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血管紧张素II 1型受体阻滞剂和血管紧张素转换酶抑制剂对链脲佐菌素诱导的糖尿病大鼠眼内生长因子及其受体的影响。

Effect of angiotensin II type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats.

作者信息

Byon Ik Soo, Lee Dong Hyun, Jun Eun Sook, Shin Min Kyu, Park Sung Who, Lee Ji Eun

机构信息

Department of Ophthalmology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Korea.

College of Medicine, Pusan National University, Yangsan 50612, Korea.

出版信息

Int J Ophthalmol. 2017 Jun 18;10(6):896-901. doi: 10.18240/ijo.2017.06.10. eCollection 2017.

Abstract

AIM

To investigate the effect of angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats.

METHODS

Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM), candesartan-treated DM, and enalapril-treated DM (each group, =10). After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg·d)] and enalapril [ACEI, 10 mg/(kg·d)] were administered to rats orally for 4wk. Vascular endothelial growth factor (VEGF) and angiotensin II (Ang II) concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor (AT1R) levels were assessed at week 4 by Western blotting.

RESULTS

Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control (=0.04 and 0.005, respectively). Vitreous AT1R increased significantly in DM compared to the other three groups (<0.007). Candesartan-treated DM rats showed higher vitreal AT1R concentration than the enalapril-treated DM group and control (<0.001 and =0.005, respectively). No difference in vitreous Ang II and AT1R concentration was found between the enalapril-treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups.

CONCLUSION

Increased Ang II and AT1R in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

摘要

目的

研究1型血管紧张素II受体阻滞剂(ARB)和血管紧张素转换酶抑制剂(ACEI)对链脲佐菌素诱导的糖尿病大鼠眼内生长因子及其受体的影响。

方法

将40只Sprague-Dawley大鼠分为4组:对照组、糖尿病(DM)组、坎地沙坦治疗的DM组和依那普利治疗的DM组(每组n = 10)。通过链脲佐菌素诱导DM后,给大鼠口服坎地沙坦[ARB,5 mg/(kg·d)]和依那普利[ACEI,10 mg/(kg·d)],持续4周。采用酶联免疫吸附测定法测量玻璃体内血管内皮生长因子(VEGF)和血管紧张素II(Ang II)浓度,并在第4周通过蛋白质免疫印迹法评估VEGF受体2和1型血管紧张素II受体(AT1R)水平。

结果

DM组和坎地沙坦治疗的DM组玻璃体内Ang II水平显著高于对照组(分别为P = 0.04和0.005)。与其他三组相比,DM组玻璃体内AT1R显著增加(P < 0.007)。坎地沙坦治疗的DM大鼠玻璃体内AT1R浓度高于依那普利治疗的DM组和对照组(分别为P < 0.001和P = 0.005)。依那普利治疗的DM组与对照组之间玻璃体内Ang II和AT1R浓度无差异。所有4组中VEGF及其受体均低于最低检测限。

结论

高血糖状态下Ang II和AT1R增加表明眼内肾素-血管紧张素系统被激活,全身性ACEI比全身性ARB更有效地抑制该系统。

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