Increased expression of profibrotic neutral endopeptidase and bradykinin type 1 receptors in stenotic aortic valves.

AIMS: In aortic stenosis (AS), adverse remodelling of the valves may depend on altered local regulation of pro- and antifibrotic systems. We have recently shown that angiotensin-converting enzyme (ACE), which generates profibrotic angiotensin II and inactivates antifibrotic bradykinin (BK), is upregulated in stenotic aortic valves. Here, we analyse the expression of neutral endopeptidase (NEP), another profibrotic and BK-degrading enzyme, and of BK receptors in aortic valves in AS. METHODS AND RESULTS: Stenotic aortic valves (n = 86) were obtained at valve replacement surgery and control valves (n = 13) at cardiac transplantation. Expression levels of NEP and BK type 1 and 2 receptors (BK-1R and BK-2R) in aortic valves and in isolated valvular myofibroblasts were analysed by real-time PCR and immunohistochemistry, and NEP activity was quantified by autoradiography. NEP, BK-1R, and BK-2R mRNA levels were higher in stenotic than in non-stenotic valves (P < 0.05 for each) and the respective proteins localized to valvular endothelial cells and myofibroblasts. In stenotic valves, the proteolytic activity of NEP was significantly increased (4.5-fold, P < 0.001), and tumour necrosis factor-alpha induced the expression of NEP in cultured myofibroblasts. Finally, treatment of cultured myofibroblasts with an NEP inhibitor (phosphoramidon) downregulated the expression of profibrotic transforming growth factor-beta1, whereas addition of BK decreased the expression of collagens I and III which was reversed by a BK-2R antagonist. CONCLUSION: NEP activity is increased in stenotic aortic valves in parallel with increased expression of BK-receptors. The upregulation of NEP and BK-1R have the potential to promote valvular fibrosis and remodelling while the increase in BK-2R may represent a compensatory antifibrotic response. These findings add novel pathogenic insight and raise potential new therapeutic targets in AS.     

Ejection fraction-velocity ratio for the assessment of aortic bioprosthetic valves in patients with systolic dysfunction

BACKGROUND:

The continuity equation (CE) represents the ‘gold standard’ for the evaluation of aortic valve area in patients with aortic stenosis, but it is time-consuming and subject to error, and can be technically demanding. Recently, a new echocardiographic nonflow corrected index was introduced and demonstrated excellent accuracy in quantifying the effective orifice area (EOA) in native aortic valves and bioprostheses. This new index, the ejection fraction (EF)-velocity ratio (EFVR), is obtained by dividing the percentage left ventricular EF by the maximum aortic gradient.

OBJECTIVE:

To assess the usefulness of this echocardiographic index for quantifying the EOA in patients with aortic bioprosthesis and left ventricular dysfunction.

METHODS:

A total of 70 patients (25 women and 45 men) with aortic bioprosthesis and left ventricular dysfunction (EF of 49% or less) were studied. The mean (± SD) age of the study population was 71.4±9 years. The EOA was evaluated, both by the CE and by the EFVR.

RESULTS:

A significant linear correlation between the CE and the EFVR was found (r=0.80; P<0.0001). The receiver operating characteristic curve analysis showed good agreement between the CE and the EFVR. An EFVR value of 1.15 or less was found to have a good sensitivity (89%) and good specificity (91%) in identifying patients with an EOA of 1.0 cm² or smaller, with positive and negative predictive values of 79% and 95%, respectively.

CONCLUSIONS:

The EFVR, a simple index that is less time-consuming than the CE, allows the identification of patients with aortic bioprosthesis stenosis with excellent sensitivity and specificity. It may be taken into consideration in clinical practice for the evaluation of patients with aortic bioprosthesis stenosis and left ventricular dysfunction.     

A role of mast cells for hepatic fibrosis in primary sclerosing cholangitis.

We encountered four patients with overt primary sclerosing cholangitis (PSC) which were histologically classified into stage 2 or 3. We examined the expression of stem cell factor (SCF), a ligand of c-kit, in injured bile ducts by immunohistochemistry, and mast cells were identified by immunohistochemistry using anti-HMCT (human mast cell tryptase) and anti-c-kit antibodies to clarify their relation with portal fibrosis coincident with destroyed bile ducts. SCF was detected in the epithelia of most bile ducts in PSC, and many HMCT- and c-kit-positive mast cells were found in portal tracts. Image analysis showed more significant numbers of c-kit-positive mast cells per area of portal tract in PSC than in chronic hepatitis C, and they might increase from stage 2 to 3. c-Kit-positive cells infiltrated into the portal tracts with SCF-positive destroyed bile ducts, and c-kit mast cells should be investigated in detail to make a role for portal fibrosis in PSC.     

Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors.

AIMS: Aortic valve diseases are characterized by pathological remodelling of valvular tissue but the cellular and molecular effectors involved in these processes are not well known. The role of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 are investigated here. METHODS AND RESULTS: Histological analysis of pathological valves [aortic stenosis (AS) (n=49), aortic regurgitation (AR) (n=23)] and control valves (n=8) was performed. The main tissue abnormalities (calcification, inflammatory cells, and capillaries) observed in AS were less severe or absent in AR. However, both groups of pathological valves displayed similar histological signs of extracellular matrix (ECM) remodelling. Biochemical analysis of MMPs and TIMPs (gelatin and casein zymography and ELISA) was performed on valve extracts. MMP-2 activity was not significantly different in control and pathological valves. Increases in MMP-9 and MMP-3 in AS demonstrated an inflammatory state. Finally, there was a four- to seven-fold increase of TIMP-1 in pathological valves. TIMP-1, TIMP-2, and MMP-2 were synthesized by the valvular interstitial cells in primary culture. CONCLUSION: This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.     

Use of the stiff shaft,straight terumo glidewire in crossing stenotic aortic valves

One of the more difficult and time-consuming diagnostic procedures in the cardiac catheterization laboratory is retrograde crossing of the severely stenotic aortic valve. Whereas patients with advanced aortic stenosis tend to be complicated and elderly, lengthy procedures can lead to a higher incidence of thrombo-embolic and vascular complications and relatively greater procedural blood loss. This report concerns the use of the Terumo Glidewire to facilitate passage through stenotic and tortuous peripheral arteries. © 1993 Wiiey-Liss, Inc.     

Effect of Acetaldehyde Upon Cathepsin G and Chymase. NRAS Implications

Hypertension is commonly observed in alcoholics. Both the renin-angiotensin system (RAS) and the non-renin-angiotensin system (NRAS) have been implicated in the dynamics of blood pressure maintenance. In bilaterally nephrectomized rats, acetaldehyde has been reported to enhance the generation of the rate-limiting angiotensin I (ANG I) in the plasma, and in humans it inhibits the activity of several angiotensinases (A, B, and M) in the serum, thereby promoting a hypertensive set of reactions. We report here the results of a study on the effect of acetaldehyde upon cathepsin G and mast cell chymase. Acetaldehyde enhanced cathepsin G activity at all of the concentrations tested between 11.2 and 223.5 mM in a statistically significant manner. Since cathepsin G is one of several enzymes transforming ANG I into ANG II and is also capable of cleaving ANG II directly from angiotensinogen, we suggest that alcoholism, which will generate exogenous acetaldehyde from ingested alcohol, may be a contributory factor for an elevated cathepsin G activity and, consequently, hypertension via the NRAS. Chymase activity also is elevated in the presence of 440 mM acetaldehyde and diminished in the presence of 27 mM acetaldehyde. Since both enzymes also degrade ANG II, the degradative effects of each enzyme on ANG II may neutralize one another.     

肥大细胞在大鼠胰腺组织纤维化形成中的作用及其机制

目的探讨肥大细胞（MC）在大鼠胰腺组织纤维化形成中的作用和机制。方法建立经逆行胆胰管注射2％三硝基苯磺酸（TNBS）诱导大鼠慢性胰腺炎模型，将大鼠分为三组，每组40只，分别用肥大细胞膜稳定剂色甘酸钠和MC激动剂48／80化合物及生理盐水进行干预，并于第3、7、14、21和28天处死动物。H—E染色观察胰腺组织病理学改变；Van Gieson染色观察胰腺组织纤维化情况；硫堇蓝染色观察大鼠慢性胰腺炎过程中MC分布、形态和数量的改变；免疫组化染色观察大鼠慢性胰腺炎α-平滑肌肌动蛋白（α-SMA）、转化生长因子（TGF）β1的表达；逆转录-多聚酶链反应（RT—PCR）观察血管紧张素Ⅱ1型（AT1）和2型（AT2）受体蛋白的表达。结果2％TNBS胰管内注射后可于第4周引起典型大鼠胰腺组织纤维化，在胰腺纤维化区域可见大量Ⅰ型胶原沉积。在此过程中MC存在着活化及脱颗粒。胰腺组织α—SMA、TGFβ1、AT1和AT2 mRNA蛋白制模早期表达即为阳性，至第4周时最强。与对照（生理盐水）组比较，色甘酸钠组MC数量及脱颗粒现象明显减少，α-SMA、TGFβ1蛋白表达和AT1、AT2受体mRNA表达明显减少；48／80化合物组MC数量及脱颗粒现象明显增多，上述各指标的表达均有不同程度的增加。结论MC参与TNBS诱导的大鼠慢性胰腺炎的炎症和纤维化的发生及发展，其机制可能与MC促进胰腺星状细胞活化，上调血管紧张素Ⅱ受体表达等介导了胰腺纤维化的形成。     

Is there a role for balloon valvuloplasty in patients with stenotic aortic bioprosthetic valves?

The management of patients with stenotic aortic bioprostheses is usually surgical. However, a proportion of such patients are unfit for such procedures. The technique of aortic balloon valvuloplasty as an alternative treatment strategy for such patients is explored.     

Cells of primarily extra-valvular origin in degenerative aortic valves and bioprostheses.

AIMS: We assessed aortic valves from patients with non-rheumatic aortic valve stenosis (AS) and with degenerative aortic valve bioprostheses (BP) for the presence of progenitor cell and leukocyte subtype-specific markers. METHODS AND RESULTS: Diseased valve probes from a total of 87 patients (60 AS and 27 BP) were studied. We assessed presence and localization of endothelial progenitor cells (EPCs: CD34, CD133), dendritic cells (DCs: S100), T-lymphocytes (CD3), and macrophages (CD68) by immunohistochemical and morphometric analyses. In the majority of valves, we detected cell-bound signals of CD34 (48% of AS, 74% of BP, respectively), CD133 (58%/81%), S100 (58%/93%), CD3 (62%/81%), and CD68 (78%/93%). Labelled cells were predominantly localized within the valvular fibrosa. As key results, frequency of EPCs, DCs, macrophages, and lymphocytes was found significantly higher in BP when compared with AS (CD34: 19.2+/-23.2 vs. 5.7+/-13.0%; CD133: 13.7+/-12.4 vs. 5.5+/-8.3%; S100: 15.2+/-12.2 vs. 5.7+/-8.9%; CD3: 3.3+/-2.7 vs. 1.1+/-1.4%; CD68: 35.3+/-26.6 vs. 3.4+/-4.1%; each P相似文献   

The novel role of mast cells in the microenvironment of acute myocardial infarction

Mast cells are multifunctional cells containing various mediators, such as cytokines, tryptase, and histamine, and they have been identified in infarct myocardium. Here, we elucidated the roles of mast cells in a myocardial infarction (MI) rat model. We studied the physiological and functional roles of mast cell granules (MCGs), isolated from rat peritoneal fluid, on endothelial cells, neonatal cardiomyocytes, and infarct heart (1-hour occlusion of left coronary artery followed by reperfusion). The number of mast cells had two peak time points of appearance in the infarct region at 1 day and 21 days after MI induction in rats (p < 0.05 in each compared with sham-operated heart). Simultaneous injection of an optimal dose of MCGs modulated the microenvironment and resulted in the increased infiltration of macrophages and decreased apoptosis of cardiomyocytes without change in the mast cell number in infarct myocardium. Moreover, MCG injection attenuated the progression of MI through angiogenesis and preserved left ventricular function after MI. MCG-treated cardiomyocytes were more resistant to hypoxic injury through phosphorylation of Akt, and MCG-treated endothelial cells showed enhanced migration and tube formation. We have shown that MCGs have novel cardioprotective roles in MI via the prolonged survival of cardiomyocytes and the induction of angiogenesis.     

In vitro measurement of stenotic human aortic valve orifice area in a pulsatile flow model. Validation of the continuity equation

Aortic valve orifice area estimation in patients with aortic stenosis may be obtained non-invasively using several Doppler echocardiographic methods. Their validity has been established by correlation with catheterization data using the Gorlin formula, with its inherent limitations, and small discrepancies between the methods are present. To evaluate these differences further, 15 patients with severe aortic stenosis (mean transvalvular gradient 70, range 40-130 mmHg) had aortic valve area estimations by Doppler echocardiography using two variations of the continuity equation. The intact valves removed at valve replacement surgery were then mounted in a pulsatile model and the anatomical area was measured (mean 0.67 +/- 0.17 cm-2) from video recordings during flow at 5.4 l min-1. Aortic valve area calculated using the integrals of the velocity-time curves measured at the left ventricular outflow tract and aortic jet (mean 0.65 +/- 0.17 cm2) correlated best with the anatomical area (r = 0.87, P less than 0.001). The area derived by using the ratio of maximum velocities from the left ventricular outflow tract and aortic jet (mean 0.69 +/- 0.18 cm2) also correlated well with the anatomical area (r = 0.79, P less than 0.001). The index between the left ventricular outflow tract and aortic jet maximum velocities was less than or equal to 0.25 in all. In patients with severe aortic stenosis the aortic valve area can be reliably estimated using Doppler echocardiography.     

钙化性主动脉瓣狭窄的外科治疗

目的评价钙化性主动脉瓣狭窄外科治疗效果及成功因素。方法对26例钙化性主动脉瓣狭窄患者随访分析,年龄55～70岁,平均62岁。主动脉跨瓣压差52～191mmHg,平均97mmHg,室间隔、左室后壁厚度14～19mm,合并关闭不全7例。手术均在全麻、低温和体外循环下行机械瓣置换,同期行Manouguian法扩大主动脉瓣环9例、CABG3例、Wheat术1例。结果术后早期和晚期各死亡1例。随访心脏超声LVEF为51%～72%,室间隔及左室后壁厚度8～12mm,人工瓣跨瓣压差8～26mmHg。心功能为Ⅰ～Ⅱ级。结论瓣膜置换是治疗钙化性主动脉瓣狭窄唯一安全有效的方法,恰当的手术时机、合适的瓣膜型号是提高手术远期疗效的重要保证。     

Validation of methods for effective orifice area measurement of prosthetic valves by two-dimensional and Doppler echocardiography following transcatheter self-expanding aortic valve implantation

BackgroundThe effective orifice area (EOA) is utilized to characterize the hemodynamic performance of the transcatheter heart valve (THV). However, there is no consensus on EOA measurement of self-expanding THV. We aimed to compare two echocardiographic methods for EOA measurement following transcatheter self-expanding aortic valve implantation.MethodsEOA was calculated according to the continuity equation. Two methods were constructed. In Method 1 and Method 2, the left ventricular outflow tract diameter (LVOTd) was measured at the entry of the prosthesis (from trailing-to-leading edge) and proximal to the prosthetic valve leaflets (from trailing-to- leading edge), respectively. The velocity-time integral (VTI) of the LVOT (VTI_LVOT) was recorded by pulsed-wave Doppler (PW) from apical windows. The region of the PW sampling should match that of the LVOTd measurement with precise localization. The mean transvalvular pressure gradient (MG) and VTI of THV was measured by Continuous wave Doppler.ResultsA total of 113 consecutive patients were recruited. The mean age was 77.2 ± 5.5 years, and 72 patients (63.7%) were male. EOA₁ with the use of Method 1 was larger than EOA₂ (1.56 ± 0.39 cm² vs. 1.48 ± 0.41 cm², P = 0.001). MG correlated better with the indexed EOA₁ (EOAI₁) (r = -0.701, P < 0.001) than EOAI₂ (r = -0.645, P < 0.001). According to EOAI (EOAI ≤ 0.65 cm²/m², respectively), the proportion of sever prosthesis-patient mismatch with the use of EOA₁ was lower than EOA₂ (12.4% vs. 21.2%, P < 0.05). Compared with EOA₂, EOA₁ had lower interobserver and intra-observer variability (intra: 0.5% ± 17% vs. 3.8% ± 22%, P < 0.001; inter: 1.0% ± 9% vs. 3.5% ± 11%, P < 0.001).ConclusionsFor transcatheter self-expanding valve EOA measurement, LVOTd should be measured in the entry of the prosthesis stent (from trailing-to-leading edge), and VTI_LVOT should match that of the LVOTd measurement with precise localization.     

Special considerations on TAVI implanted in bicuspid aortic valves: Experience of Institute of Cardiology in Warsaw,Poland

Since the advent of transcatheter aortic valve implantation (TAVI), bicuspid aortic valves (BAVs) have been considered relative contraindication for this procedure. Patients with BAV were excluded from the majority of large clinical TAVI trials. However, the development of the implantation technique and further studies have proven this method feasible and safe also in BAVs. Nowadays some clinicians claim that BAV should no longer be a contraindication. Nevertheless some special aspects of the unique anatomy need to be taken into consideration when qualifying patients for this procedure.In our center since 2010 a total number of 28 patients with bicuspid aortic valve stenosis underwent TAVI.     

Congenital valvular aortic stenosis in young adults: Predictors for rate of progression of stenosis and aortic dilatation

Background

Congenital aortic stenosis (AS) is the most common obstructive left-sided cardiac lesion in young adults, however little is known about the progression in adults. Therefore, we aimed to evaluate the progression rate of AS and aortic dilatation in a large multicenter retrospective cohort of asymptomatic young adults with congenital valvular AS.

Methods

Data were obtained from chart abstraction. Linear mixed-effects models were used to evaluate the progression of AS and aortic dilatation over time. A joint model combining longitudinal echocardiographic and survival data was used for survival analysis.

Results

A total of 414 patients (age 29 ± 10 years, 68% male) were included. Median follow-up duration was 4.1 (2.5–5.1) years (1587 patient-years). Peak aortic velocity was 3.4 ± 0.7 m/s at baseline and did not change over time in the total patient population (− 0.01 ± 0.03 m/s/year). Increased left ventricular mass was significantly associated with faster AS progression (p < 0.001). Aortic dilatation was present in 34% at baseline and 48% at follow-up (p < 0.001). The aortic diameter linearly increased over time with a rate of 0.7 ± 0.2 mm/year. Rate of aortic dissection was 0.06% per patient-year. Seventy patients required an aortic valve intervention (4.4% per patient-year), with AS progression rate as most powerful predictor (HR 5.11 (95% CI 3.47–7.53)).

Conclusions

In the majority of patients with mild-to-moderate congenital AS, AS severity does not progress over time. However patients with left ventricular hypertrophy are at risk for faster progression and should be monitored carefully. Although aortic dissections rarely occur, aortic dilatation is common and steadily progresses over time, warranting serial aortic imaging.     

Noninvasive quantification of the aortic valve area in aortic stenosis by Doppler echocardiography

To develop a noninvasive approach to the quantification of thestenotic aortic valve area, Doppler echocardiography and cardiaccatheterisation were performed in 24 patients with pure aorticstenosis. The transmitral volumetric flow was measured by Dopplerechocardiography and calculated as the product of the correctedmitral orifice area (CM A) and the diastolic velocity integral(DVI). The maximal aortic jet velocities were recorded by Dopplertechnique and integrated to obtain the systolic velocity integral(SVl). Assuming that the aortic and mitral volumetric flowsare equal, the aortic valve area (A VA) was calculated as: AVA= CM A x DVI/SVI. Mean pressure gradient and cardiac outputwere measured during catheterisation and the aortic valve areawas calculated by the Gorlin formula. Comparison between theaortic valve area determined by Doppler technique and catheterisationyielded a close correlation (r = 0.92, P<0.001), and therewas no significant difference between the two measurements.Good correlations of the instantaneous pressure gradient andthe stroke volume were also obtained between the two techniques(r = 0.91 and r = 0.90, respectively, P<0.001). These resultsdemonstrate that our Doppler echocardiographic method providesa promising approach to the noninvasive quantification of theaortic valve area in aortic stenosis     

Clinical outcome and quality of life in octogenarians following transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis

Objective

TAVI is the alternative option in pts with AS deemed ineligible for surgery. Although mortality and morbidity are measures to assess the effectiveness of treatments, quality of life (QOL) should be an additional target. We assessed clinical outcome and QOL in octogenarians following TAVI.

Design

All octogenarians with a risk profile considered by the Heart Team to be unacceptable for surgery entered in this registry. QOL was assessed by questionnaires concerning physical and psychic performance.

Patients

A hundred forty-five octogenarians (age: 84.7 ± 3.4 years; male: 48.3%) underwent TAVI for AS (97.2%) or isolated AR (2.8%). NYHA class: 2.8 ± 0.6; Logistic EuroScore: 26.1 ± 16.7; STS score: 9.2 ± 7.7.Echocardiographic assessments included AVA (0.77 ± 0.21 cm2), mean/peak gradients (54.5 ± 12.2/88 ± 19.5 mmHg), LVEF (21% = EF ≤ 40%), sPAP (43.1 ± 11.6 mmHg).

Interventions

All pts underwent successful TAVI using Edward-SAPIEN valve (71.2%) or Medtronic CoreValve (28.8%).

Main outcome measures

Rates of mortality at 30 days, 6 months and 1 year were 2.8%, 11.2% and 17.5%.

Results

At 16-month follow up, 85.5% survived showing improved NYHA class (2.8 ± 0.6 vs 1.5 ± 0.7; p < 0.001), decreased sPAP (43.1 ± 11.6 mmHg vs 37.1 ± 7.7 mmHg; p < 0.001) and increased LVEF in those with EF ≤ 40% (34.9 ± 6% vs 43.5 ± 14.4%; p = 0.006). Concerning QOL, 49% walked unassisted, 79% (39.5% among pts ≥ 85 years) reported self-awareness improvement; QOL was reported as “good” in 58% (31.4% among pts ≥ 85 years), “acceptable according to age” in 34% (16% among pts ≥ 85 years) and “bad” in 8%.

Conclusion

TAVI procedures improve clinical outcome and subjective health-related QOL in very elderly patients with symptomatic AS.     

Early valve replacement for aortic stenosis irrespective of symptoms results in better clinical survival: A meta-analysis of the current evidence

Objectives

Patients with severe, but asymptomatic aortic stenosis (AS) present a difficult clinical challenge. The conventional strategy is ‘wait for symptoms’ approach. However, some observational studies have suggested early aortic valve replacement (AVR) results in better outcome compared to late surgery. There are no randomised controlled trials comparing clinical outcome of early and late AVR. This meta-analysis is to examine the effect of the two approaches on clinical outcome in such patients.

Methods

We searched the PubMed for published studies on asymptomatic AS and treatment. Four observational studies (N = 976 patients) were suitable for inclusion in the analysis.

Results

All four studies provided sufficient details. Using the subgroup of asymptomatic patients who underwent early surgery together or separately from the subgroup who had surgery after developing symptoms resulted in ORs of 0.17 and 0.16 respectively (p < 0.00001) in favour of early AVR compared with conservational or late surgery.

Conclusion

Meta-analysis of the available observational studies has demonstrated highly significant clinical outcome in favour of early AVR compared with late surgery, suggesting that early surgical approach offers substantial survival benefit for severe asymptomatic AS patients.     

结肠黏膜肥大细胞活化在肠易激综合征发病中的作用

目的　探讨结肠黏膜肥大细胞活化在肠易激综合征 (IBS)发病机制中的作用。方法　采用c Fos和类胰蛋白酶免疫组化双标方法 ,对应激和条件应激肠功能紊乱大鼠及符合罗马Ⅱ标准、连续就诊的发作期IBS患者 5 6例进行直肠乙状结肠交界处黏膜肥大细胞活化程度研究 ,并与对照大鼠和健康对照组及 2例无症状超过 6个月的IBS患者相比较 ,观察应激和条件应激大鼠在应激前 30min腹腔注射 (i.p .)肥大细胞稳定剂色甘酸二钠 2 0mg/kg对大鼠内脏敏感性的影响 ,通过Spearman等级相关分析评价IBS患者症状严重指数与肥大细胞活化分数的关系。结果　与对照组相比 ,应激 [(8.0± 0 .9)比(2 .5± 0 .8) ]和条件应激 [(7.8± 0 .8)比 (2 .5± 0 .8) ]大鼠结肠下段黏膜活化细胞明显增加 ,但肥大细胞总数无明显改变 ;色甘酸二钠显著降低应激大鼠 [(7.2± 1.2 )比 (3.8± 0 .8) ,P <0 .0 1]和条件应激大鼠[(6 .8± 0 .8)比 (3.8± 0 .8) ,P <0 .0 1]的内脏敏感性 ,对对照组大鼠却无影响。与 2 0例正常对照组相比 ,IBS发作期患者直肠乙状结肠交界处黏膜肥大细胞数目和活化细胞分数显著增加 [(85± 12 )比 (15± 6 ) ,P <0 .0 1],肥大细胞活化分数与症状严重程度指数显著相关 (r =0 .86 2 ,P <0 .0 1)。结论　肠道黏膜肥大细胞活化