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姜黄素抑制糖尿病大鼠视网膜神经元丢失并提高钙调蛋白依赖性蛋白激酶II活性

Curcumin Inhibits Neuronal Loss in the Retina and Elevates Ca²⁺/Calmodulin-Dependent Protein Kinase II Activity in Diabetic Rats.

作者信息

Li Jun, Wang Peipei, Zhu Yanxia, Chen Zhen, Shi Tianyan, Lei Wensheng, Yu Songping

机构信息

Department of Ophthalmology, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical University , Lishui, Zhejiang Province, People's Republic of China .

出版信息

J Ocul Pharmacol Ther. 2015 Nov;31(9):555-62. doi: 10.1089/jop.2015.0006. Epub 2015 Jul 24.

Abstract

PURPOSE

To determine whether curcumin offers neuroprotection to minimize the apoptosis of neural cells in the retina of diabetic rats.

METHODS

Streptozotocin (STZ)-induced diabetic rats and control rats were used in this study. A subgroup of STZ-induced diabetic rats were treated with curcumin for 12 weeks. Retinal histology, apoptosis of neural cells in the retina, electroretinograms, and retinal glutamate content were evaluated after 12 weeks. Retinal levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p-CaMKII), and cleaved caspase-3 were determined by Western blot analysis.

RESULTS

The amplitudes a-wave, b-wave, and oscillatory potential were reduced by diabetes, but curcumin treatment suppressed this reduction of amplitudes. Curcumin also prevented cell loss from the outer nuclear, inner nuclear, and ganglion cell layers. Apoptosis of retinal neurons was detected in diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats, but was significantly reduced in the curcumin-treated group. Furthermore, p-CaMKII and cleaved caspase-3 expression were upregulated in the diabetic retina, but reduced in curcumin-treated rats.

CONCLUSIONS

Curcumin attenuated diabetes-induced apoptosis in retinal neurons by reducing the glutamate level and downregulating CaMKII. Thus, curcumin might be used to prevent neuronal damage in the retina of patients with diabetes mellitus.

摘要

目的

确定姜黄素是否能提供神经保护作用,以减少糖尿病大鼠视网膜神经细胞的凋亡。

方法

本研究使用链脲佐菌素(STZ)诱导的糖尿病大鼠和对照大鼠。将STZ诱导的糖尿病大鼠亚组用姜黄素治疗12周。12周后评估视网膜组织学、视网膜神经细胞凋亡、视网膜电图和视网膜谷氨酸含量。通过蛋白质印迹分析测定视网膜中钙/钙调蛋白依赖性蛋白激酶II(CaMKII)、磷酸化CaMKII(p-CaMKII)和裂解的半胱天冬酶-3的水平。

结果

糖尿病使a波、b波和振荡电位的振幅降低,但姜黄素治疗可抑制这种振幅降低。姜黄素还可防止外核层、内核层和神经节细胞层的细胞丢失。在糖尿病大鼠中检测到视网膜神经元凋亡。糖尿病大鼠视网膜中谷氨酸浓度较高,但在姜黄素治疗组中显著降低。此外,p-CaMKII和裂解的半胱天冬酶-3表达在糖尿病视网膜中上调,但在姜黄素治疗的大鼠中降低。

结论

姜黄素通过降低谷氨酸水平和下调CaMKII减轻糖尿病诱导的视网膜神经元凋亡。因此,姜黄素可能用于预防糖尿病患者视网膜的神经元损伤。

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