姜黄素对慢性高眼压大鼠视网膜神经节细胞凋亡的影响及机制

Effects and mechanisms of curcumin on apoptosis of retinal ganglion cells in chronic ocular hypertension rats

摘要:

目的：探讨姜黄素对慢性高眼压大鼠视网膜神经节细胞(RGCs)凋亡的影响及机制。

方法：将21只SD大鼠随机分为3组，每组7只，高眼压模型组和姜黄素治疗组大鼠通过烧灼巩膜上静脉法建立慢性高眼压模型，假手术组大鼠仅剪开球结膜，不烧灼巩膜上静脉； 姜黄素治疗组给予4mL/kg姜黄素灌胃，假手术组和高眼压模型组给予4mL/kg纯水灌胃，连续3wk。造模后3wk，采用HE染色观察各组大鼠视网膜组织形态病理变化、RGCs数量及神经节细胞层(GCL)厚度； 采用TUNEL染色观察各组大鼠RGCs和视网膜细胞凋亡情况； 采用实时荧光定量PCR、免疫组织化学染色和Western blot法检测各组大鼠视网膜谷氨酰半胱氨酸连接酶调节亚基(GCLM)与血红素加氧酶-1(HO-1)的表达水平。

结果：与假手术组相比，高眼压模型组和姜黄素治疗组大鼠视网膜组织形态紊乱，RGCs数量减少，GCL变薄，RGCs和视网膜细胞凋亡率均升高，GCLM和HO-1表达量均升高； 与高眼压模型组相比，姜黄素治疗组大鼠视网膜组织形态基本正常，RGCs数量增多，GCL增厚，RGCs和视网膜细胞凋亡率均降低，GCLM和HO-1表达量均升高。

结论：姜黄素在慢性高眼压大鼠模型中可通过上调抗氧化基因GCLM与HO-1的表达抑制RGCs凋亡。

Abstract:

AIM:To investigate the effects and mechanisms of curcumin on apoptosis of retinal ganglion cells(RGCs)in chronic ocular hypertension rats.

METHODS:A total of 21 Spraque-Dawley(SD)rats were randomly divided into 3 groups with 7 rats in each group. The rat models of chronic ocular hypertension were established by cauterization of the superior scleral veins in the high intraocular pressure model group and the curcumin treatment group, and the sham operation group only cut the conjunctiva without the cauterization of the superior scleral veins; the rats in the curcumin treatment group were intragastrically treated with curcumin at a dose of 4mL/kg, and the rats in the sham operation group and the high intraocular pressure model group were treated with pure water at a dose of 4mL/kg for 3wk. After 3wk, HE staining was used to observe the morphological and pathological changes of retina, the number of RGCs and the thickness of ganglion cell layer(GCL)in each group of rats; TUNEL staining was used to observe the apoptosis of RGCs and retinal cells in each group of rats; the expression levels of glutamate-cysteine ligase modifier subunit(GCLM)and heme oxygenase-1(HO-1)in the retina of each group of rats were detected by real-time fluorescence quantitative PCR, immunohistochemical staining and Western blot.

RESULTS:Compared with the sham operation group, the retinal morphology of rats in the high intraocular pressure model group and the curcumin treatment group was disorganized, the number of RGCs was reduced, the GCL was thinner, the apoptosis rate of RGCs and retinal cells increased, and the expression levels of GCLM and HO-1 increased. Compared with the high intraocular pressure model group, the retinal morphology of rats in the curcumin treatment group was basically normal, the number of RGCs increased, the GCL thickened, the apoptosis rate of RGCs and retinal cells decreased, and the expression levels of GCLM and HO-1 increased.

CONCLUSION:Curcumin can inhibit the apoptosis of RGCs in the rat model of chronic ocular hypertension by up-regulating the expression of antioxidant genes GCLM and HO-1.