整合素连接激酶抑制可减轻链脲佐菌素诱导的糖尿病大鼠视网膜通透性。

Integrin-linked kinase inhibition attenuates permeability of the streptozotocin-induced diabetic rat retina.

机构信息

Department of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University of PLA, Xian, People's Republic of China,

出版信息

Cell Biochem Biophys. 2013;67(3):1467-72. doi: 10.1007/s12013-013-9647-z.

DOI:10.1007/s12013-013-9647-z

PMID:23712867

Abstract

Integrin-linked kinase (ILK), as a multi-functional regulator, has been associated with diabetic retinopathy (DR). In this study, we investigated whether inhibition of ILK could result in therapeutic effects. Diabetes mellitus's rats were induced by streptozotocin (STZ) injection. After 1 weeks induction, rats were injected intraperitoneally daily with ILK inhibitor, QLT0267, at 5 mg/kg. Then, the rats were examined by 4, 8, and 12 weeks after first STZ injection. We found that QLT0267 treatment could not only lower ILK level in retina at as early as 3 weeks after the onset of diabetes but also attenuate retina permeability, which was measured by Evan's blue. Maximum effect was found in 11 weeks treatment. Meanwhile, QLT0267 did not disturbed blood glucose concentration. Furthermore, QLT0267 inhibited Akt (Ser473) activation and reduced expression of HIF1α and VEGF which were evaluated by western blot, real time PCR, and immunohistochemistry. We conclude that ILK may be a new target for DR.

摘要

整合素连接激酶（ILK）作为一种多功能调节剂，与糖尿病视网膜病变（DR）有关。在这项研究中，我们研究了抑制 ILK 是否可以产生治疗效果。通过链脲佐菌素（STZ）注射诱导糖尿病大鼠。诱导 1 周后，大鼠每天经腹腔注射 ILK 抑制剂 QLT0267，剂量为 5mg/kg。然后，在首次 STZ 注射后 4、8 和 12 周对大鼠进行检查。我们发现，QLT0267 治疗不仅可以在糖尿病发病后 3 周内降低视网膜中的 ILK 水平，还可以减轻视网膜通透性，这可以通过 Evans 蓝测定。在 11 周的治疗中，效果达到最大。同时，QLT0267 并未干扰血糖浓度。此外，通过 Western blot、实时 PCR 和免疫组织化学评估，QLT0267 抑制 Akt（Ser473）激活并降低 HIF1α 和 VEGF 的表达。我们得出结论，ILK 可能是 DR 的一个新靶点。