The Effectiveness of Albumin Combined with Diuretics in Treating Ascites in Cirrhosis

Cirrhosis often leads to various complications during its progression,with ascites being one of the most common.Among these cases,5%to 10%are classified as refractory ascites.In recent years,clinical research on the treatment of cirrhotic ascites has yielded increasingly enriched results.In this paper,a large number of clinical data on the treatment of ascites using albumin combined with diuretics were collected,and it was found that there were more results in group control studies.It was believed that albumin combined with diuretic therapy could effectively improve symptoms,reduce the occurrence of adverse reactions,ensure the safety of patients,and have a good clinical application prospect.This paper reviews the efficacy of albumin combined with diuretics in the treatment of ascites in cirrhosis.

Effects of Different Diuretics on Water Drinking Amount, Urination Volume and Related Blood Indices of Sheep Fed with Cottonseed

[Objective] This study aimed to investigate the effects of three kinds of diuretics on the water drinking amount and urination volume of sheep fed with cottonseed hulls. [Method] The method of self-control was adopted. Five two-year-old male Kazak sheep about 40 kg which never had intake of the feeds containing gossypol were selected. The experiment was divided into five periods, namely the control period, a period with the supplement of 300 mg/d of hydrochlorothiazide, a period with the supplement of 200 mg/d of hydrochlorothiazide, a period with the supplement of 350 mg of GY-01 and a period with the supplement of 200 mg of GY-01. The sheep were fed with the concentrate and the cottonseed hulls in the control period, and corresponding diuretics were supplemented in the rest four periods. The water drinking amount, urination volume and the contents of the hormone and ion in the blood were determined in each period. [Result] After 350 mg GY-01 was supplemented, the water drinking amount of each sheep had an increase of 60.14% compared with that of the sheep in the control period and the urination volume was 2.67 times of that of the latter, and the differences were both significant （P0.01）. The antidiuretic hormone declined by 32.59% compared with that of the sheep in the control period, with the significant difference （P 0.05）. The adrenocorticotropic hormone content increased by 81.93% compared with that of the sheep in the control period and the difference was significant （P0.01）. An increase of 28.04% （P 0.05） and 39.39% （P 0.01） was found in the contents of serum potassium and phosphorus respectively compared with that of sheep in the control period. [Conclusion] The diet with supplement of GY-01 can increase the urination volume of livestock fed with the cottonseed hulls, and the most appropriate supplement amount is 200 mg GY-01.

Ototoxic effects and mechanisms of loop diuretics

Over the past two decades considerable progress has been made in understanding the ototoxic effects and mechanisms underlying loop diuretics. As typical representative of loop diuretics ethacrynic acid or furosemide only induces temporary hearing loss, but rarely permanent deafness unless applied in severe acute or chronic renal failure or with other ototoxic drugs. Loop diuretic induce unique pathological changes in the cochlea such as formation of edematous spaces in the epithelium of the stria vascularis, which leads to rapid decrease of the endolymphatic potential and eventual loss of the cochlear microphonic potential, summating potential, and compound action potential. Loop diuretics interfere with strial adenylate cyclase and Nat/Kt-ATPase and inhibit the Na-K-2Cl cotransporter in the stria vascularis, however recent reports indicate that one of the earliest effects in vivo is to abolish blood flow in the vessels supplying the lateral wall. Since ethacrynic acid does not damage the stria vascularis in vitro, the changes in Nat/Kt-ATPase and Na-K-2Cl seen in vivo may be secondary effects results from strial ischemia and anoxia. Recent observations showing that renin is present in pericytes surrounding stria arterioles suggest that diuretics may induce local vasoconstriction by renin secretion and angiotensin formation. The tight junctions in the blood-cochlea barrier prevent toxic molecules and pathogens from entering cochlea, but when diuretics induce a transient ischemia, the barrier is temporarily disrupted allowing the entry of toxic chemicals or pathogens.

The use of diuretics in acute heart failure: Evidence based therapy?

The evidence base for the use of diuretics in acute heart failure is limited, with no large double-blind placebo-controlled randomized trials. However, their use as a first line treatment of acute heart failure is firmly established in clinical practice, and endorsed in clinical guidelines. Loop diuretics are typically the first line diuretic strategy for the treatment of acute heart failure. For patients with considerable fluid retention, there is some evidence that initial treatment with continuous infusion or boluses of high dose loop diuretic is superior to an initial lower dose strategy. In patients who are diuretic resistant, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. Intravenous low-dose dopamine has also been used to assist diuresis and preserve renal function in such circumstances, but trials are underway to confirm the clinical value of this agent. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence base is not secure, and its place in clinical practice is yet to be established.

Determination of 8 Diuretics and Probenecid in Human Urine by Gas Chromatography-Mass Spectrometry: Confirmation Procedure

A fast and sensitive method for determination of 8 diuretics (acetazolamide, bendroflumethiazide, bumetanide, chlorthalidone, furosemide, hydrochlorothiazide, metolazone, triamterene) and masking agent (probenecid) in human urine using gas-chromatography with mass spectrometric detection is described. The extraction of the substances as function of the nature of organic solvent, mixing time and pH of aqueous phase was studied. The tandem mass spectrometry was used to increase selectivity of diuretics determination due to elimination of background interferences. Fragmentation reactions were studied for each compound and their collision energies were optimized to obtain the best selectivity. The results of method’s validation demonstrate its suitability in routine analysis for confirmation purposes.

The Effect of Loop Diuretics on Sarcopenia and Long-Term Prognosis in Patients with Refractory Hepatic Ascites Treated with Tolvaptan

We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese version of the Support Team Assessment Schedule. The psoas muscle index (PMI) was used to define sarcopenia. A statistically significant difference was observed in the PMI between patients receiving low-dose (3.6 ± 1.2 cm2/m2) and high-dose furosemide (3.1 ± 1.2 cm2/m2) before tolvaptan treatment (P = 0.048). The PMI increased from 3.2 ± 1.1 cm2/m2 to 3.5 ± 1.3 cm2/m2 (P = 0.002) in responders, but decreased from 3.4 ± 1.2 cm2/m2 to 3.0 ± 1.0 cm2/m2 (P = 0.106) in non-responders before and after tolvaptan treatment, respectively. The long-term prognosis improved in responders compared with non-responders (mean survival time: 646 days vs. 228 days, P < 0.001). Early introduction of tolvaptan treatment is necessary to prevent the progression of sarcopenia.

Urea transporter inhibitors identified as novel diuretics

Urea transporters （UT）, including isoforms of UT-A endothelia and erythrocytes, play an important role in the urine in kidney tubule epithelia and UT-B in vasa recta concentration mechanism by mediated an intrarenalurea recycling, suggesting that functional inhibition of these proteins could have therapeutic use as diuretic. By in- tegrated cell based high throughput screening and in silico methods, a class of small-molecule drug-like compounds with thienoquinolin core structure was found to have inhibition activity on both UT-A and UT-B. The structure and activity relationship analysis showed a compound PU-48, named chemically as methyl 3-amino-6-methoxythieno[ 2, 3-b] quinoline-2-carboxylate, had the best UT-A and UT-B inhibition activity. IC50s of PU-48 on UT-B facilitated as determined by erythrocyte lysis assay. In vivo urea transport were micromole level in human, rat, and mouse, activity of PU-48 on urinary concentrating function was evaluated in rats fed ad libitum in metabolic cages. Urine output significantly increased in a dose-dependent manner in rats subcutaneously administered PU-48. Urinary os- molality and urea concentration were significantly decreased. The peak changes of urine output, urinary osmolality and urinary urea concentration occurred between 2 and 4 h after PU/18 administration, with values returning to was subcutaneously injected every 6 h the 24 h urine output in baseline by 10 h. When PU-48 at 50 mg · kg^-1 PU-48 treated rats was significantly higher than that in vehicle control rats. Urinary osmolality and urea concentra- tion in PU-48 treated rats were significantly lower than in vehicle control rats. The excretion of Na ＋ , K ＋ , C1- was PU-48 treated rats had significantly higher urea excre- similar in PU-48 treated and vehicle control rats. However, tion than vehicle control rats. The data suggest that PU-48 caused a urea-selective diuresis without disturbing elec- TGs, and LDL-C in PU-48-treated rats were similar with those trolyte metabolism. Notably, blood urea, T-CHO, in vehicle control rats, which are normal levels. These data indicate that the diuretic effect of PU-14 does not cause electrolyte imbalance and abnormal metabolism. It is predicated that UT inhibitors have potential clinical applica- tions as sodium-sparing diuretics in edema from different etiologies, such as congestive heart failure and cirrhosis.

GC-MS STUDY ON DIURETICS IN URINE Ⅰ.BETECTION METHOD USING METHYLATION

A reliable and sensitive method is developed for the detection of common diuretics in human urine. diuretics along with probenecid are methylated and subjected to GC-MS analysis.Both chromatographic and mass spectrometric data are obtained in selected ion monitoring and full scanning modes.The average detection limit is 0.1-1.0 ag/mi urine.This method is suitable to large-scale and routine screening or confirmation of diuretics in doping control.

GC-MS STUDY ON DIURETICS IN URINE Ⅱ.DETECTION METHOD USING TRIMETHYLSILYLATION

A reliable method is described for the detection of amitoride,triamterene. canrenone and spironolactone in human urine using GC-MS analysis after trimethytsitytation.The mass spectrometric and metabotic features of the compounds are discussed

Effects of Three Commonly-used Diuretics on the Urinary Proteome

Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics （furosemide, F; hydrochlorothiazide, H; and spirolactone, S） on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography-tandem mass spectrometry （LC-MS/MS）. Based on the criteria of P ≤ 0.05, a fold change ≥2, a spectral count ≥ 5, and false positive rate （FDR） ≤1%, 14 proteins （seven for F, five for H, and two for S） were identified by Progenesis LC-MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.

Discovery of novel diarylamides as orally active diuretics targeting urea transporters

Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.

芪苈强心胶囊降低慢性心力衰竭急性失代偿患者发生利尿剂抵抗风险的回顾性研究

背景利尿剂抵抗与心力衰竭(HF)患者的病死率增加有关。芪苈强心胶囊是用于治疗HF的中药。目前缺乏其在改善利尿剂抵抗方面作用的临床证据。目的探讨芪苈强心胶囊能否降低慢性HF急性失代偿(ADCHF)患者发生利尿剂抵抗的风险并改善其预后。方法纳入2018年1月—2022年6月在天津大学胸科医院CICU病区住院治疗的HF患者374例为研究对象,根据是否发生利尿剂抵抗将患者分为利尿剂抵抗组(118例)和非利尿剂抵抗组(256例)。收集患者的一般资料和实验室检查结果等。对患者随访12个月,观察因心血管事件再住院或全因死亡情况。绘制各组患者的Kaplan-Meyer生存曲线,生存曲线比较采用Log-rank检验。采用多因素Logistic回归分析探究患者发生利尿剂抵抗风险的影响因素。采用多因素Cox回归分析探究ADCHF患者发生终点事件的影响因素。结果利尿剂抵抗组年龄、体质量、N末端前体脑利钠肽(NT-proBNP)、血尿素氮、血肌酐、血尿酸、国际标准化比值(INR)高于非利尿剂抵抗组,24 h液体摄入量、估算肾小球滤过率(eGFR)、淋巴细胞绝对值、芪苈强心胶囊使用率低于非利尿剂抵抗组。多因素Logistic回归分析结果显示,使用芪苈强心胶囊(OR=0.363,95%CI=0.186~0.708,P=0.003)、24 h液体摄入量升高(OR=0.286,95%CI=0.177~0.461,P<0.001)是ADCHF患者发生利尿剂抵抗风险的保护因素。体质量增加(OR=1.064,95%CI=1.040~1.088,P<0.001)、血尿酸增高(OR=1.002,95%CI=1.000~1.004,P=0.027)是患者发生利尿剂抵抗风险的危险因素。Log-rank检验结果显示,利尿剂抵抗组无终点事件平均生存时间短于非利尿剂抵抗组(χ^(2)=11.866,P=0.001);未使用芪苈强心胶囊患者无终点事件平均生存时间短于使用芪苈强心胶囊患者(χ^(2)=6.502,P=0.011)。多因素Cox回归分析结果显示,使用芪苈强心胶囊(HR=0.536,95%CI=0.308~0.933,P=0.027)和使用血管紧张素受体脑啡肽酶抑制剂/血管紧张素转化酶抑制剂/血管紧张素受体阻滞剂(HR=0.435,95%CI=0.229~0.826,P=0.011)是患者发生终点事件的保护因素,总胆红素升高(HR=1.019,95%CI=1.008~1.030,P=0.001)、总胆汁酸升高(HR=1.029,95%CI=1.002~1.058,P=0.036)是患者发生终点事件的危险因素。结论在常规抗HF治疗的基础上使用芪苈强心胶囊可以降低ADCHF患者发生利尿剂抵抗的风险,同时降低这类患者1年内因心血管事件再住院或全因死亡的风险。

Congestive Heart Failure: Treatment of Symptoms or Causes

This paper is based on the author’s 20+ years of experience treating patients with congestive heart failure (CHF) as a cardiologist. In the 20+ years, 64 patients were treated, including both with reduced and preserved left ventricular function. Most patients had a 4 - 5 days hospitalization in their first admission with one readmission (1.6%) over seven years. This paper will help us understand the physiology and pathophysiology of congestive heart failure, especially how to use beta blockers and diuretics. It will shorten the length of hospitalization and lower the readmission rate and cost of CHF treatment. This paper will help us to open another research direction for CHF.

Prognostic Factors in Cardiorenal Syndrome Type 1: Retrospective Observational and Analytical Study

Introduction: Type 1 cardiorenal syndrome (CRS 1) is characterized by acute impairment of cardiac function leading to acute renal dysfunction. CRS1 is present in 25% of patients admitted for heart failure. The objective of our study is to analyze the epidemiological, clinical, therapeutic profile and the risk and prognostic factors of these patients. Materials and Methods: We identified 120 patients with cardiorenal syndrome (CRS) over a one-year period to determine the prevalence and risk factors for developing CRS 1. We analyzed the clinical, biological, and evolutionary profiles of patients with CRS 1 and determined the risk factors for the occurrence of acute kidney injury (AKI) as well as the mortality factors in these patients. Résultats: The average age of our patients with CRS1 is 58 ± 9 years, with a sex ratio of 1.4. The average eGFR of our patients is 35 ± 6.5 ml/min/1.73m2. Diabetes was found in 17% of our patients and hypertension in 14%. The etiology of cardiac impairment is predominantly acute coronary syndrome (ACS), followed by rhythm disorders. Renally, all our patients have acute kidney injury (AKI), with 86% having functional acute renal failure and 14% having acute tubular necrosis. Therapeutically, 50% of our patients are on diuretics, 42% receive beta-blocker treatment, and RAAS blockers are used in 29% of cases. Renal replacement therapy (RRT) sessions were required in 13.8% of cases. In univariate analysis, male gender, tachyarrhythmia, and hypertension are associated with the early onset of acute kidney injury (AKI). The use of diuretics, anemia, and low left ventricular ejection fraction (LVEF) are linked to a higher risk of developing CRS 1 (p = 0.021, p = 0.037, p = 0.010 respectively). In multivariate analysis, advanced age is significantly associated with increased mortality risk in CRS 1 patients (p = 0.030), while beta-blocker use is considered a protective factor (p = 0.014). Conclusion: Our study identifies several key factors associated with outcomes in type 1 CRS. Male gender, tachyarrhythmia, and hypertension are linked to early-onset AKI. The use of diuretics and the presence of anemia increase the risk of developing CRS1. Advanced age is significantly associated with higher mortality rates. Conversely, the use of beta-blockers appears to be protective in this patient population. .

参芪益心汤治疗心力衰竭合并利尿剂抵抗患者的临床疗效及对其心功能、NT-proBNP水平的影响

目的 探讨参芪益心汤加减治疗心力衰竭合并利尿剂抵抗患者的疗效。方法 选取2021年12月—2022年12月期间黑龙江中医药大学附属第一医院收治的心力衰竭合并利尿剂抵抗患者100例作为研究对象,按照随机数字表法分为对照组和试验组,每组各50例。对照组予常规治疗,试验组在对照组基础上加用参芪益心汤,两周为1个疗程,两组患者均治疗4周。观察比较两组患者治疗前后心功能指标[左心室舒张末期内径(Left ventricular end-diastolic diameter,LVDD)、左房内径(Left atrial diameter,LAD),计算左室射血分数(Left ventricular ejection fraction,LVEF)]、血清指标[N端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)、肌钙蛋白T(Cardiac troponin T,CTnT)、肌酸磷化脢同功脢(Creatine kinase isoenzyme,Ck-MB)]、中医证候积分,比较两组患者临床疗效及不良反应。结果 治疗后两组患者心功能LVDD、LAD水平均较治疗前降低,LVEF水平均较治疗前升高,差异有统计学意义(P<0.05);且试验组LVDD、LAD水平均明显低于对照组,LVEF水平明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者NT-proBNP、CTnT、Ck-MB水平均较治疗前降低,差异有统计学意义(P<0.05);且试验组NT-proBNP、CTnT、Ck-MB水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者心悸、气短、气喘、胸闷评分均较治疗前降低,差异有统计学意义(P>0.05);且试验组心悸、气短、气喘、胸闷评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后试验组总有效率96.00%(48/50)高于对照组72.00%(36/50),差异有统计学意义(P<0.05)。治疗期间,两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论 应用参芪益心汤能够显著改善心功能,缓解临床症状,疗效显著,值得临床应用。

连续性肾脏替代疗法对难治性心力衰竭伴利尿药抵抗患者预后的影响

目的探讨连续性肾脏替代疗法(continuous renal replacement therapy,CRRT)对难治性心力衰竭(refractory heart failure,RHF)伴利尿药抵抗患者预后的影响,分析其影响因素。方法选取北京市普仁医院2019年1月至2022年1月收治的利尿药抵抗性RHF患者102例开展回顾性研究。患者均采用CRRT治疗,比较患者治疗前、后的左心室射血分数(left ventricular ejection fraction,LVEF)、心脏指数(cardiac index,CI)、心排血量(cardiac output,CO),检测血清氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)、血肌酐(serum creatinine,Scr)、尿酸(uric acid,UA)、血尿素氮(blood urea nitrogen,BUN)浓度,并记录24 h尿量变化。观察患者28 d的预后情况,根据预后分成生存组、死亡组,收集并比较两组患者的临床资料,利用多元Logistic回归模型分析CRRT治疗患者预后的影响因素。结果经治疗后,患者LVEF、CI、CO高于治疗前,血清NT-proBNP浓度低于治疗前,差异有统计学意义(P<0.05)。患者治疗后的血清Scr、UA、BUN浓度低于治疗前,而24 h尿量高于治疗前,差异有统计学意义(P<0.05)。102例患者中病死率为35.29%,生存率为64.71%。死亡组入院后6 h内治疗占比为13.89%,低于生存组的40.91%,且死亡组入院时平均动脉压(mean arterial pressure,MAP)、血红蛋白(hemoglobin,Hb)浓度及24 h尿量低于生存组,血清NT-proBNP浓度高于生存组,差异有统计学意义(P<0.05)。多元Logistic回归分析显示,患者入院后6 h内接受治疗及入院时相对较高的MAP、Hb浓度及24 h尿量是预后保护性因素,入院时血清NT-proBNP浓度过高是预后危险因素(P<0.05)。结论CRRT对利尿药抵抗性RHF患者有一定治疗作用,但早期病死率仍较高,且CRRT治疗的预后与多种因素相关,临床需引起重视。

真武汤加减治疗慢性心力衰竭合并利尿剂抵抗的Meta分析

目的系统评价真武汤加减联合西药常规治疗慢性心力衰竭(Chronic heart failure,CHF)合并利尿剂抵抗(Diuretic resistance,DR)的临床疗效。方法检索自建库起至2023年11月1日中国知网、万方数据库、维普数据库、中国生物医学文献数据库、PubMed、Cochrane Library、Embase、Web of Science、Clinical Trials、中国临床试验注册中心等数据库中真武汤加减治疗CHF合并DR的随机对照试验,采用Review Manager 5.4软件对文献数据进行Meta分析。结果共纳入15篇文献,包括1187例患者。Meta分析结果显示,与单纯西药对照组相比,真武汤加减联合西药常规治疗组患者在24 h总尿量[n=1058,MD=397.30,95%CI(269.44,525.16),P<0.01]、临床总有效率[n=625,RR=1.24,95%CI(1.15,1.34),P<0.01]、左心室射血分数(Left ventricular ejection fractions,LVEF)[n=697,MD=4.32,95%CI(2.51,6.112),P<0.01]、氨基末端脑利钠肽前体(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平[n=282,MD=734.4,95%CI(828.93,639.87),P<0.01]、外周血IL-6水平[n=170,MD=-5.70,95%CI(-7.23,-4.16),P<0.01]、外周血TNF-α水平[n=170,MD=-12.79,95%CI(-15.53,-10.04),P<0.01]方面均有明显改善,而左室舒张末内径未见明显改善[n=266,MD=-4.50,95%CI(-9.36,0.35),P=0.07]。药物安全性良好,加载中药治疗可显著降低低钾血症发生率[n=177,RR=0.32,95%CI(0.18,0.57),P<0.01]。结论在单纯西药治疗基础上,予真武汤加减可改善CHF合并DR患者24 h尿量、提高临床总有效率、改善患者心功能、降低炎症因子水平,且安全性较好。

从三焦理论探讨恶性胸腹腔积液的治疗

恶性胸腹腔积液病机为三焦阻滞,水饮内停,元气运行受阻,血液凝滞,痰瘀内结,治疗应在行气利水、淡渗利湿或峻下逐水、逐瘀利水通利三焦的基础上,兼顾肺、脾,肾三脏的功能失调。通利三焦多为宣上通下的行气利水药物,如柴胡、枳实、桔梗等,同时配以淡渗利湿药物或者峻下逐水药物以通调水道,如茯苓、猪苓、泽泻等,尚需加用利水逐瘀药物,如水蛭、桃仁、泽兰等。兼顾肺、脾,肾三脏的功能失调,分别以开宣肺气、健脾益气、温补肾阳之法,开宣肺卫通利三焦用以麻黄为基础的方药如越婢汤、越婢加术汤、甘草麻黄汤及大小青龙汤;健脾渗湿疏利三焦用以黄芪为基础的方药如防己茯苓汤、桂枝加黄芪汤、桂枝苦酒汤;温补肾阳用附子,干姜。同时尚需要考虑恶性肿瘤癌毒这一主要病理因素,加用祛除癌毒之邪药物如山慈菇、蛇六谷、全蝎等。

基于大鼠尿液生物标志物探析冬葵果醇提物的利尿作用

目的:采用尿液代谢产物分析方法评价冬葵果醇提物利尿作用机制。方法:选取50只雄性SD大鼠随机分为正常组(Z组),冬葵果醇提物高剂量组(DG组)、冬葵果醇提物中剂量组(DZ组)、冬葵果醇提物低剂量组(DD组),阳性对照组(Y组)。制备大鼠水负荷模型后置代谢笼收集0~1、1~2、2~4、4~6、6~24 h范围内尿液;按照试剂盒要求检测尿液K+、Cl−、Na+及血清ADH、ANP、ALD、cAMP、cGMP、AQP1和AQP2的含量;采用代谢组学方法检测尿液中内源性代谢产物,并进行代谢差异表征,查寻尿液中差异代谢产物。结果:与Z组比较,Y组0~1、1~2、2~4 h三个时间段的尿量明显增加,差异有统计学意义(P<0.05,P<0.01);DD组2~4 h和6~24 h两个时间段的尿量明显增加,差异有统计学意义(P<0.05,P<0.01);DZ组和DG组2~4、4~6 h两个时间段的尿量明显增加,差异有统计学意义(P<0.05)。与Y组比较,DD组、DZ组和DG组0~1、1~2 h两个时间段尿量明显降低,差异有统计学意义(P<0.05)。与Z组比较,冬葵果醇提物各剂量组能显著升高尿液Na+和Cl-含量,差异有统计学意义(P<0.01)。与Y组比较,DG组Cl-含量显著升高,DZ组和DD组Na+、Cl-含量显著升高,差异有统计学意义(P<0.05)。与Z组比较,DG组ANP和AQP2含量显著升高、ADH含量显著下降,差异有统计学意义(P<0.05);DD组cAMP和AQP1含量显著升高,差异有统计学意义(P<0.05)。与Y组比较,DG组ADH含量显著降低,ANP含量显著升高,差异有统计学意义(P<0.05)。代谢组学分析显示,与Z组比较,尿液样本中共筛选得出DD组6个、DZ组8个、DG组10个差异代谢物,这些代谢物水平存在明显的变化。结论:羟脯氨酸、葡萄糖酸和儿茶酚是参与冬葵果醇提物利尿作用机制的尿液生物标志物。