及其靶器官损害可能与EGFR酪氨酸激酶抑制剂耐药性、血脂与动脉粥样硬化和HIF-1信号通路等密切相关。平肝益肾方高剂量组可显著降低大鼠的收缩压和平均动脉压(P<0.05,P<0.01),减轻心脏和胸主动脉的病理学损伤和纤维化程度(P<0.01,P<0.001),显著降低大鼠肝脏和肾脏中EGFR的表达水平(P<0.01),改善肝脏与肾脏的纤维化,显著降低肾脏中EGFR和EEA1的共定位水平(P<0.001),调节EGFR在早期内体的堆积,改善肾脏的纤维化。结论 整合UPLC-Q-TOF/MS、网络药理学和自发性高血压大鼠模型初步探索平肝益肾方治疗高血压及其靶器官损害的效应机制,为平肝益肾方治疗高血压进一步的机制研究和临床应用提供科学依据。

异氟醚通过BMP4/Smad信号通路对自发性高血压大鼠脑损伤的作用机制研究

目的:探究异氟醚通过调节骨发生形态蛋白4(BMP4)及其下游Smad蛋白对自发性高血压大鼠(SHR)脑损伤的作用机制。方法:采用随机数字表法将48只SHR分为模型组、异氟醚组、阳性药物组、异氟醚+LDN193189组,健康大鼠作为健康对照组,每组12只。各组大鼠分别放入氧气箱中,健康对照组、模型组、阳性药物组大鼠通入特殊气体(30%O_(2)、70%N_(2))1 h,异氟醚组、异氟醚+LDN193189组通入混杂2%异氟醚的特殊气体1 h,通过麻醉气体检测仪检测异氟醚含量,确保异氟醚浓度始终保持在2%。通气结束后,异氟醚+LDN193189组大鼠腹腔内注射BMP4/Smad通路抑制剂溶液20μL(LDN193189,5 mg/kg),阳性药物组大鼠腹腔内注射缬沙坦溶液20μL(10 mg/kg),健康对照组、模型组、异氟醚组大鼠腹腔内注射等量的生理盐水。氧气箱通气实验及注射每日1次,持续10 d。无创血压检测仪检测尾动脉收缩压变化;神经学行为评分评价行为功能;脑含水量检测脑水肿程度;原位末端转移酶标记法(TUNEL)染色和尼氏染色观察海马组织病理学变化及神经元损伤情况;荧光定量聚合酶链式反应(PCR)及蛋白免疫印迹(Western Blot)法检测海马组织BMP4、Smad2 mRNA及蛋白表达水平。结果:与模型组比较,异氟醚组、阳性药物组、异氟醚+LDN193189组大鼠海马神经细胞凋亡减少,尼氏小体增多,血压、神经学评分、脑组织含水量显著降低,BMP4、Smad2 mRNA及蛋白表达量显著升高(P<0.05);与异氟醚组比较,异氟醚+LDN193189组大鼠神经细胞凋亡增多,尼氏小体急剧减少,血压、神经学评分、脑组织含水量显著升高,BMP4、Smad2 mRNA及蛋白表达量显著降低(P<0.05);异氟醚组与阳性药物组各项数据差异均无统计学意义(P>0.05)。结论:异氟醚可通过促进BMP4/Smad信号通路减轻SHR脑损伤。

高血压肾损害诊治的中西医研究进展

高血压的发病率在全球日益增多,长期高血压不加以控制会造成多个靶器官的损害,肾脏对维持血压有着重要作用,长期高血压会导致肾小球硬化、缺血,加重肾损害,高血压肾损害不加以控制,会加速终末期肾病的进展,也对社会经济及医疗资源产生负担。中医古籍中没有高血压肾损害的病名记载,但根据高血压肾损害患者所表现出来的蛋白尿、血尿、水肿、头晕等症状,可以归于中医的头痛、眩晕、水肿等范畴,并根据其表现出来的症状进行对症治疗。中西医结合治疗高血压肾损害是目前比较理想的治疗方式,高血压肾损害的西医治疗以降压、降尿蛋白,保护肾功能为主,中医采用辨证论治、多靶点、多途径的个体化的治疗方案。

老年高血压患者诊间血压变异性与靶器官损害的研究

目的回顾性分析老年高血压患者诊间血压变异性及对高血压靶器官的影响。方法选取2015年3月至2022年6月南京医科大学第二附属医院收治的225例老年高血压患者为研究对象,根据WHO老年人年龄划分标准,将患者分为两组,年轻老年人组,年龄60~74岁,共121例;高龄老年人组,年龄≥75岁,共104例。分析两组患者的诊间血压变异特点,并比较两组患者靶器官损害相关指标的差异性。结果年轻老年人组患者肾小球滤过率显著高于高龄老年人组,差异有统计学意义(P<0.05);高龄老年人组尿蛋白、合并慢性肾脏病比例显著高于年轻老年人组,差异有统计学意义(P<0.01);高龄老年人组患者平均收缩压、收缩压标准差、收缩压变异系数、平均舒张压、舒张压标准差、舒张压变异系数均显著高于年轻老年人组,差异有统计学意义(P<0.05);肾功能不全组患者组与肾功能正常组患者的血压指标比较,两组mSBP、mDSP差异具有统计学意义(P<0.05)。结论随着年龄增加,诊间血压变异性升高,且血压水平与肾功能有关。

太仓市某医院高血压病肾损害患者中医证型与肾功能损伤程度分析

目的探究太仓地区高血压病肾损害中医证型与肾功能的关系。方法纳入2021年10月至2022年10月太仓市中医医院(本院)诊治的高血压病肾损害患者363例,根据患者年龄分为青年、中年、老年三组,统计分析不同年龄段中医证型与血压水平、肾功能损伤程度的相关性。结果太仓地区高血压病肾损害中医证型从高到低依次为脾肾两虚、肝肾阴虚、肝阳上亢、痰瘀互结,青年组以肝阳上亢型最多,中年组痰瘀互结型最少,其余各证型之间几乎持平,老年组以脾肾两虚最多,三组脾肾两虚、肝阳上亢占比比较,差异有统计学意义(P<0.05);三组痰瘀互结、肝肾阴虚占比比较,差异无统计学意义(P>0.05)。三组血压比较,差异均有统计学意义(P<0.05)。不同年龄段的肌酐、尿素氮比较,差异均有统计学意义(P<0.05),但肾小球滤过率比较,差异无统计学意义(P>0.05)。不同证型收缩压、舒张压比较,差异均有统计学意义(P<0.05),但肌酐、尿微量白蛋白、24 h蛋白尿定量比较,差异均无统计学意义(P>0.05)。结论本院高血压病肾损害以老年患者为主,证型以脾肾两虚最多,不同年龄、证型在血压、肾功能等方面均存在一定差异,临床应做到因人而异,中青年患者早诊断、早干预,以防治疾病进展,老年患者应更加关注血压、肾功能损害程度。

钩藤降压解郁方对高血压并发抑郁症大鼠学习记忆能力及海马自噬相关蛋白表达的影响

目的研究钩藤降压解郁方(钩藤、天麻、地龙、葛根、丹参等)对高血压并发抑郁症(Hypertension complicated with depression,HD)大鼠学习记忆能力、海马炎症反应和自噬相关蛋白表达的影响。方法将30只自发性高血压大鼠(SHR)随机分为模型组、阳性对照组(苯磺酸左旋氨氯地平0.45 mg·kg^(-1)+盐酸氟西汀1.80 mg·kg^(-1))及钩藤降压解郁方高、中、低剂量组(25.38、12.69、6.34 g·kg^(-1)),另取6只SD大鼠作空白对照组。采用慢性温和不可预见性应激联合孤养的方法干预SHR大鼠,复制HD大鼠模型。造模同时灌胃给药,每天1次,连续6周。采用无创血压计测量大鼠尾动脉收缩压(SBP)和舒张压(DBP);通过Morris水迷宫实验检测大鼠学习记忆能力;透射电镜观察大鼠海马神经元超微结构;ELISA法检测海马组织中白细胞介素1β(IL-1β)、IL-18及IL-10含量;免疫组化法检测海马组织中自噬相关蛋白Beclin1、Bcl-2的表达;Western Blot法检测海马组织中自噬相关蛋白LC3Ⅰ、LC3Ⅱ的表达。结果与空白对照组比较,模型组大鼠第1~6周的SBP、DBP均显著升高(P<0.01);第3、4天的逃避潜伏期显著延长(P<0.01);第1次穿越平台区时间显著延长(P<0.01),穿越平台区次数明显减少(P<0.05),平台区滞留时间显著缩短(P<0.01);海马神经元胞体明显肿胀,嵴破坏,细胞核皱缩,出现大量自噬小体;海马组织中IL-1β、IL-18含量显著增加(P<0.01);海马组织中LC3Ⅱ/LC3Ⅰ蛋白表达比值和Beclin1蛋白表达明显上调(P<0.05,P<0.01),Bcl-2蛋白表达显著下调(P<0.01)。与模型组比较,钩藤降压解郁方低剂量组大鼠第1、3、4、5、6周的SBP显著降低(P<0.01),第1、3、4、5周的DBP明显降低(P<0.05,P<0.01);钩藤降压解郁方中剂量组大鼠第1、5、6周的SBP显著降低(P<0.01),第4周的DBP明显降低(P<0.05);钩藤降压解郁方高剂量组大鼠第1周的SBP显著降低(P<0.01)。钩藤降压解郁方高、中剂量组大鼠第3天的逃避潜伏期明显缩短(P<0.05),钩藤降压解郁方高、低剂量组大鼠第4天的逃避潜伏期明显缩短(P<0.05)。钩藤降压解郁方高、中、低剂量组大鼠第1次穿越平台区时间显著缩短(P<0.01),钩藤降压解郁方中、低剂量组大鼠穿越平台区次数明显增加(P<0.05),平台区滞留时间明显延长(P<0.05)。给药组海马神经元损伤程度减轻,细胞核皱缩情况明显改善,自噬小体减少。钩藤降压解郁方高、中剂量组大鼠海马组织中促炎因子IL-1β、IL-18含量显著降低(P<0.05,P<0.01),钩藤降压解郁方高剂量组大鼠海马组织中抗炎因子IL-10含量显著升高(P<0.01)。钩藤降压解郁方高、中、低剂量组海马组织中的LC3Ⅱ/LC3Ⅰ蛋白表达比值显著下调(P<0.01),Bcl-2蛋白表达显著上调(P<0.01);钩藤降压解郁方高、中剂量组大鼠海马组织中Beclin1蛋白表达明显下调(P<0.05,P<0.01)。结论钩藤降压解郁方可降低HD大鼠尾动脉压,改善其学习记忆能力,缓解海马神经元损伤,其机制可能与减少促炎因子释放,提高抗炎因子水平,调控海马自噬相关蛋白LC3Ⅱ/LC3Ⅰ、Beclin1和Bcl-2的表达有关。

NAD^(+) exhaustion by CD38 upregulation contributes to blood pressuree elevation and vascular damage in hypertension

Hypertension is characterized by endothelial dysfunction and arterial stiffness,which contribute to the pathogenesis of atherosclerotic cardiovascular diseases.Nicotinamide adenine dinucleotide(NAD^(+))is an indispensable cofactor in all living cells that is involved in fundamental biological processes.However,in hypertensive patients,alterations in NAD^(+)levels and their relation with blood pressure(BP)elevation and vascular damage have not yet been studied.

高血压早期肾损害诊断指标的筛选

目的:筛选高血压早期肾损害的诊断指标。方法:搜集2020年1月至2023年2月河南省人民医院内科病房收治的高血压患者,选取高血压早期肾损害[30 mg/24 h≤尿白蛋白排泄率(uAER)<300 mg/24 h]患者51例(肾损害组),以及单纯高血压患者51例(对照组)。比较两组患者血清尿素氮(BUN)、肌酐(SCr)、同型半胱氨酸(HCY)、视黄醇结合蛋白(RBP)、胱抑素C(CysC)、尿微量白蛋白(umALB)、微量白蛋白/肌酐比值(uACR)、α1微球蛋白(uα1MG)、β2微球蛋白(uβ2MG)、N-乙酰-β-D氨基葡萄糖苷酶(uNAG)及转铁蛋白(uTF)水平的差异。绘制ROC曲线,比较上述指标对高血压早期肾损害的诊断效能。结果:肾损害组患者血清BUN、SCr、HCY、RBP、CysC水平及umALB、uAER、uACR、uα1MG、uβ2MG、uNAG、uTF水平均高于对照组(P均<0.05)。ROC曲线AUC>0.9的指标从高到低分别为uACR>CysC>uα1MG>uβ2MG>umALB>RBP,其中CysC+uACR联合诊断的效能和敏感度最高[AUC(95%CI)为0.994(0.954~1.000),敏感度为1.000]。结论:CysC+uACR为高血压患者早期肾损害的高效诊断指标。

Association of blood pressure variability with target organ damage in older patients with essential hypertension

Background:Although multiple measures of blood pressure variability(BPV)have been proposed,whether they are better than mean blood pressure in predicting target organs is unclear.We aimed to determine the relationship between short term BPV and target organ injury.Methods:This study was a retrospective study,and 635 inpatients in the Department of Cardiology from 2015 to 2020 were selected.We divided participants into four groups on the basis of the quartiles of BPV.One-way analysis of variance was used to compare the differences between the groups,and linear regression was used to analyze the relationship between BPV and target organ damage.Results:The average age of 635 patients was 74.36±6.50 years old.Among them,354 of 627 patients had diminished renal function(56.5%),221of 604 patients had associated left ventricular hypertrophy(36.6%),and 227 of 231 patients had carotid plaque formation(98.3%).The baseline data indicated significant differences in fasting glucose,total cholesterol,low-density lipoprotein,creatinine,glomerular filtration rate,sex,calcium channel blocker use,and the rate of diminished renal function.Multiple linear regression analysis showed that BPV was negatively correlated with renal injury(creatinine:r=0.306,p<0.01;estimated glomerular filtration rate:r=0.058,p<0.01),and BPV is positively correlated with cardiac injury(r=0.083,p<0.01).Elevated BPV was not found to be associated with vascularinjury.Conclusion:Renal function decreases with increasing BPV and left ventricular mass increases with increasing BPV.

云南省高血压患者外周血管损伤的影响因素分析

目的探讨云南省高血压患者外周血管损伤的影响因素。方法选取2021年1月—2021年12月参与云南省《中国居民心血管病及其危险因素监测》项目并诊断为高血压行四肢血压监测的1828例患者为研究对象。根据臂踝脉搏波传导速度(baPWV)是否≥1800mm/s将对象分为动脉硬化组(AS组)和非动脉硬化组(非AS组),分别有522、1306例。采集患者的年龄、体质量指数(BMI)、腰围、吸烟、饮酒、饮茶、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、尿酸(UA)、肌酐(Cr)、糖化血红蛋白(HbA1c)、葡萄糖(GLU)、血浆肾素浓度(PRC)、血浆醛固酮浓度(PAC)、醛固酮/肾素(ARR)、尿微量白蛋白(UALB)、尿肌酐(Ucr)、尿微量白蛋白/尿肌酐(ACR)、baPWV。采用多因素一般Logistic回归模型分析高血压患者外周血管损伤的影响因素。结果AS组男性比例、BMI、吸烟、饮茶、DBP较非AS组低(P<0.05),年龄、糖尿病、收缩压(SBP)、较非AS组高(P<0.05)。两组饮酒、腰围比较,差异均无统计学意义(P>0.05)。AS组HbA1C、GLU、HDL-C、LDL-C、TC、Cr、UALB、ACR较非AS组高(P<0.05),Ucr、PRC较非AS组低(P<0.05)。两组TG、UA、PAC、ARR比较,差异无统计学意义(P>0.05)。多因素一般Logistic回归分析结果显示:年龄[OR=1.103(95%CI:1.087,1.120)]、平均SBP[OR=1.035(95%CI:1.024,1.045)]和Cr[OR=1.007(95%CI:1.002,1.012)]是导致外周血管损伤的危险因素(P<0.05)。结论年龄、平均SBP、Cr指标升高可加重高血压患者血管损伤的发生、发展。