Correlations between adrenal weight and heart weight in rats with a cardiac overload

A significant positive correlation between heart weight and adrenal weight was found in rats with myocardial hypertrophy induced by experimental hyperthyroidism or ligation of the abdominal aorta. The simultaneous administration of digitoxin partly inhibited myocardial hypertrophy after ligation of the abdominal aorta, but not after experimental hyperthyroidism. Digitoxin also inhibited adrenal hypertrophy after ligature of the abdominal aorta but, again, not after experimental hyperthyroidism. The possible existence of an endogenous cardiotropic hormone participating in the development of cardiac hypertrophy from overloading is discussed.     

Experimental cardiac hypertrophy induced by isoproterenol in the rat.

Isoproterenol (IPR) administered to rats in a dose of 5 mg/kg for seven days induces cardiomegaly. To determine the degree of myocardial enlargement, wet and dry heart weight, myocardial RNA, DNA, protein content and protein synthesis were measured. Wet and dry heart weight, and the level of cardiac RNA, DNA and protein were augmented by IPR treatment, with RNA increasing more than DNA and protein. Incorporation of 14C-leucine into the protein of the heart was enhanced by IPR. Thus the IPR-induced cardiomegaly may serve as a model for studying the development of cardiac hypertrophy under various conditions.     

Study of the factors influencing cardiac growth. I. Comparison of cardiomegaly induced by isoproterenol in euthyroid and thyroidectomized rats

The purpose of the present work was to study the cardiac growth-stimulating effect of IPR in hypothyroid animals, in which the in vitro sensitivity of the myocardium to beta-adrenergic agonists is significantly decreased. To determine the degree of myocardial enlargement, wet and dry ventricle weight and myocardial RNA, DNA and protein were measured. IPR administered to euthyroid rats in a dosage of 5 mg/kg/day for 4 days induced cardiomegaly. In thyroidectomized rats, a consistent depression of IPR-induced cardiomegaly was observed. This phenomenon appears to be in accordance with earlier observations showing a marked decrease in maximal beta-receptor level of ventricular membranes after thyroidectomy or PTU treatment.     

Ultrastructural and electrophysiological alterations during the development of catecholamine-induced cardiac hypertrophy and failure

Cardiac hypertrophy and failure were induced in male Wistar rats by daily administration of 5 mg/kg isoproterenol for three weeks. Age-matched animals were used as normal control. To estimate the degree of hypertrophy, the wet heart weight (HW) to body weight (BW) ratio (HW/BW) was used as an index of the myocardial enlargement. By the 7th day of the treatment, the HW/BW ratio was increased to 4.24, as compared with the control value of 3.11. In this early stage of cardiomyopathy, the structure was characterized with small necrotic foci, enlarged myofilaments and swollen mitochondria. The electrical activity showed broadened action potentials with an elevated plateau phase, and increased membrane resistance and time constant. The amplitude of the twitch contractions was elevated. Continuing the treatment of the animals with catecholamine caused a decompensated heart failure by the 21st day. In this late stage, many and large necrotic foci could be observed in the myocardium. The mitochondria were fragmented, and the resistance of the sarcolemma decreased, and the electrical and contractile activity suppressed. The results indicate that an electrically and structurally compensated cardiac hypertrophy model can be produced by a short-term treatment of the animals with isoproterenol, while a long-term treatment causes a decompensated heart failure.     

Early onset of the maximum protein anabolic effect induced by isoproterenol in chick skeletal and cardiac muscle

Prolonged (120 days) oral administration of a beta adrenoceptor agonist, isoproterenol hydrochloride (dose = 1.5 mg/kg body weight) resulted in an increase in the live weight of growing chicks (Callus domesticus). Measurement of dry muscle mass and total proteins in muscle homogenates from M. pectoralis major. M. petoralis minor suggested a muscle hypertrophy largely responsible for this live weight increase. Further, an increase in organ weight and total tissue proteins supported cardiac hypertrophy in chicks as a result of isoproterenol administration. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed alterations in actin myosin profiles implying a drug induced change in phenotypic expression of myofibrillar component of both skeletal and cardiac muscle. The results suggest that prolonged treatment of chicks produced changes that were not much different from those recorded immediately within a fortnight.     

Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling

The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.     

miRNA在异丙肾上腺素诱导大鼠心肌肥厚中的表达及生物信息学分析*

目的:探讨miRNAs(miR199a-5P、miR206、miR133a-3P、miR499-5P)在异丙肾上腺素(ISO)诱导大鼠心肌肥厚模型组中的表达变化;并运用生物信息学方法分析相关的主要信号通路及分子机制。方法:将16只SD雄性大鼠随机分为2组:对照组和ISO模型组,模型组给予ISO(1 mg/kg)诱导心肌肥厚模型,对照组给予等量生理盐水,均采用背部皮下多点注射。连续给药10 d后采用超声心动图测量舒张期室间隔厚度(IVSd)、舒张期左室后壁厚度(LVPWd)、左室舒张末期内径(LVDd)及心脏收缩功能(EF%);称量心脏重量(HW)、大鼠体重(BW),并计算心脏/体重比(HW/BW);心肌组织HE染色,Image J分析软件测量心肌细胞表面积;RT-qPCR检测大鼠心肌组织中4种miRNAs的表达情况。运用Targetscan、miRDB、miRwalk 数据库预测大鼠4种miRNAs可能的靶基因,FunRich软件分析预测靶基因相关的信号通路。结果:与正常组相比,模型组IVSd、LVPWd增厚,LV增大,EF%明显降低;HW、HW/BW增加;模型组心肌细胞体积明显增大,排列紊乱,细胞表面积增加;模型组miR199a-5P、miR206表达上调(P＜0.05);miR133a-3P、miR499-5P表达下调(P＜0.05)。应用生物信息学预测4种miRNAs的靶基因可能参与心肌肥厚相关的信号通路主要有:VEGF/VEGFR信号通路、ErbB受体信号通路等。结论:ISO诱导心肌肥厚导致miRNAs表达的改变,生物信息学预测4种miRNAs参与心肌肥厚相关的靶基因及其主要信号通路,这些研究为心肌肥厚的调控机制及其防治措施提供了新思路。     

Rac-Induced Left Ventricular Dilation in Thyroxin-Treated ZmRacD Transgenic Mice: Role of Cardiomyocyte Apoptosis and Myocardial Fibrosis

The pathways inducing the critical transition from compensated hypertrophy to cardiac dilation and failure remain poorly understood. The goal of our study is to determine the role of Rac-induced signaling in this transition process. Our previous results showed that Thyroxin (T4) treatment resulted in increased myocardial Rac expression in wild-type mice and a higher level of expression in Zea maize RacD (ZmRacD) transgenic mice. Our current results showed that T4 treatment induced physiologic cardiac hypertrophy in wild-type mice, as demonstrated by echocardiography and histopathology analyses. This was associated with significant increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Conversely, echocardiography and histopathology analyses showed that T4 treatment induced dilated cardiomyopathy along with compensatory cardiac hypertrophy in ZmRacD mice. These were linked with further increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Additionally, there were significant increases in caspase-8 expression and caspase-3 activity. However, there was a significant decrease in p38-MAPK activity. Interestingly, inhibition of myocardial Rac-GTP activity and superoxide generation with pravastatin and carvedilol, respectively, attenuated all functional, structural, and molecular changes associated with the T4-induced cardiomyopathy in ZmRacD mice except the compensatory cardiac hypertrophy. Taken together, T4-induced ZmRacD is a novel mouse model of dilated cardiomyopathy that shares many characteristics with the human disease phenotype. To our knowledge, this is the first study to show graded Rac-mediated O(2)·(-) results in cardiac phenotype shift in-vivo. Moreover, Rac-mediated O(2)·(-) generation, cardiomyocyte apoptosis, and myocardial fibrosis seem to play a pivotal role in the transition from cardiac hypertrophy to cardiac dilation and failure. Targeting Rac signaling could represent valuable therapeutic strategy not only in saving the failing myocardium but also to prevent this transition process.     

Role of adrenergic mechanisms in the development of cardiac hypertrophy.

This experiment was designed to study the role of cardiac beta-adrenergic mechanisms in the development of hypertrophy in rats. The suprarenal abdominal aorta was banded, resulting in an increase in cardiac wt-body wt ratio. A group of rats received a sham operation. Half of the banded rats were treated with practolol, 2.0 mg/kg intraperitoneally every 12 hr for the 6 days after banding. The effectiveness of cardiac beta-adrenergic blockade was confirmed by absence of an increase in heart rate following intravenous isoproterenol at various times between practolol injections. Practolol did not affect the gradient in the banded groups. Six animals in each banded group were sacrificed daily for 6 days. The right and left ventricles were dissected separately and weighed. RV-body weight ratios increased similarly in both banded groups. LV-body weight ratio (g/kg) was 2.17 +/- 0.043 in sham rats, and it attained maximal levels of 3.03 +/- 0.10 within 6 days in banded untreated rats and 2.96 +/- 0.14 in banded rats receiving practolol. Therefore, beta-adrenergic mechanisms were not involved in the development of hypertrophy due to increased afterload. Also, these findings are not consistent with the Meerson hypothesis, since hypertrophy occurred despite the reduction in myocardial O2 consumption due to practolol.     

Antihyperlipidaemic,Antihypertrophic, and Reducing Effects of Zingerone on Experimentally Induced Myocardial Infarcted Rats

The present study aims to evaluate the antihyperlipidaemic, antihypertrophic, and reducing effects of zingerone on isoproterenol‐induced hyperlipidaemia and hypertrophy in rats. Rats were pretreated with zingerone (6 mg/kg body weight) daily for a period of 14 days and then induced myocardial infarction with isoproterenol (100 mg/kg body weight) on days 15 and 16. Isoproterenol increased serum creatine kinase and lactate dehydrogenase activities in the rats. Increased levels/concentrations of serum and heart cholesterol and triglycerides were observed in isoproterenol‐induced myocardial infarcted rats. Isoproterenol also altered serum lipoproteins and the activity of liver 3‐hydroxy‐3‐methyl glutaryl‐coenzyme‐A‐reductase in the rats. The in vitro study revealed a very convincing reducing power of zingerone. Pretreatment with zingerone prevented hyperlipidaemia and cardiac hypertrophy, by virtue of its antihyperlipidaemic, antihypertrophic, and reducing properties in isoproterenol‐induced myocardial infarcted rats.     

Genistein prevents isoproterenol-induced cardiac hypertrophy in rats

Genistein, an isoflavone and a rich constituent of soy, possesses important regulatory effects on nitric oxide (NO) synthesis and oxidative stress. Transient and low release of NO by endothelial nitric oxide synthase (eNOS) has been shown to be beneficial, while high and sustained release by inducible nitric oxide synthase (iNOS) may be detrimental in pathological cardiac hypertrophy. The present study was designed to evaluate whether genistein could prevent isoproterenol-induced cardiac hypertrophy in male Wistar rats (150-200 g, 10-12 weeks old) rats. Isoproterenol (5 mg·(kg body weight)(-1)) was injected subcutaneously once daily for 14 days to induced cardiac hypertrophy. Genistein (0.1 and 0.2 mg·kg(-1), subcutaneous injection once daily) was administered along with isoproterenol. Heart tissue was studied for myocyte size and fibrosis. Myocardial thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), catalase levels, and 1-OH proline (collagen content) were also estimated. Genistein significantly prevented any isoproterenol-induced increase in heart weight to body weight ratio, left ventricular mass (echocardiographic), myocardial 1-OH proline, fibrosis, myocyte size and myocardial oxidative stress. These beneficial effects of genistein were blocked by a nonselective NOS inhibitor (L-NAME), but not by a selective iNOS inhibitor (aminoguanidine). Thus, the present study suggests that the salutary effects of genistein on isoproterenol-induced cardiac hypertrophy may be mediated through inhibition of iNOS and potentiation of eNOS activities.     

Cordycepin ameliorates cardiac hypertrophy via activating the AMPKα pathway

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'‐deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress‐dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after‐surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91^phox and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin‐treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post‐AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress.     

Involvement of Rho kinase pathway in the mechanism of renal vasoconstriction and cardiac hypertrophy in rats with experimental heart failure

Rho-dependent kinases serve as downstream effectors of several vasoconstrictor systems, the activities of which are upregulated in congestive heart failure (CHF). We evaluated renal and cardiac effects of Y-27632, a highly selective Rho kinase inhibitor, in an experimental model of volume-overload CHF. Effects of acute administration of Y-27632 (0.3 mg/kg) on renal hemodynamic and clearance parameters and effects of chronic treatment (10.0 mg.kg(-1).day(-1) for 7 days via osmotic minipumps) on cardiac hypertrophy and cumulative Na+ excretion were studied in male Wistar rats with aortocaval fistula and control rats. The Y-27632-induced decrease in renal vascular resistance (from 40.4 +/- 4.6 to 26.0 +/- 3.1 resistance units, P < 0.01) in CHF rats was associated with a significant increase in total renal blood flow (+34%) and cortical and medullary blood flow (approx +37 and +27%, respectively). These values were significantly higher than those in control rats and occurred despite a decrease in mean arterial pressure (-15 mmHg). Despite the marked renal vasodilatory effect, Y-27632 did not alter glomerular filtration rate and renal Na+ excretion. Chronic administration of Y-27632 did not alter daily or cumulative renal Na+ excretion in CHF rats but was associated with a significant decrease in heart-to-body weight ratio, an index of cardiac hypertrophy: 0.32 +/- 0.007, 0.46 +/- 0.017, and 0.37 +/- 0.006% in control, CHF, and CHF + Y-27632 rats, respectively. The findings suggest that Rho kinase-dependent pathways are involved in the mechanisms of renal vasoconstriction and cardiac hypertrophy in rats with volume-overload heart failure. Selective blockade of these signaling pathways may be considered an additional tool to improve renal perfusion and attenuate cardiac hypertrophy in heart failure.     

Cardiomegaly produced by chronic beta-adrenergic stimulation in the rat: comparison with alpha-adrenergic effects.

Chronic administration of d, l isoproterenol, 0.2 – 5 mg/kg/day, for 14–21 days in the male rat produced marked increases in dry ventricle weight (21.1 – 43.6%; p < 0.001). In comparison, an α-adrenergic agonist, phenylephrine (7.5 mg/kg/day) decreased ventricle weight (?15.3%; p < 0.025). Also, isoproterenol injection at 5 mg/kg/day decreased cardiac actomyosin ATPase activity by 23.3% (p < 0.0025) while phenylephrine, administered as above, did not influence ATPase activity. The effect of isoproterenol on heart weight was completely blocked by the β₁-adrenergic antagonist practolol (5 mg/kg/day). Albuterol, a relatively specific β₂-adrenergic agonist was less potent than isoproterenol in producing cardiac hypertrophy. l-Epinephrine injection, 0.8 mg/kg/day for 14 days, had no effect on heart weight. However, l-epinephrine produced cardiac hypertrophy (22.4% p < 0.001) when the animals were preinjected with the α-adrenergic antagonist, phenoxybenzamine (5 mg/kg/day). The data indicate that cardiac hypertrophy can be produced by stimulation of the β₁-adrenergic receptors of the heart; apparently, stimulation of α-adrenergic receptors opposes β-adrenergic hypertrophic effects.     

Metoprolol suppresses the development of ethanol-induced cardiac hypertrophy in the rat

Subacute, severe intoxication with ethanol stimulates the peripheral sympathetic nervous system in the rat and enhances the excretion of adrenaline and noradrenaline. In association with this effect there is a rapid development of cardiac hypertrophy, with proportional heart weight increasing by 12% within 48 h. At this time adrenal medullary adrenaline content was depressed by more than 35%, whereas nonadrenaline content of the adrenal and heart were not affected. Metoprolol (20 mg/kg, t.i.d.) was without effect when used alone and had little if any impact on the ethanol-induced changes. Metoprolol (100 mg/kg, t.i.d.) reduced adrenal catecholamine content, but not cardiac noradrenaline content, and diminished cardiac weight in control animals. The combination of ethanol with the high dose of methoprolol enhanced the loss of medullary catecholamine and reduced cardiac noradrenaline content, whereas cardiac weight was the same as in control animals. A correlation between sympathetic activation and increasing cardiac mass and its antagonism by metoprolol implies a beta-adrenoceptor mediated link in the cardiac hypertrophy induced by ethanol.     

The chemical chaperone 4-phenylbutyric acid attenuates pressure-overload cardiac hypertrophy by alleviating endoplasmic reticulum stress

Evidence has shown that endoplasmic reticulum stress (ERS) is associated with the pathogenesis of cardiac hypertrophy. The aim of this study was to investigate whether direct alleviation of ER stress by 4-phenylbutyric acid (PBA), a known chemical chaperone drug, could attenuate pressure-overload cardiac hypertrophy in mice. The effects of orally administered PBA (100mg/kg body weight daily for a week) were examined using mice undergoing transverse aortic constriction (TAC-mice), an animal model to produce pressure overload. TAC application for 1 week led to a 1.8-fold increase in the ratio of the heart weight over body weight (HW/BW) and up-regulation of the hypertrophy markers ANF and BNF accompanied by up-regulation of ERS markers (GRP78, p-PERK, and p-elF2α). The oral administration of PBA to the TAC-mice reduced hypertrophy (19%) and severely downregulated the fibrosis-related genes (transforming growth factor-β1, phospho-smad2, and pro-collagen isoforms). We conclude that ERS is induced as a consequence of remodeling during pathological hypertrophy and that PBA may help to relieve ERS and play a protective role against cardiac hypertrophy and possibly heart failure. We suggest PBA as a novel therapeutic agent for cardiac hypertrophy and fibrosis.     

Development of isoproterenol-induced cardiac hypertrophy

The development of cardiac hypertrophy was studied in adult female Wistar rats following daily subcutaneous injections of isoproterenol (ISO) (0.3 mg/kg body weight). A time course was established for the change in tissue mass, RNA and DNA content, as well as hydroxyproline content. Heart weight increased 44% after 8 days of treatment with a half time of 3.4 days. Ventricular RNA content was elevated 26% after 24 h of a single injection and reached a maximal level following 8 days of therapy. The half time for RNA accumulation was 2.0 days. The total content of hydroxyproline remained stable during the first 2 days of treatment but increased 46% after 4 days of therapy. Ventricular DNA content was unchanged during the early stage (1-4 days) of hypertrophic growth but increased to a new steady-state level 19% above the controls after 8 days of treatment. Intraventricular pressures and coronary flow measures were similar for control and experimental animals following 4 days of developed hypertrophy. However, dP/dt in the ISO-treated hearts was slightly but significantly (P less than 0.05) elevated. These data indicate that the adaptive response to ISO shows an early hypertrophic phase (1-4 days) characterized by a substantial increase in RNA content and cardiac mass in the absence of changes in DNA. However, prolonged stimulation (8-12 days) appears to represent a complex integration of both cellular hypertrophy and hyperplasia within the heart.     

Early ultrastructural changes in the myocardium following thyroxine-induced hypertrophy

The model of myocardial hypertrophy induced by thyroxine was studied with particular regard to the early ultrastructural changes in fractional volume of the mitochondria and myofibrils, and capillary distribution. Following injections of L-thyroxine (25 mg/kg IP) for 9 consecutive days, rats were sacrificed by vascular perfusion and cardiac tissue samples from the mid-wall zone of the left ventricle were processed routinely for electron microscopy. Heart weight/body weight ratios of thyroxine treated (T) rats showed a significant increase (P less than 0.001) over the ratios in control (C) rats. Likewise, the fractional volume of mitochondria (42%) was significantly increased (P less than 0.001) in the myocardium of T rats when compared with C rats (31%). However, the fractional volume of myofibrils was significantly decreased in the myocardium of T rats (P less than 0.001) and there was no significant difference between the hearts of T and C rats with respect to capillary luminal area/myocyte area. The mitochondria/myofibril ratio was increased in the hearts of T rats (0.82) over that found in control hearts (0.52). These results suggest that in the early stages of thyroxine-induced myocardial hypertrophy there is not an immediate increase in capillary area which may account for the ischemia and significant increase in mitochondrial volume which characterized myocardial hypertrophy in this model.     

Allicin protects against myocardial apoptosis and fibrosis in streptozotocin-induced diabetic rats

To evaluate the cardioprotective effect of allicin (AL) on myocardial injury of streptozotocin (STZ)-induced diabetic rats and to further explore its underlying mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (40 mg/kg). Three days after STZ induction, the hyperglycemic rats (plasma glucose levels ≥ 16.7 mmol/l) were treated with AL by intraperitoneal injection at the doses of 4 mg/kg, 8 mg/kg, and 16 mg/kg daily for 28 days. The fasting blood glucose levels were measured on every 7th day during the 28 days of treatment. The body weight, blood glucose, and parameter of cardiac function were detected after 4 weeks to study the cardioprotective effects of AL on diabetic rats in vivo. The apoptotic index of cardiomyocytes was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The expressions of Fas, Bcl-2, CTGF, and TGF-β(1) protein were studied by immunohistochemistry. Laser scanning confocal microscopy technique was utilized to observe the effects of AL on intracellular calcium concentration ([Ca(2+)](i)) in rat ventricular cardiomyocytes. AL at the doses of 4 mg/kg, 8 mg/kg, and 16 mg/kg significantly reduced blood glucose levels in a dose-dependent manner and increased body weight as well compared with the model group. Hemodynamic parameters including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximum rate of left ventricular pressure rise and fall (+dp/dtmax and -dp/dtmax) were significantly restored back to normal levels in AL-treated (8 mg/kg and 16 mg/kg) rats compared with diabetic model rats. AL markedly inhibited cardiomyocyte apoptosis induced by diabetic cardiac injury. Further investigation revealed that this inhibitory effect on cell apoptosis was mediated by increasing anti-apoptotic protein Bcl-2 and decreasing pro-apoptotic protein Fas. Additional experiments demonstrated AL abrogated myocardial fibrosis by blocking the expressions of CTGF and TGF-β(1) protein. AL shows protective action on myocardial injury in diabetic rats. The possible mechanisms were involved in reducing blood glucose, correcting hemodynamic impairment, reducing Fas expression, activating Bcl-2 expression, decreasing intracellular calcium overload, inhibiting the expressions of TGF-β(1) and CTGF, and further improving cardiac function.