| Objective Endothelial-interstitialtransformation(endothelial-to-mesenchymal transition,End MT)plays an important role in myocardial fibrosis,End MT not only considered ectomesenchymal cells leading to endothelial cells into the main drive process,but alsoplays crucial physiological and pathophysiological roles in the development and structural remodel of cardiac muscle,which can be actived by inflammation factors,lack of oxygen,sugar and other stimulus.Ghrelin was first identified and characterized from rat stomach in 1999.It is proved that ghrelin plays important roles for the controlling appetite,maintaining weight,regulating cell proliferation,glucose and fat metabolism and apoptosis and gastrointestinal,cardiovascular,immune function.In recent years,more and more studies have found that Ghrelin can inhibit coronary inflammation,protecting endothelial function,expansion of coronary artery,resisting sympathetic nervous excitement,andimproving the cardiac insufficiencyin patients with heart failure.However,whether Ghrelincan improve the myocardial fibrosis by regulating End MT has not been investigated.In this study,we established the rat model of myocardial fibrosisafter coronary artery ligation,and observe the effect of Ghrelin treatment on myocardial fibrosis and End MT after myocardial infarction in rats.Methods In this study,60 male rats were randomly divided into corncary artery ligation group(n=45)and sham operation group(n=15).They received coronary artery ligation or sham operation respectively.after that the coronary artery ligation group further divided in control group,Ghrelinlow dose treatment group and Ghrelin high dose treatment group.The sham operation group and control group recieved intraperitoneal injection of saline(0.02mg/kg·d),while the Ghrelinlow dose treatment group and Ghrelin high dose treatment group were given Ghrelin solution(0.02mg/kg·d,0.2mg/kg·d)by intraperitoneal injection.The rats were sacrificed after 4 weeks of drug treatment and normal feeding.The rat and its left ventricular weight were measured.The degree of myocardial fibrosis was observed by HE and Masson staining.The expression of End MT markers ?-SMA and CD-31 expression were observed using immunofluorescence method.The expression of ?-SMA,CD31,VE-cadherin and FSP-1 in myocardium were detected by Western-Blot assay.Results In the isolated heart of the rat,we found that the weight,heart / body weight ratio of the control group was significantly higher than that of the sham operation group,while the weight and heart / body weight ratio of Ghrelin high and low dose group were lower than those of the control group.HE and masson staining showed that the collagen fibers in the controlgroup were significantly higher than those in the sham operation group,and the collagen fibers in Ghrelin high and low dose groups were significantly decreased.Immunofluorescence showed that CD31 and ?-SMA were positive for CD31,and CD31 expression was up-regulated by Ghrelin and down-regulated ?-SMA.Western-Blot showed that the expression of ?-SMA and FSP-1 protein in Ghrelin high and low treatment group was significantly lower than that in control group,and the expression of CD31 and VE-cadherin was significantly higher than that of control group.Conclusion Ghrelin inhibits End MT after MI in rats,thereby improving myocardial fibrosis. |
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