scholarly journals Ultrasound-targeted microbubble destruction promotes myocardial angiogenesis and functional improvements in rat model of diabetic cardiomyopathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xijun Zhang ◽  
Xinqiao Tian ◽  
Peng Li ◽  
Haohui Zhu ◽  
Nanqian Zhou ◽  
...  

Abstract Background Microvascular insufficiency plays an important role in the development of diabetic cardiomyopathy (DCM), therapeutic angiogenesis has been mainly used for the treatment of ischemic diseases. This study sought to verify the preclinical performance of SonoVue microbubbles (MB) combined ultrasound (US) treatment on myocardial angiogenesis in the rat model of DCM and investigate the optimal ultrasonic parameters. Methods The male Sprague–Dawley (SD) rats were induced DCM by streptozotocin through intraperitoneal injecting and fed with high-fat diet. After the DCM model was established, the rats were divided into the normal group, DCM model group, and US + MB group, while the US + MB group was divided into four subsets according to different pulse lengths (PL) (8 cycles;18 cycle;26 cycle; 36 cycle). After all interventions, all rats underwent conventional echocardiography to examine the cardiac function. The rats were sacrificed and myocardial tissue was examined by histology and morphometry evaluations to detect the myocardial protective effect of SonoVue MBs using US techniques. Results From morphologic observation and echocardiography, the DCM rats had a series of structural abnormalities of cardiac myocardium compared to the normal rats. The US-MB groups exerted cardioprotective effect in DCM rats, improved reparative neovascularization and increased cardiac perfusion, while the 26 cycle group showed significant therapeutic effects on the cardiac functions in DCM rats. Conclusion This strategy using SonoVue MB and US can improve the efficacy of angiogenesis, even reverse the progress of cardiac dysfunction and pathological abnormalities, especially using the 26 cycle parameters. Under further study, this combined strategy might provide a novel approach for early intervention of DCM in diabetic patients.

2020 ◽  
Author(s):  
Xijun Zhang ◽  
Haohui Zhu ◽  
Nanqian Zhou ◽  
Zhixin Fang ◽  
Yuping Yang ◽  
...  

Abstract Objective: Microvascular insufficiency takes a critical role in the development of diabetic cardiomyopathy (DCM), therapeutic angiogenesis has been mainly used for the treatment of ischemic diseases. The present study sought to investigate the preclinical performance of SonoVue microbubbles(MBs) combined ultrasound(US) treatment on myocardial angiogenesis in a rat model of DCM and investigate the optimal ultrasonic parameters.Methods and Results: After the DCM model was established, the cardio protective effect of SonoVue MBs using US techniques was examined by histology, morphometry, and echocardiography evaluations. From morphologic observation and echocardiography, the DCM rats had a set of structural abnormalities in the heart compared to the normal rats. The US-MB groups exerted cardio protective effect in DCM rats, improved reparative neovascularization and increased cardiac perfusion, while the 26 cycle group showed significantly therapeutic effects on the cardiac functions in DCM rats.Conclusion: This strategy using SonoVue MB and US can significantly improve or even reverse cardiac dysfunction and pathological abnormalities, especially using the 26 cycle parameters. Under further study, this combined strategy might provide a novel approach for early intervention of DCM in diabetic patients.


2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Naness EL-Malkey ◽  
Mariam Michael ◽  
Maher Ibrahim ◽  
Rania Said Moawad ◽  
Maha Abdul Rahman ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 343 ◽  
Author(s):  
Eunjin Sohn ◽  
Yu Kim ◽  
Hye-Sun Lim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong

Hwangryunhaedok-tang (HRT) is a traditional oriental herbal formula used in Asian countries for treating inflammatory diseases and controlling fever. Our present study aimed to determine whether HRT has therapeutic effects for patients with vascular dementia (VaD) using a bilateral common carotid artery occlusion (BCCAO) rat model and assessing spatial memory impairment and activation of neuroinflammation. BCCAO was performed in male Sprague Dawley rats to induce VaD, and oral HRT was administered daily for 30 d. Our data showed that HRT ameliorated BCCAO-induced memory and cognitive impairment in behavioral tests. In addition, HRT reversed cholinergic dysfunction and neuronal damage in the hippocampus of BCCAO rats. Furthermore, HRT attenuated microglial activation and reduced the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK) induced by BCCAO. Simultaneous high-performance liquid chromatography analysis of HRT using index compounds from the herbal composition revealed that both HRT ethanol extract and commercial HRT granules primarily comprise geniposide, baicalin, and berberine. Our study showed that HRT administration resulted in the prevention of neuronal injury induced by BCCAO through improvement of cholinergic dysfunction and inhibition of neuroinflammatory responses, suggesting that HRT may have potential as a treatment for VaD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rania M. Magadmi ◽  
Mujahid A. Alsulaimani ◽  
Aziza R. Al-Rafiah ◽  
Muhammad Saeed Ahmad ◽  
Ahmed Esmat

Diabetic neuropathy (DN) commonly occurs in diabetics, affecting approximately 50% of both type 1 and 2 diabetic patients. It is a leading cause of non-traumatic amputations. Oxidative stress could play a key role in the pathophysiology of DN. This study aimed to investigate the potential neuroprotective effect of carvedilol on STZ-induced DN in rats. Thirty male Sprague Dawley rats (weighing 200–250 g) were randomly divided into five groups (six/group), where group 1 (negative control) received only the vehicle (0.5% of carboxymethyl cellulose orally 1 ml/kg). DN was induced by a single injection of remaining rats with streptozotocin (STZ; 50 mg/kg, i.p.). After diabetes induction, group 2 served as the diabetic untreated animals; while groups 3 and 4 were treated with carvedilol (1 and 10 mg/kg/d, orally, respectively). Group 5 received a-lipoic acid as a reference neuroprotective (100 mg/kg/d, orally). All treatments were continued for 45 days after diabetes induction, followed by behavioural tests. After sacrificing the animals, dorsal root ganglia, and sciatic nerves were collected for histopathological examination and biochemical assessments. Briefly, STZ administration caused cold allodynia, induced oxidative stress, and increased nerve growth factor (NGF) concentration. Nevertheless, carvedilol improved the behavioural tests, ameliorated the oxidative imbalance as manifested by reducing malondialdehyde, restoring glutathione content, and superoxide dismutase activity. Carvedilol also decreased NGF concentration in DRG homogenate. In conclusion, this study demonstrates the neuroprotective effect of carvedilol in an experimentally induced DN rat model through–at least partly–its antioxidant effect and reduced NGF concentration in DRG.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ying-Ying Tan ◽  
Lei-Xin Chen ◽  
Ling Fang ◽  
Qi Zhang

Abstract Background Diabetic cardiomyopathy is a main cause of the increased morbidity in diabetic patients, no effective treatment is available so far. Polydatin, a resveratrol glucoside isolated from the Polygonum cuspidatum, was found by our and others have antioxidant and cardioprotective activities. Therapeutic effects of polydatin on diabetic cardiomyopathy and the possible mechanisms remains unclear. This study aimed to investigate the cardioprotective effects and underlying mechanisms of polydatin on myocardial injury induced by hyperglycemia. Methods Diabetes in rats was made by high-fat diet combined with multiple low doses of streptozotocin, and then treated with polydatin (100 mg·kg-1·day-1, by gavage) for 8 weeks. Cardiac function was examined by echocardiography. Myocardial tissue and blood samples were collected for histology, protein and metabolic characteristics analysis. In cultured H9c2 cells with 30 mM of glucose, the direct effects of polydatin on myocyte injury were also observed. Results In diabetic rats, polydatin administration significantly improved myocardial dysfunction and attenuated histological abnormalities, as evidenced by elevating left ventricular shortening fraction and ejection fraction, as well as reducing cardiac hypertrophy and interstitial fibrosis. In cultured H9c2 cells, pretreatment of polydatin dose-dependently inhibited high glucose-induced cardiomyocyte injury. Further observation evidenced that polydatin suppressed the increase in the reactive oxygen species levels, NADPH oxidase activity and inflammatory cytokines production induced by hyperglycemia in vivo and in vitro. Polydatin also prevented the increase expression of NOX4, NOX2 and NF-κB in the high glucose -stimulated H9c2 cells and diabetic hearts. Conclusions Our results demonstrate that the cardioprotective effect of polydatin against hyperglycemia-induced myocardial injury is mediated by inhibition of NADPH oxidase and NF-κB activity. The findings may provide a novel understanding the mechanisms of the polydatin to be a potential treatment of diabetic cardiomyopathy.


2013 ◽  
Vol 114 (3) ◽  
pp. 402-410 ◽  
Author(s):  
Yao-Te Huang ◽  
Chun-Hsu Yao ◽  
Chia-Li Way ◽  
Kung-Wei Lee ◽  
Cheng-Yen Tsai ◽  
...  

Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.


2018 ◽  
Vol 96 (12) ◽  
pp. 1197-1208
Author(s):  
Manal Moustafa Mahmoud ◽  
Asmaa Mohammed Shamseldeen ◽  
Laila Ahmed Rashed ◽  
Amal Elham Fares ◽  
Ashraf Shamaa ◽  
...  

Volume overload is a common phenomenon in patients with chronic kidney disease that is associated with cardiovascular risk factors. However, its contribution to the development of adverse cardiovascular outcomes in those patients is not fully understood. Thus, the present work investigated the effect of salt-induced volume overload on cardiac functions and geometry in a rat model of chronic kidney disease. Thirty adult male Sprague–Dawley rats were randomly divided. One set of animals received a sham operation, while another set of animals underwent uninephrectomy. Rats were then fed either a normal-salt (0.4%) or high-salt (8.0%) diet for 6 weeks. The salt-loaded, uninephrectomized rats were treated with indapamide (3 mg·kg–1·day–1, orally) for 6 weeks. We found that uninephrectomized rats subjected to a high-salt diet (8.0%) for 6 weeks presented with hypertension, proteinuria, decreased renal Klotho expression, and deterioration in cardiac hemodynamics and histology. Echocardiography to assess cardiac function showed that ejection fraction and fractional shortening were positively correlated with relative renal Klotho expression. In conclusion, salt-induced volume overload in a rat model of chronic kidney disease has an adverse cardiovascular outcome and is associated with inflammatory activation and decrease in renal Klotho expression.


2021 ◽  
Author(s):  
Se Ho Kim ◽  
Jae Yeon Kim ◽  
Soo Young Park ◽  
Won Tae Jeong ◽  
Jin Man Kim ◽  
...  

Abstract Background: Accumulation of cholesterol and depletion of calcium induce hepatic injury through the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. Previously, we reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL-1) promoted liver regeneration through mitochondrial dynamics in a cirrhotic rat model. However, whether PRL-1 is involved in ER stress-dependent calcium is unclear. So, we demonstrated that PD-MSCsPRL-1 improves hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL). Methods: Liver cirrhosis was induced in Sprague-Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL-1 (2x106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL-1. Results: ER stress markers (e.g., eIF2α, ATF4, and CHOP) were increased in the non-transplantation group (NTx) compared with the control group. PD-MSCsPRL-1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers (e.g., SERCA2b, IP3R, MCU, and VDAC1) (*p<0.05). In TG-treated WB-F344 cells, cocultivation with PD-MSCsPRL-1 decreased cytosolic CaM expression and cytosolic and mitochondrial Ca2+ concentrations; however, the ER Ca2+ concentration was increased compared to that in PD-MSCs (*p<0.05). Additionally, PRL-1 through epidermal growth factor receptor (EGFR) activated phosphatidylinositol-3-kinase (PI3K) signaling, resulting in calcium increases via CaM expression. Conclusions: These findings suggest that PD-MSCsPRL-1 improved hepatic functions through calcium changes and attenuated ER stress in a BDL-injured rat model. Therefore, these results provide useful data for the development of next-generation MSC-based stem cell therapy for regenerative medicine in chronic liver disease.


2018 ◽  
Vol 36 (4) ◽  
pp. 254-260 ◽  
Author(s):  
Xiaojia Li ◽  
Xiutian Guo ◽  
Weiqi Jin ◽  
Jingen Lu

Background Bone marrow mesenchymal stem cells (BMSCs) and acupuncture are known to mitigate tissue damage. This study aimed to investigate the therapeutic effects of combined electroacupuncture (EA) stimulation and BMSC injection in a rat model of anal sphincter injury-induced faecal incontinence (FI). Methods 60 Sprague-Dawley rats were randomly divided into five groups: sham-operated control, FI, FI+EA, FI+BMSC, and FI+BMSC+EA. The anorectal tissues were collected on days 1, 3, 7 and 14. Repair of the injured anal sphincter was compared using haematoxylin and eosin (HE) and immunocytochemiscal analyses with sarcomeric α actinin. The expression of stromal cell derived factor-1 (SDF-1) and monocyte chemoattractant protein-3 (MCP-3) was detected by quantitative reverse transcription PCR to evaluate the effects of EA on the homing of BMSCs. Results The therapeutic effect of combined EA+BMSCs on damaged tissue was the strongest among all the groups as indicated by HE and immunohistochemical staining. The expression of SDF-1 and MCP-3 was significantly increased by combined EA and BMSC treatment when compared with the other groups (P=0.01 to P<0.05), suggesting promotive effects of EA on the homing of BMSCs. Conclusion The combination of EA and BMSC transplantation effectively repaired the impaired anal sphincters. The underlying mechanism might be associated with apparent promotive effects of EA on the homing of BMSCs. Our study provides a theoretical basis for the development of a non-surgical treatment method for FI secondary to muscle impairment.


Sign in / Sign up

Export Citation Format

Share Document