Regional cardiac expression and concentration of natriuretic peptides in patients with severe chronic heart failure.

The purpose of this study was to examine the regional cardiac mRNA expression and concentration of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in relation to the circulating peptide concentrations in patients with chronic heart failure (CHF). The myocardial mRNA levels and peptide concentrations of BNP and ANP were analysed in seven different regions of the heart from patients undergoing cardiac transplantation. Autopsy samples from individuals without known cardiovascular disease were used as controls. The plasma levels of natriuretic peptides and their N-terminal propeptides, Nt-proBNP and Nt-proANP, were measured in the CHF patients and healthy volunteers. In the autopsy specimens, the atrial regions appeared to contain the highest peptide levels for BNP as well as ANP, the atrioventricular ratio being 12-262 and 72-637-fold, respectively. In the CHF patients there was a relative shift towards the ventricle for BNP, reducing the atrioventricular ratio to 6-16-fold. The circulating concentrations of BNP/Nt-proBNP in the CHF patients correlated closely to the BNP mRNA expression in most myocardial regions including the left ventricle (r = 0.72, P < 0.001). For circulating concentrations of ANP/Nt-proANP, such correlation were limited to the left atrium free wall (r = .66, P < 0.002). Thus, of the two natriuretic peptides, BNP/Nt-proBNP may be a better reflector of left ventricular overload.     

Cardiac natriuretic peptide hormones during artificial cardiac pacemaker stimulation and left heart catheterization

Summary Brain natriuretic peptide (BNP) is synthesized and released predominantly in the ventricular myocardium whereas atrial natriuretic peptide (ANP) is produced mainly in the atria. This study evaluated whether artificial pacemaker stimulation or left heart catheterization results in specific changes in BNP and ANP plasma levels. Both BNP and ANP responded sensitively to changes in pacemaker stimulation (single-chamber pacemakers; pacing rates of 72 and 92/min) and during the left heart catheterization procedure. However, whereas higher pacing resulted in a more pronounced increase in plasma BNP levels, a stronger ANP release followed catheterization. This incongruous rise in ANP and BNP plasma concentrations points to at least partly independent mechanisms govering the release of BNP and ANP.Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide     

Regional cardiac expression and concentration of natriuretic peptides in patients with severe chronic heart failure

The purpose of this study was to examine the regional cardiac mRNA expression and concentration of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in relation to the circulating peptide concentrations in patients with chronic heart failure (CHF). The myocardial mRNA levels and peptide concentrations of BNP and ANP were analysed in seven different regions of the heart from patients undergoing cardiac transplantation. Autopsy samples from individuals without known cardiovascular disease were used as controls. The plasma levels of natriuretic peptides and their N‐terminal propeptides, Nt‐proBNP and Nt‐proANP, were measured in the CHF patients and healthy volunteers. In the autopsy specimens, the atrial regions appeared to contain the highest peptide levels for BNP as well as ANP, the atrioventricular ratio being 12–262 and 72–637‐fold, respectively. In the CHF patients there was a relative shift towards the ventricle for BNP, reducing the atrioventricular ratio to 6–16‐fold. The circulating concentrations of BNP/Nt‐proBNP in the CHF patients correlated closely to the BNP mRNA expression in most myocardial regions including the left ventricle (r=0.72, P < 0.001). For circulating concentrations of ANP/Nt‐proANP, such correlation were limited to the left atrium free wall (r=0.66, P < 0.002). Thus, of the two natriuretic peptides, BNP/Nt‐proBNP may be a better reflector of left ventricular overload.     

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.     

Mechanisms of mechanical load-induced atrial natriuretic peptide secretion: role of endothelin, nitric oxide, and angiotensin II

There are three members in the natriuretic peptide hormone family, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP, brain natriuretic peptide), and C-type natriuretic peptide (CNP), that are involved in the regulation of blood pressure and fluid homeostasis. CNP is found principally in the central nervous system and vascular endothelial cells while ANP and BNP are cardiac hormones. ANP is synthesized mainly in the atria of the normal adult heart, while BNP is produced by both the atria and ventricles. The mechanisms controlling ANP release have been the subject of intense research, and are now fairly well understood. The major determinant of ANP secretion is myocyte stretch. Although much less is known about the factors regulating BNP release from the heart, myocyte stretch has also been reported to stimulate BNP release from both atria and ventricles. However, whether wall stretch acts directly or via factors such as endothelin-1, nitric oxide, or angiotensin II liberated in response to distension has not been established. Recent studies show that by stimulating endothelin type A receptors endothelin plays an important physiological role as a mediator of acute-volume load-induced ANP secretion from atrial myocytes in conscious animals. In fact, endogenous paracrine/autocrine factors liberated in response to atrial wall stretch rather than direct stretch appears to be responsible for activation of ANP secretion in response to volume load, as evidenced by almost complete blockade of ANP secretion during combined inhibition of endothelin type A/B and angiotensin II receptors. Furthermore, under certain experimental conditions angiotensin II and nitric oxide may also exert a significant modulatory effect on stretch-activated ANP secretion. The molecular mechanisms by which endothelin-1, angiotensin II, and nitric oxide synergistically regulate stretch-activated ANP release are yet unclear.     

Increased cardiac weight in interleukin-6 transgenic mice with viral infection accompanies impaired expression of natriuretic peptide genes

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) regulate cardiac hypertrophy. We investigated ventricular alterations of ANP and BNP in interleukin-6 (IL-6) transgenic mice (TG) and wild type (WT) mice with or without viral infection. The ANP and BNP mRNA/GAPDH mRNA ratios in the ventricles of IL-6 TG mice were twice that of WT mice, but were not increased significantly by viral inoculation. In WT mice, both ANP and BNP responses were significantly increased in the ventricles of mice 10 days after encephalomyocarditis (EMC) viral inoculation. Cardiac weight in IL-6 TG mice was significantly greater than in WT 10 days after viral inoculation. Left ventricular wall thickness and the diameter of ventricular myocytes also were greater in IL-6 TG than WT after viral infection. Primary cultures of neonatal rat cardiac myocyte showed that IL-6 increased ANP and BNP mRNA expression in a dose-responsive fashion. In summary, overexpression of ANP and BNP occurs in the ventricles of IL-6 TG mice, along with increased cardiac weight after infection with EMC virus, and impaired responses in the expression of ANP and BNP.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug     

一肾一夹和两肾一夹高血压和血压逆转大鼠血浆、心房和心室心钠素水平的变化特征

利用一肾一夹容量型和两肾一夹压力型大鼠肾血管性高血压所敛心肌肥厚及高血压逆转肥厚逆转模型,测定血浆、心房和心审心钠素水平。发现两型高血压大鼠血浆及左室的心钠素水平明显增高,左室及血浆心钠素浓度与相对室重呈正相关,左房心钠素浓度在一肾一夹型明显降低;随着高血压的逆转,两型大鼠血浆及心房心钠素水平基本恢复,增高了的心室心钠素由高水平下降。结果提示。在高血压、容量扩张并伴有心肌肥厚的病理情况下,心室心钠素可能起重要的代偿调节作用。     

Cardiac rhabdomyoma. A case report with reference to atrial natriuretic peptide

An autopsy case of cardiac rhabdomyoma in a male infant is reported. Many nodules of rhabdomyoma were present in all four cardiac chambers and were microscopically composed of ovoid, glycogen-laden cells and typical "spider cells". Atrial natriuretic peptide (ANP) was immunohistochemically demonstrated in both normal myocytes and rhabdomyoma cells of both atria, but not in normal myocytes and rhabdomyoma cells of both ventricles. Ultrastructurally, atrial specific granules were present in atrial rhabdomyoma cells and normal atrial cardiocytes, and these showed ANP immunoreactivity with protein A-gold technique. It could be said that the localization and intracellular distribution of ANP in this cardiac rhabdomyoma were closely similar to those of normal human heart. With regard to the presence of ANP, cardiac rhabdomyoma cells arising in atria seemed to differ from those in ventricles, although many tumor nodules occurred in both atria and ventricles. Furthermore, it seemed that cardiac rhabdomyomas could also be divided into two parts: 1) an atrial part with ANP, and 2) a ventricular part without ANP. Therefore, this study confirms the hypothesis that cardiac rhabdomyoma is a hamartoma rather than a true neoplasm.     

Cardiac natriuretic peptides and continuously monitored atrial pressures during chronic rapid pacing in pigs

Changes in atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide and brain natriuretic peptide (BNP) were evaluated in relation to continuously monitored atrial pressures in a pacing model of heart failure. Pigs were subjected to rapid atrial pacing (225 beats min-1) for 3 weeks with adjustments of pacing frequencies if the pigs showed overt signs of cardiac decompensation. Atrial pressures were monitored by a telemetry system with the animals unsedated and freely moving. Left atrial pressure responded stronger and more rapidly to the initiation of pacing and to alterations in the rate of pacing than right atrial pressure. Plasma natriuretic peptide levels were measured by radioimmunoassay and all increased during pacing with BNP exhibiting the largest relative increase (2.9-fold increase relative to sham pigs). Multiple regression analysis with dummy variables was used to evaluate the relative changes in natriuretic peptides and atrial pressures and the strongest correlation was found between BNP and left atrial pressure with R 2=0.81. Termination of pacing resulted in rapid normalization of ANP values in spite of persistent elevations in atrial pressures. This may reflect an increased metabolism or an attenuated secretory response of ANP to atrial stretch with established heart failure. In conclusion, 3 weeks of rapid pacing induced significant increases in atrial pressures and natriuretic peptide levels. All the natriuretic peptides correlated with atrial pressures with BNP appearing as a more sensitive marker of cardiac filling pressures than ANP and N-terminal proatrial natriuretic peptide.     

Role of calcium in stretch-induced release and mRNA synthesis of natriuretic peptides in isolated rat atrium

 To investigate the role of Ca²⁺ in stretch-induced synthesis and release of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) isolated superfused rat atria were stretched by raising intra-atrial pressure. The immunoreactive (ir-) ANP and BNP concentrations were analysed by radioimmunoassay and the corresponding mRNA levels were quantified by Northern blot and dot blot analyses. Stretch-induced ir-ANP release and a rise in BNP mRNA levels increased at high (3.0 mM) compared to low (0.5 mM) extracellular Ca²⁺ concentration ([Ca²⁺]_o). Moreover, the adaptation of stretch-induced ir-ANP release was dependent on [Ca²⁺]_o. Atrial BNP mRNA levels were increased by stretch also in non-paced, electrically silent atria, where voltage-activated Ca²⁺ channels are not activated. The stretch-induced rise in BNP mRNA was blocked by gadolinium (80 μM), but not by the L-type channel blocker diltiazem (3.0 μM). This study indicates that both the stretch-secretion coupling of ir-ANP release and the pressure-stimulated synthesis of BNP mRNA are Ca²⁺-dependent processes. Gadolinium inhibits the stretch-stimulated rise in BNP mRNA levels in contracting and non-contracting atria, which is similar to its ability to block stretch-activated ir-ANP release, suggesting the involvement of Ca²⁺-permeable stretch-activated channels. Received: 29 April 1996 / Received after revision and accepted: 17 June 1996     

CARDIAC RHABDOMYOMA: A Case Report with Reference to Atrial Natriuretic Peptide

An autopsy case of cardiac rhabdomyoma in a male infant is reported. Many nodules of rhabdomyoma were present in all four cardiac chambers and were microscopically composed of ovoid, glycogen-laden cells and typical "spider cells". Atrial natriuretic peptide (ANP) was immunohistochemically demonstrated in both normal myocytes and rhabdomyoma cells of both atria, but not in normal myocytes and rhabdomyoma cells of both ventricles. Ultrastructurally, atrial specific granules were present in atrial rhabdomyoma cells and normal atrial cardiocytes, and these showed ANP immunoreactivity with protein A-gold technique. It could be said that the localization and intracel-Mar distribution of ANP in this cardiac rhabdomyoma were closely similar to those of normal human heart. With regard to the presence of ANP, cardiac rhabdomyoma cells arising in atria seemed to differ from those in ventricles, although many tumor nodules occurred in both atria and ventricles. Furthermore, it seemed that cardiac rhabdomyomas could also be divided into two parts: 1) an atrial part with ANP, and 2) a ventricular part without ANP. Therefore, this study confirms the hypothesis that cardiac rhabdomyoma is a hamartoma rather than a true neoplasm. ACTA PATHOL JPN 38 : 95–104, 1988.     

Brain natriuretic peptide

Plasma levels of various neurohumoral factors are activated and have an important role of the pathophysiology of congestive heart failure (CHF). Atrial natriuretic peptide (ANP) and brain (or B-type) natriuretic peptide (BNP) are secreted from cardiomyocytes in response to atrial or ventricular wall stretch. The natriuretic peptides have a fundamental role in cardiovascular remodeling, volume homeostasis, and the response to myocardial injury. Clinical investigations of these peptides have focused on their diagnostic usefulness for heart failure and left ventricular dysfunction and their prognostic usefulness after acute coronary syndromes and heart failure. In patients with left ventricular systolic dysfunction, a high plasma BNP level is an independent prognostic predictor of CHF patients, suggesting that the compensatory activity of the cardiac natriuretic peptide system is attenuated as mortality increases in chronic CHF patients with high plasma levels of ANP and BNP. BNP is more useful than ANP for diagnosis and management of CHF. Recently, rapid BNP assay is available in our country, rapid measurement of BNP in the emergency department may improve the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment. In addition, BNP-guided treatment of heart failure may reduce total cardiovascular events, and delayed time to first event combination with intensive clinically guided treatment.     

Exercise-induced physiological hypertrophy initiates activation of cardiac progenitor cells

Objective: Physiological hypertrophy is featured by the hypertrophy of pre-existing cardiomyocytes and the formation of new cardiomyocytes. C-kit positive cardiac progenitor cells increased their numbers in exercise-induced physiological hypertrophy. However, the participation of Sca-1 positive cells in the physiological adaptation of the heart to exercise training is unclear. Methods: Physiological hypertrophy was induced by swimming and the mRNA levels of GATA binding protein 4 (GATA4), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endogenous hepatocyte growth factor (HGF), and insulin like growth factor-1 (IGF-1) from the whole heart were determined by real-time polymerase chain reactions (RT-PCRs) analysis. Immunofluorescent staining was used to compare the number of C-kit and Sca-1 positive cardiac progenitor cells. In addition, mRNA levels of C-kit and Sca-1 in left ventricle (LV), right ventricle (RV), and outflow tract (OFT) were determined in mice swimming for 7, 14, and 21 days by RT-PCRs. Results: The ratio of heart weight (HW) to body weight and HW to tibia length and the mRNA level of GATA4 were increased while mRNA levels of ANP and BNP remained unchanged. C-kit and Sca-1 positive cardiac progenitor cells were activated by swimming training. An increased endogenous production of HGF and IGF was observed at least at the mRNA level. Swimming induced a significant up-regulation of C-kit in LV of mice swimming for 1, 2 and 3 weeks and in RV of mice swimming for 3 weeks. Sca-1 positive cardiac progenitor cells were increased in LV and OFT in mice swimming for 3 weeks. Conclusion: This study presents that swimming-induced physiological hypertrophy initiates activation of cardiac progenitor cells.     

Atrial natriuretic peptide and its mRNA in heart and brain of vasopressin-deficient Brattleboro rats

To understand the secretion and synthesis of atrial natriuretic peptide we measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and brain areas, and ANP mRNA was determined from heart auricles and ventricles of vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI + DDAVP). Long-Evans rats (LE) served as controls. DI + DDAVP rats were given for 3 days sc. injections of 0.5/g l-desamino-8-D-arginine vasopressin in 1 ml. saline twice a day. The rats were housed in single metabolic cages and urinary output and water intake were measured daily. All the body and organ weight parameters were similar in the three groups when the rats were killed. No change was seen in the plasma ANP level between the groups. The right ventricle of DI + DDAVP rats had significantly (P < 0.05) higher concentration of ANP than LE rats (15.8 + 4.4 vs. 3.4 + 0.6 ng mg“¹ tissue). The left ventricle of DI and DI+DDAVP had significantly (P < 0.05) lower amounts of ANP mRNA than LE rats (0.5 ± 0.2 vs. 1.3 + 0.2 and 0.5 + 0.1 vs. 1.3 + 0.2 arbitrary units). In the hypothalamus, the ANP concentration was significantly (P < 0.05) lower both in DI and in DI + DDAVP rats than in LE rats (9.3 ±1.3 vs. 14.5 ±±1.6 and 6.1+0.6 vs. 14.5 ± 1.6 pg mg^-1 tissue). To conclude, although the water intake and urinary output of DI rats were changed towards normal with desmopressin treatment, the heart ventricular and hypothalamic ANP did not parallel the change. Desmopressin increased the ANP concentration in the right ventricle of DI rats. Thus the correction of the complete vasopressin deficiency-does not appear to associate with synthesis or release of atrial natriuretic peptide in heart or hypothalamus.     

C-type natriuretic peptide does not affect plasma and urinary adrenomedullin in man.

To investigate whether C-type natriuretic peptide (CNP) at pathophysiological plasma levels stimulates the release of adrenomedullin (ADM) in man, six healthy subjects (three men and three women, mean age 35 +/- 3 years, range 33-40 years) received an intravenous infusion of synthetic human CNP-22 (2 pmol kg-1 min for 2 h), in a single-blind, placebo-controlled, random order, cross-over study, with measurements of the plasma levels of cyclic guanosine monophosphate (cGMP), ADM, renin and atrial natriuretic peptide (ANP), arterial pressure, heart rate, renal blood flow (para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), and the urinary excretion rates of cGMP, ADM and sodium. Infusion of CNP induced increases in its own levels (from 1.17 +/- 0.11 up to 21.13 +/- 1.41 pmol l-1) without modifying the plasma levels of cGMP, ADM, renin and ANP, the urinary excretion rate of ADM and cGMP, renal haemodynamics and sodium excretion. These data indicate that circulating CNP is not involved in the regulation of ADM release, renal haemodynamics and sodium excretion in man.     

Case report of a heart transplantation in a 16-year-old male

We examined ultrastructural changes and did immunohistochemical studies of atrial natriuretic peptide (ANP) in biopsied samples obtained from the heart of a 16-year-old Japanese boy with dilated cardiomyopathy and from the transplanted donor heart. In the right ventricle of the diseased heart, a small number of atrial granules containing ANP were found in the perinuclear area of the cardiomyocytes and near areas lacking some myofibrils. Although no evidence of rejection was seen in the right ventricle of the transplanted donor heart under the light microscope, electron microscopy revealed moderate degeneration of cardiomyocytes and injuries to capillary endothelial cells. We did not find atrial granules, although the serum ANP level was elevated. These data suggest that the ultrastructural changes in the transplanted heart were related to a mild rejection, the effects of cyclosporin, or the effects of a domino heart transplantation from a patient with cystic fibrosis. Because of the absence of atrial granules in the right venticle, it is postulated that the high serum ANP level may be attributed to merely an increased secretion of ANP from atrial granules in the atria, without secretion of ANP in the ventricles.     

静脉注射IL-19重组质粒对大鼠实验性自身免疫性心肌炎的治疗作用

目的:评估静脉注射白细胞介素19(interleukin-19,IL-19)重组质粒对大鼠实验性自身免疫性心肌炎(experimental autoimmune myocarditis,EAM)的治疗作用。方法:将猪心室肌球蛋白与等体积完全弗氏免疫佐剂充分混匀后,双足皮下注射制作大鼠EAM模型,免疫后第6天应用静脉注射方法将IL-19重组质粒导入体内,第17天行心脏超声检查后处死大鼠,检测心脏重量与体重比值、病理学评估、心肌炎面积率;实时荧光定量PCR检测心衰标记物心房钠尿肽(atrial natriuretic peptide,ANP)、脑钠尿肽(brain natriuretic peptide,BNP)的表达水平,进一步检测心肌相关炎症因子IL-18、IL-1β、IL-12p35和IFN-γ的表达水平。结果:IL-19重组质粒导入组的大鼠心功能得到显著改善;心脏重量体重比、心肌炎面积率、ANP、BNP的表达均较模型组明显下降;相关炎症细胞因子的表达也显著降低。结论:应用静脉注射法进行IL-19重组质粒体内导入治疗,明显抑制大鼠实验性自身免疫性心肌炎的炎症反应,减轻了心肌损伤从而改善心功能。