Relaxin mitigates microvascular damage and inflammation following cardiac ischemia-reperfusion.

Microvascular obstruction (MVO) and leakage (MVL) forms a pivotal part of microvascular damage following cardiac ischemia-reperfusion (IR). We tested the effect of relaxin therapy on MVO and MVL in mice following cardiac IR injury including severity of MVO and MVL, opening capillaries, infarct size, regional inflammation, cardiac function and remodelling, and permeability of cultured endothelial monolayer. Compared to vehicle group, relaxin treatment (50 µg/kg) reduced no-reflow area by 38% and the content of Evans blue as a permeability tracer by 56% in jeopardized myocardium (both P < 0.05), effects associated with increased opening capillaries. Relaxin also decreased leukocyte density, gene expression of cytokines, and mitigated IR-induced decrease in protein content of VE-cadherin and relaxin receptor. Infarct size was comparable between the two groups. At 2 weeks post-IR, relaxin treatment partially preserved cardiac contractile function and limited chamber dilatation versus untreated controls by echocardiography. Endothelial cell permeability assay demonstrated that relaxin attenuated leakage induced by hypoxia-reoxygenation, H2O2, or cytokines, action that was independent of nitric oxide but associated with the preservation of VE-cadherin. In conclusion, relaxin therapy attenuates IR-induced MVO and MVL and endothelial leakage. This protection was associated with reduced regional inflammatory responses and consequently led to alleviated adverse cardiac remodeling.

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats.

AIM: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. METHODS: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17ß-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. RESULTS: Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects. CONCLUSION: ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

[The changes of cardioelectrical activity of rat with myocardial infarction receiving sarcoplasmic reticulum Ca(2+)-ATPase gene modified bone marrow stem cell transplantation by microelectrode array technology].

OBJECTIVE: Therapy effects and cardiac electrical activity comparison of bone marrow stem cells (BMSCs) transplantation and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) gene modified BMSCs transplantation after acute myocardial infarction (AMI) in rats. METHODS: Rats with AMI were divided into 4 groups (n = 30) randomly: normal group (n = 6), saline group (control group, n = 8), BMSCs transplantation group (BMSCs group, n = 8) and SERCA2a gene modified BMSCs transplantation group (BMSCs + rAd.SERCA2a group, n = 8). After 14 days, cardiac function was evaluated by echocardiography and heart electrical activity was evaluated by electrocardiogram and microelectrode array (MEA) technology. RESULTS: (1) The transduction ratio of rAd.SERCA2a to BMSCs were 80% to 90%. (2) Left ventricular ejection fraction on 14 days after therapy was significantly higher in BMSCs group and BMSCs + rAd.SERCA2a group than in control group (all P < 0.05). (3) QT duration was significantly shorter [(80.30 ± 6.53) ms vs. (105.31 ± 21.89) ms, P < 0.05] and ventricular premature beats less frequent in BMSCs + rAd. SERCA2a group than in the control group. (4) MEA results suggested that isolated heart beat was significantly slowed down and frequent ventricular arrhythmias and atrioventricular block were recorded in control group. The maximum field potential and field potential duration on infarcted myocardium area in BMSCs group and BMSCs + rAd.SERCA2a group were significantly longer than those in control group[the maximum field potential: (0.51 ± 0.15), (0.55 ± 0.16), (0.23 ± 0.10) mV; field potential duration: (104.5 ± 25.43), (107.67 ± 24.01), (63.00 ± 20.34) ms; all P < 0.05]. (5) The conduction time was the shortest and the cardiac electrical conduction consistency in myocardial infarction tissue was significantly improved in BMSCs + rAd.SERCA2a group. CONCLUSIONS: BMSCs and SERCA2a gene modified BMSCs transplantation could significantly improve cardiac function and BMSCs + rAd.SERCA2a could also effectively improve electrical conduction of infarcted myocardium and attenuate the incidence of arrhythmia after myocardial infarction in rats.