Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.

[Progress on the role of Kalirin-7 in exercise intervention-mediated improvement of neurodegenerative diseases].

Guanine nucleotide exchange factor Kalirin-7 (Kal-7) is a key factor in synaptic plasticity and plays an important regulatory role in the brain. Abnormal synaptic function leads to the weakening of cognitive functions such as learning and memory, accompanied by abnormal expression of Kal-7, which in turn induces a variety of neurodegenerative diseases. Exercise can upregulate the expression of Kal-7 in related brain regions to alleviate neurodegenerative diseases. By reviewing the literature on Kal-7 and neurodegenerative diseases, as well as the research progress of exercise intervention, this paper summarizes the role and possible mechanism of Kal-7 in the improvement of neurodegenerative diseases by exercise and provides a new rationale for the basic and clinical research on the prevention and treatment of neurodegenerative diseases by exercise.

[Research progress of the role of IGF-1 in metabolic diseases and the effect of exercise intervention].

Insulin-like growth factor-1 (IGF-1) is a peptide with a similar molecular structure to insulin. IGF-1 plays a key role in tissue growth and development, as well as cell metabolism, proliferation, differentiation and apoptosis. Liver is the main source of IGF-1, with the production of IGF-1 up to 75% of the total in the whole body, while the remaining 25% are secreted by skeletal muscles, heart, kidney, spleen and other organs. Target organs of IGF-1 include heart, blood vessels, liver, bone and skeletal muscles. It has been well documented that IGF-1 plays an important role in the prevention and treatment of metabolic diseases. Different types of exercise have different effects on IGF-1 expression with organ differences. In this article, we reviewed the preventive and therapeutic effects of IGF-1 on metabolic diseases and IGF-1-mediated exercise-induced benefits.

[Research advance on cardiomyocyte proliferation induced by aerobic exercise and stem cell mobilization].

Appropriate exercise is the effective way for the prevention and treatment of heart diseases. Its mechanism has not been completely elucidated, and the safe and effective exercise prescription needs to be studied systematically. Exercises give rise to secretion of various cell factors, effective stem cell mobilization, physiological hypertrophy and differentiation and proliferation of cardiomyocytes. The cell sources of adult cardiomyocyte proliferation included viable cardiomyocytes, cardiac stem/progenitor cells, bone marrow stem cells, peripheral stem cells. Stem cell mobilization, homing and differentiation are the cellular basis of myocardial repair after injury. From the potential of cardiomyocyte proliferation, stem cell therapy after myocardial infarction and cardiac myocyte proliferation induced by exercise, this review focused on the stem cells mobilization promoted by aerobic exercise, the possible mechanism of cardiac repair and functional amelioration induced by the differentiation of those stem cells after myocardial infarction, the problems remained to be further studied and correlative research progress.

[Research advance on angiogenesis in ischemic heart induced by aerobic exercise and stem cell mobilization].

Aerobic exercise has specific angiogenesis effect, also in the ischemic heart. But its mechanism has not been fully clarified. Coronary microvascular angiogenesis is the precondition of heart repair after myocardial infarction (MI). Recent studies have shown that angiogenesis is caused by endogenous stem cell/progenitor mobilization and participation, and its paracrine effects on endothelial cells (EC) function and microvascular distribution. Exercise could mobilize and activate the expression and secretion of endogenous stem cell and angiogenic factors, and affect the cardiac angiogenesis in epigenetics. Investigating the effect of different exercise methods and intension on ischemic cardiac angiogenesis and its molecular mechanism are of great significance on prevention and postoperative rehabilitation of MI. This review summarized the main mechanism, existing problems and related research progress on exercise improving ischemic cardiac angiogenesis through cardiac angiogenesis and its regulation mechanisms, endogenous stem cell mobilization and participates in angiogenesis of ischemic heart, and exercise improving ischemic cardiac angiogenesis through stem cell mobilization.

[Exercise intervention in skeletal muscle endocrine function].

As a new secretory organ skeletal muscle, which could secrete a variety of biological active substances, plays an important role in biological function and clinical medicine, and has important research value and application scenarios in the field of sports medicine. Different mode and intensity of exercise would give different influences on skeletal muscle endocrine function. Exercise intervention could improve the chronic disease, such as metabolic disease (obesity, diabetes) and muscle atrophy by changing endocrine function of the skeletal muscle. It will be great valuable to explore the mechanisms of exercise-induced skeletal muscle endocrine, seek for the appropriate biomarker, make exercise prescription, which would give improtant theoretical value and application prospect for the exercise system function improvement metabolic disease grevention and exercise rehabilitation of the systemic diseases.

[Effects of aerobic interval training on myocardial oxidative stress and inflammation in rats with myocardial infarction and its mechanism].

Objective: The present study was to determine the effects of aerobic interval training (AIT) on the expressions of SIRT1, Nox4 and inflammatory factor in the heart of rats with myocardial infarction (MI). Methods: Male Sprague Dawley rats were randomly divided into sham-operated group (C), sedentary MI group (MI) and MI with AIT group (ME) (n=10). The MI model was established by ligation the left anterior descending coronary artery. Rats in C groups were subjected to the same surgery, but only threaded and not ligated. After surgery 1 week, rats in ME groups took adaptability training for 1 week, and then subjected to 4 weeks treadmill exercise training. After training, the hearts were collected for histological observation. The level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in heart was assessed by ultraviolet spectrophotometry. The activity of lactate dehydrogenase (LDH) was determined by enzyme linked immunosorbent assay. The expression of sirtuin1 (SIRT1) mRNA was examined by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of SIRT1, NADPH oxidase 4 (Nox4), tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß) were detected by Western blotting. The levels of reactive oxygen species (ROS) were detected by dihydroethidium (DHE) staining. Results: Compared with the C group, the expression level of cardiac Nox4 protein was increased (P＜0.01), the level of MDA, activity of LDH and the level of ROS were increased significantly (P＜0.01), and the expressions of TNF-α and IL-1ß protein were augmented in the heart of rats with MI (P＜0.01). However, the expressions of SIRT1 mRNA and protein and the activity of SOD were obviously decreased in MI group (P＜0.01). Furthermore, compared with the MI group, AIT increased the expressions of SIRT1 mRNA and protein and the activity of SOD in the heart of ME group (P＜0.01); Meanwhile, the expressions of cardiac Nox4, MDA level, LDH activity and ROS level were diminished in ME group (P＜0.01) as well as the decreased expressions of TNF-α and IL-1ß protein (P＜0.01). SIRT1 expression was negatively related to the expressions of NOX4 and ROS. Conclusion: AIT obviously inhibited myocardial oxidative stress and inflammatory reaction, improved cardiac function in rats with MI, and the mechanism was closely related to the activation of SIRT1-Nox4-ROS signaling pathway.

Exercise benefits cardiovascular health in hyperlipidemia rats correlating with changes of the cardiac vagus nerve.

The role of exercise training on hemodynamic parameters, blood lipid profiles, inflammatory cytokines, cholinesterase-positive nerves and muscarinic cholinergic (M(2)) receptors expression in the heart was investigated in Sprague-Dawley male rats with hyperlipidemia (HL). The rats were subjected to a high-fat diet and exercise training for 8 weeks, and then the hemodynamic parameters, the profiles of blood lipid and inflammatory cytokines, and the expression of cholinesterase-positive nerves and M(2) receptors were measured. HL rats displayed cardiac dysfunction, dysregulation of inflammatory cytokines, and decreased cholinesterase-positive nerves and M(2) receptors expression. The combination of hyperlipidemia with exercise training (AT) restored the profiles of blood lipids and the levels of inflammatory cytokines. In addition, AT and HL + AT improved cardiac function with increasing cholinesterase-positive nerves and M(2) receptors expression. Overall, these data show that the increased expression of cholinesterase-positive nerves and M(2) receptors in the heart is partially responsible for the benefits of exercise training on cardiac function in hyperlipidemia rats.

Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin.

Aging is an independent risk factor for hypertension, and hypertension and insulin resistance commonly coexist in the elderly. This study was designed to examine the effects of aging-related insulin resistance on blood pressure (BP) and its underlying mechanisms, with specific focus on the role of exercise in reversing hypertensive response. Adult (6-month-old) and aging (24-month-old) male Sprague-Dawley rats were subjected to a 10 weeks free-of-loading swim training (60 min/day, 5 days/week). Arterial vasorelaxation, cardiac contraction, eNOS activation, and iNOS and gp91(phox) expression were determined. Under aging-related insulin resistance conditions, insulin infusion significantly elevated BP (P < 0.05). Aging caused significant endothelial dysfunction (P < 0.05 - 0.01), which was responsible for decreased arterial vasorelaxation to insulin. Aging attenuated myocardial contractile response to insulin, decreased eNOS expression and its phosphorylation by insulin, and increased iNOS and gp91(phox) expression in aging arteries (P < 0.01). Exercise improved insulin sensitivity, potentiated insulin's positive inotropic effects, facilitated arterial vasorelaxation to insulin, increased arterial eNOS activation in adult and aging rats, and thus attenuated insulin resistance-related hypertensive response to insulin. Moreover, exercise markedly reversed increased iNOS and gp91(phox) expression in aging arteries. Inhibition of eNOS with Cavtratin or L-NAME significantly blocked exercise-facilitated arterial vasorelaxation to insulin and exercise-lowered BP response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin, but not insulin's positive inotropic effects, plays an important role in the development of aging-related hypertension. The reversal of hypertensive response to insulin by exercise is most likely associated with improved insulin sensitivity in an eNOS-dependent manner and reduced oxidative and nitrative stresses.

[Synthesis, solubility, lipids-lowering and liver-protection activities of sulfonated formononetin].

A water-soluble compound, sodium formononetin-3'-sulfonate with good lipid-lowering and liver-protection activities was synthesized. It was synthesized by sulfonation reaction, and its structure was characterized by IR, NMR and elemental analyses. The solubility of sodium formononetin-3'-sulfonate in water and n-octanol/water partition coefficient were determined by UV spectrophotometry. The lipid-lowering and liver-protection activities of sodium formononetin-3'-sulfonate were tested by using rat's high fat model induce by feeding with high fat food. The results showed that sodium formononetin-3'-sulfonate not only had favorable water, solubility but also had good lipid-lowering and liver-protection activities.

[Effects of interval training on calcium transient and contractile function of single ventricular myocyte in myocardial infarction adult rats].

OBJECTIVE: To investigate the effects of interval training on calcium transient and contractile function in ischemic ventricular myocytes of rats with myocardial infarction and their synchronization. METHODS: Twenty-four male sprague-dawley rats in three years old, were randomly divided into three groups (n=8): sham-operated group(S), sedentary MI group(MI) and MI with interval training group (ME). The MI model was established by ligation of the left anterior descending coronary artery. The rats in ME group started training 1 week after MI operation. The S model was established by threading only without ligation. ME model took one week adaptive training, 10 m/min and 30 min/d, then took subsequently 8-week aerobic interval training: 10 min×10 m/min, then reran the rats with 2 intensities 15 m/min×6 min and 25 m/min×4 min, 1 h/d, 5 d/week. After training 24 hours, the cardiomyocytes of all groups were isolated by using the Langendorff fusion system. The contractile function and calcium transient of single ventricular myocyte in myocardial infarction adult rats were detected by IonOptix. Calcium transients were measured as [Ca2+]i amplitude, departure velocity, ratio, TTB50％, TTP and TTP50%, return velocity and ratio amplitude. PTA, SL, ±dl/dtmax and SL shortening% were tested to evaluate contractility. RESULTS: Compared with S, the levels of [Ca2+]i amplitude, departure velocity, ratio amplitude and return velocity, SL shortening%, PTA and ±dl/dtmax of MI were decreased(P＜0.01), the levels of TTP, TTP50% and TTB50% of MI were increased(P＜0.01); Compared with MI, the levels of departure velocity, ratio amplitude, return velocity and [Ca2+]i amplitude of ME were increased(P＜0.01), the levels of TTB50%, TTP and TTP50% of ME were decreased(P＜0.01, P＜0.05). The levels of SL shortening%, PTA and ±dl/dtmax of ME were increased(P＜0.01, P＜0.05). CONCLUSION: Interval training can improve calcium transient and contractile function of single ventricular myocyte in myocardial infarction adult rats.

[Effect of aerobic interval training on the expression of renal CD40 in a rat model with myocardial infarction and its mechanism].

OBJECTIVE: To study the effects of aerobic interval training (AIT) on renal cluster of differentiation 40 (CD40) expression in rats with myocardial infarction (MI) and its possible mechanism. METHODS: Thirty-six rats were randomly divided into three groups (n=12):Sham, MI and MI with AIT (ME) groups. The MI model was established by ligation of the left anterior descending coronary artery. Treadmill training was performed five times a week for 8 weeks (AIT:60 min/day with 10 min of warm-up at 10 m/min and 50 min of exercise at 25 m/min 7 min interspersed with 3 min at 15 m/min). After training, cardiaorenal function and renal tissue remodeling were evaluated. The changes of CD40, high-sensitivity C reactive protein(hs-CRP), TNF-α, IL-6, p-NF-κBp65, blood urea nitrogen (BUN) and serum creatinine (sCr) were determined. RESULTS: Compared with the sham group, MI significantly increased left ventricular end-diastolic pressure (LVEDP) and decreased left ventricular systolic pressure (LVSP) and left indoor pressure change rate peak (dp/dtmax) in the MI group, concomitant with the increase in renal collagen volume fraction (CVF), which was reversed by AIT in the ME group. Moreover, compared with the sham group, CD40 was largely dispersed within the cytoplasm of renal tubule cells in the MI group. Meanwhile, the expressions of renal CD40 mRNA and protein, the levels of serum and renal hs-CRP, TNF-α and IL-6, the phosphorylation of NF-κBp65 (p-NF-κBp65) and the levels of sCr and BUN were obviously increased in the MI group. Compared with the MI group, AIT decreased the expressions of renal CD40 mRNA and protein, the levels of serum and renal hs-CRP, TNF-α and IL-6 and the expression of p-NF-κBp65, as well as decreased the levels of sCr and BUN in the ME group. CONCLUSIONS: AIT reduces the expressions of renal CD40 protein and mRNA, inhibits NF-κB signaling pathway, and then decreases the levels of inflammatory factors thereby improve the renal dysfunction after MI.

SIRT1 regulates lipopolysaccharide-induced CD40 expression in renal medullary collecting duct cells by suppressing the TLR4-NF-κB signaling pathway.

AIMS: Recent evidence indicates that sirtuin1 (SIRT1), an NAD+-dependent deacetylase, exerts a protective effect against inflammatory kidney injury by suppressing pro-inflammatory cytokines production. The co-stimulatory molecule, CD40, is expressed in a variety of inflammatory diseases in the kidney. Here, we aimed to investigate the potential effect of SIRT1 on CD40 expression induced by lipopolysaccharide (LPS) and to disclose the underlying mechanisms in renal inner medullary collecting duct (IMCD) cells. MAIN METHODS: mRNA and protein expressions were identified by quantitative real-time PCR and Western blot respectively. Subcellular localization of SIRT1 and CD40 were respectively detected by immunofluorescence and immunohistochemical staining. Small-interfering RNA (siRNA) was carried out for mechanism study. KEY FINDINGS: LPS reduced SIRT1 expression and up-regulated the expression of CD40, Toll-like receptor 4 (TLR4) and phospho-NF-κBp65 (p-NF-κBp65) in time- and concentration-dependent manners. Moreover, SIRT1 overexpression or activation by SRT1720 diminished the expression of CD40, TLR4 and p-NF-κBp65, which was reversed by SIRT1 siRNA or inhibitors Ex527 and sirtinol in LPS-stimulated IMCD cells. In addition, knockdown of TLR4 decreased the expression of CD40 and p-NF-κBp65 in IMCD cells exposed to LPS. Knockdown of NF-κBp65 or NF-κBp65 inhibition by pyrrolidine dithiocarbamate (PDTC) reduced LPS-induced CD40 expression in IMCD cells. Importantly, the inhibitory effect of SIRT1 on the expression of CD40 and p-NF-κBp65 was augmented by pre-treating with TLR4 siRNA. SIGNIFICANCE: Our data indicate that SIRT1 inhibits LPS-induced CD40 expression in IMCD cells by suppressing the TLR4-NF-κB signaling pathway, which might provide novel insight into understanding the protective effect of SIRT1 in kidney.

Cardiac muscle sarcolemma chromatographic stationary phase and its potential application in drug screening.

A new bioactive packing material for liquid chromatography, sarcolemma chromatography stationary phase (SCSP), is presented. Its surface characteristics are investigated, and it is found that the acceptors embedded in sarcolemma remained bioactive for more than a week. The retention behavior of antagonists and activators related to cardiac muscle sarcolemma on the SCSP chromatographic column shows the screening function of the SCSP column, and the retention behavior of the active components in the aether extract from the Chinese herb Ligusticum chuanxiong Hort. on the SCSP column reveals, to a certain extent, the separation function of the SCSP column. These suggest that SCSP is a potentially useful material in drug screening.

Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model.

AIMS: Exercise training (ET) has a cardioprotective effect and can alter the molecular response to myocardial infarction (MI). The Neuregulin 1 (NRG1)/ErbB signaling plays a critical role in cardiac repair and regeneration in the failing heart. We sought to investigate whether ET following MI could activate the NRG1/ErbB signaling and promote cardiac repair and regeneration. MAIN METHODS: Male Sprague-Dawley rats were used to establish the MI model. Exercise-trained animals were subjected to four weeks of exercise (16m/min, 50min/d, 5d/wk) following the surgery. AG1478 was used as an inhibitor of ErbB (1mg/kg body weight, administered i.v. every other day during the process of training). NRG1/ErbB signaling activation, cardiomyocyte (CM) proliferation and apoptosis were evaluated. KEY FINDINGS: In the exercise-trained rats, NRG1 expression was up-regulated and ErbB/PI3K/Akt signaling was activated compared with the MI group. In addition, ET preserved heart function accompanied with increased numbers of BrdU(+) CMs, PCNA(+) CMs and c-kit(+) cells, and reduced apoptosis level in the MI rats. In contrast, blocking ErbB signaling by AG1478 attenuated the ET-induced cardiac repair and regeneration. SIGNIFICANCE: ET up-regulates NRG1 expression and activates ErbB2, ErbB4 and PI3K/Akt signal transduction to promote cardiac repair through endogenous regeneration. Activation of ErbB may be an underlying mechanism for the ET-induced cardiac repair and regeneration following MI.

[Study on the interactions between Ligusticum chuanxiong extract and cardiac muscle membrane receptors by CMSP chromatography].

OBJECTIVE: To study the interactions between Ligusticum chuanxiong Hort extract and cardiac muscle membrane receptors. METHOD: The cell membrane of rabbit cardiac muscle was fixed on silicon to make cell membrane stationary phase (CMSP), and then the interactions were studied by comparing the retention characteristics of the extracts from different solvents with those of the antagonists or activators corresponding to known receptors in cardiac muscle membrane, and by competition effect on the retention characteristics of extracts when adding the antagonists or activators into the mobile phase. RESULT: Water extract and ethanol extract both had retentions on CMSP; the retention characteristics of water extract could be affected when water extract was in competition with the antagonists for alpha receptor, and could not be affected when with the activator beta1 receptor. CONCLUSION: It is possible that some components in water extract may combine with alpha receptor and no component with beta1 receptor, and that some components in ethanol extract may combine with cardiac muscle cell membrane. The process between active components and receptors in vivo can be imitated through the interactions between drugs and CMSP. The method provides references for the resolution of two applications: to screen the active components from Chinese medicine, and to figure out the type of receptors involved.

[Screening models and techniques for medicine and its application in the studies on the active components of Chinese medicine].

The development of modern biologic techniques have provided new techniques and approaches for the modern studies on active components of Chinese medicine. This article is a review of four kinds of screening models and corresponding techniques for medicine and their applications in the studies on the active components of Chinese medicine. The four aspects comprise the whole animal models, receptor models and molecular biochromatography, cell models and cell membrane chromatography, and gene chip techniques. It will provide references for promoting studies and accelerating modernization of Chinese medicine.

Aerobic exercise inhibits sympathetic nerve sprouting and restores ß-adrenergic receptor balance in rats with myocardial infarction.

BACKGROUND: Cardiac sympathetic nerve sprouting and the dysregulation of ß-adrenergic receptor (ß-AR) play a critical role in the deterioration of cardiac function after myocardial infarction (MI). Growing evidence indicates that exercise provides protection against MI. The aims of this study were to investigate whether aerobic exercise following MI could inhibit sympathetic nerve sprouting and restore the balance of ß3-AR/ß1-AR. METHODS: Male Sprague-Dawley rats were divided into three groups: sham-operated control group (SC), MI group (MI), and MI with aerobic exercise group (ME). The rats in ME group were assigned to 8 weeks of exercise protocol (16 m/min, 50 min/d, 5 d/wk). The expression of nerve growth factor (NGF), the sympathetic nerve marker-tyrosine hydroxylase (TH), the nerve sprouting marker-growth associated protein 43 (GAP43), and ß1- and ß2-AR expression in the peri-infarct area of the left ventricle (LV) were measured by Western blot and immunohistochemistry, while ß3-AR expression was determined by Western blot and immunofluorescence. Endothelial nitric oxide synthase (NOS2), phospho-NOS2 (p-NOS2), and neuronal nitric oxide synthase (NOS1) were measured by Western blot. RESULTS: MI increased LV end-diastolic pressure (LVEDP), and decreased LV systolic pressure (LVSP). Compared with the MI group, aerobic exercise significantly decreased LVEDP and increased LVSP. The protein expression of TH, GAP43 and NGF was significantly increased after MI, which was normalized by exercise. Compared with the SC group, the ratios of ß2-AR/ß1-AR and ß3-AR/ß1-AR were elevated in the MI group, and the protein expression of ß3-AR and NOS1 increased after MI. Compared with the MI group, the ratios of ß2-AR/ß1-AR and ß3-AR/ß1-AR were normalized in the ME group, while the protein expression of ß3-AR and NOS1 significantly increased, and NOS2 was activated by exercise. CONCLUSIONS: Aerobic exercise inhibits cardiac sympathetic nerve sprouting, restores ß3-AR/ß1-AR balance and increases ß3-AR expression through the activation of NOS2 and NOS1 after myocardial infarction.

Exercise training attenuates hypertension and cardiac hypertrophy by modulating neurotransmitters and cytokines in hypothalamic paraventricular nucleus.

AIMS: Regular exercise as an effective non-pharmacological antihypertensive therapy is beneficial for prevention and control of hypertension, but the central mechanisms are unclear. In this study, we hypothesized that chronic exercise training (ExT) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and restoring the neurotransmitters balance in the hypothalamic paraventricular nucleus (PVN) in young spontaneously hypertensive rats (SHR). In addition, we also investigated the involvement of nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in exercise-induced effects. METHODS AND RESULTS: Moderate-intensity ExT was administrated to young normotensive Wistar-Kyoto (WKY) and SHR rats for 16 weeks. SHR rats had a significant increase in mean arterial pressure and cardiac hypertrophy. SHR rats also had higher levels of glutamate, norepinephrine (NE), phosphorylated IKKß, NF-κB p65 activity, NAD(P)H oxidase subunit gp91(phox), PICs and the monocyte chemokine protein-1 (MCP-1), and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN. These SHR rats also exhibited higher renal sympathetic nerve activity (RSNA), and higher plasma levels of PICs, and lower plasma IL-10. However, ExT ameliorates all these changes in SHR rats. CONCLUSION: These findings suggest that there are the imbalances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN of SHR rats, which at least partly contributing to sympathoexcitation, hypertension and cardiac hypertrophy; chronic exercise training attenuates hypertension and cardiac hypertrophy by restoring the balances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN; NF-κB and oxidative stress in the PVN may be involved in these exercise-induced effects.

Protective effects of apricot kernel oil on myocardium against ischemia-reperfusion injury in rats.

The present study was undertaken to evaluate the potential cardioprotective effects of apricot kernel oil (AO) on the myocardial ischemia-reperfusion (IR) of rat model in vivo. The rats were divided into five groups: sham-operated, IR, low dose AO-treated IR (LD-AO+IR), medium dose AO-treated IR (MD-AO+IR) and high dose AO-treated IR (HD-AO+IR). All rats were provided with food and water ad libitum. The LD-AO+IR, MD-AO+IR and HD-AO+IR groups were given a daily dose of 2, 6 and 10 ml kg(-1)BW(-1) of AO, respectively, for 14 days prior to the IR operation. Tetrazolium chloride staining revealed that infarct size and the ratio of infarct weight to the total heart weight were decreased significantly in the three AO-treated groups compared to the IR group. The serum creatine kinase and aspartate aminotransferase activities also demonstrated similar beneficial effects. Myocardial catalase, superoxide dismutase, glutathione peroxidase, and constitutive nitric oxide synthase activities, as well as NO concentrations, were all increased, whereas malondialdehyde content and inducible nitric oxide synthase were decreased in AO-treated rats. These findings suggest that apricot kernel oil has potent cardioprotective effects, and could be developed as a nutriment for the treatment and prevention of myocardial infarcts.