Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Department of Biological Sciences, Faculty of Science, University of Cape Town, Cape Town, South Africa.
Microcirculation. 2020 Jul;27(5):e12612. doi: 10.1111/micc.12612. Epub 2020 Feb 25.
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.
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).
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.
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.
鞘氨醇-1-磷酸是一种天然代谢产物，具有心脏保护作用，但它对缺血再灌注期间内皮糖萼损伤的影响尚不清楚。因此，我们研究了鞘氨醇-1-磷酸在缺血再灌注期间对内皮糖萼的影响。
用 Krebs-Henseleit 缓冲液在 Langendorff 系统上灌注 Wistar 大鼠分离的心脏，并在缺血再灌注前用鞘氨醇-1-磷酸（10 nmol/L）预处理。用三苯基四唑氯化物染色法测量梗死面积（每组 n≥6）。通过计算总水含量（每组 n=7）和组织学定量间质腔（每组 n≥3）评估心脏水肿。使用 ELISA 定量缺血后释放的 syndecan-1。在灌注固定的心脏中评估 syndecan-1 免疫染色强度（每组 n≥3）。
缺血再灌注前用鞘氨醇-1-磷酸预处理可减少缺血再灌注后分离心脏的梗死面积（P=0.01 与缺血再灌注相比）。然而，鞘氨醇-1-磷酸对冠状流出物中的 syndecan-1 水平或心脏组织中 syndecan-1 免疫染色信号强度没有影响。对照组和缺血组的心脏总水含量无显著差异，但单独用鞘氨醇-1-磷酸处理的心脏总水含量明显降低。
这些结果表明，鞘氨醇-1-磷酸诱导的缺血再灌注损伤的心脏保护作用不是通过维持内皮糖萼中的 syndecan-1 介导的。
