Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats
Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats
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DOI：
10.1159/000452575
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发表时间：
2016-11
影响因子：
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通讯作者：
Qing Zhao;J. Yin;Zeyuan Lu;Yiwei Kong;Guangyuan Zhang;Bing-hui Zhao;Feng Wang
中科院分区：
文献类型：
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作者：
Qing Zhao;J. Yin;Zeyuan Lu;Yiwei Kong;Guangyuan Zhang;Bing-hui Zhao;Feng Wang
背景：舒洛地特是一种强效的抗凝血酶药物，具有保护肾功能。然而，它是否对造影剂肾病（CIN）有有益作用仍然是未知的。在本研究中，我们评估了舒洛地特对CIN的治疗效果，并探讨了可能的机制。方法：先静脉注射吲哚美辛，再静脉注射异维醇和L-NAME建立CIN模型。将sd - dawley大鼠分为4组：对照组、CIN组、CIN+载药组（载药预处理CIN大鼠）和CIN+舒洛地特（舒洛地特预处理CIN大鼠）。在诱导CIN前30分钟静脉给予舒洛地特或同等体积的载体。所有动物于CIN后24h处死，取肾组织，评估肾损伤、肾氧化应激和细胞凋亡水平。同时测定血浆抗凝血酶III （ATIII）活性。结果：与CIN未治疗组相比，舒洛地特注射液改善了CIN大鼠的肾功能，减轻了肾小管损伤，降低了氧化应激和细胞凋亡水平。此外，我们还发现舒洛地特给药组ATIII活性明显高于车注CIN大鼠。在体外研究中，HK2细胞暴露于Ioversol，并确定Sulodexide的细胞保护作用。Sulodexide预处理通过抑制caspase-3活性保护HK2细胞免受Ioversol的细胞毒性。舒洛地德预孵育也能减弱h2o2诱导的ROS、凋亡和caspase-3水平的升高。结论：舒洛地特通过激活ATIII，抑制氧化应激、炎症和细胞凋亡，对CIN具有保护作用。
Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.