The effect of sphingosine-1-phosphate on the endothelial glycocalyx during ischemia-reperfusion injury in the isolated rat heart
The effect of sphingosine-1-phosphate on the endothelial glycocalyx during ischemia-reperfusion injury in the isolated rat heart
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DOI：
10.1111/micc.12612
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发表时间：
2020-02-25
期刊：
影响因子：
2.4
通讯作者：
Kelly-Laubscher, Roisin
中科院分区：
文献类型：
--
作者：
Araibi, Hala;van der Merwe, Elizabeth;Kelly-Laubscher, Roisin
目的1-磷酸鞘氨醇是一种具有心脏保护作用的天然代谢物，但其对缺血再灌流时内皮细胞糖基化损伤的影响尚不清楚。因此，我们研究了1-磷酸鞘氨醇在缺血再灌流过程中对血管内皮细胞功能的影响。方法大鼠离体心在含Krebs-Henseleit缓冲液的朗宁多夫系统中灌流，在缺血再灌流前用1-磷酸鞘氨醇(10nmol/L)进行预处理。用氯化三苯基四氮唑染色(n>；=每组6只)测量脑梗塞面积。通过计算总含水量(n=7)和组织学定量间质间隙(n>；=3)来评估心脏水肿。用双抗体夹心法测定缺血后冠脉释放Syndecan-1的量。结果1-磷酸鞘氨醇预处理可缩小缺血-再灌流心肌梗死面积(P=.01 vs缺血-再灌流)。然而，鞘氨醇-1-磷酸对冠脉流出物中Syndecan-1的水平或心脏组织中Syndecan-1免疫染色信号的强度没有影响。心肌总含水量在对照组和缺血组之间无明显差异，但单用1-磷酸鞘氨醇后心脏总含水量显著降低。结论1-磷酸鞘氨醇对缺血再灌注损伤的保护作用不是通过维持内皮细胞膜上Syndecan-1的表达来实现的。
Objective Sphingosine-1-phosphate is a natural metabolite that is cardioprotective, but its effects on endothelial glycocalyx damage during ischemia-reperfusion are unknown. Therefore, we investigated the effect of sphingosine-1-phosphate on the endothelial glycocalyx during ischemia-reperfusion.Methods Isolated hearts from Wistar rats were perfused on a Langendorff system with Krebs-Henseleit buffer and pretreated with sphingosine-1-phosphate (10 nmol/L) before ischemia-reperfusion. Infarct size was measured by triphenyl tetrazolium chloride staining (n >= 6 per group). Cardiac edema was assessed by calculating total water content (n = 7 per group) and histologically quantifying the interstitial compartment (n >= 3 per group). The post-ischemic coronary release of syndecan-1 was quantified using ELISA. Syndecan-1 immunostaining intensity was assessed in perfusion-fixed hearts (n >= 3 per group).Results Pretreatment with sphingosine-1-phosphate decreased infarct size in isolated hearts subjected to ischemia-reperfusion (P = .01 vs ischemia-reperfusion). However, sphingosine-1-phosphate had no effect on syndecan-1 levels in the coronary effluent or on the intensity of the syndecan-1 immunostaining signal in cardiac tissue. Heart total water content was not significantly different between control and ischemic groups but was significantly decreased in hearts treated with sphingosine-1-phosphate alone.Conclusion These results suggest that sphingosine-1-phosphate-induced cardioprotection against ischemia-reperfusion injury is not mediated by the maintenance of syndecan-1 in the endothelial glycocalyx.