大黄酚对青光眼神经退行性病变的保护作用及其信号转导通路

Protective effect of chrysophanol on neural degeneration caused by glaucoma and its mechanism

目的:探讨大黄酚对慢性青光眼大鼠的保护作用及其作用机制。方法:采用双极电凝器电凝巩膜表面3组静脉,建立慢性高眼压大鼠模型,分为3组。一组为高眼压模型组,一组为大黄酚低剂量组(25mg/kg),一组为大黄酚高剂量组(50mg/kg),每组备15只,右眼为实验眼,左眼为正常对照眼。连续给药6wk,后处死大鼠并摘取眼球,PCR和Western-blot检测PERK和ROCK-1在视网膜中的表达。结果:大黄酚高、低剂量组能有效降低大鼠眼内压,与模型眼相比有显著统计学差异(P<0.01)。正常对照视网膜p-PERK蛋白水平表达比较低,青光眼模型组表达显著升高,高、低剂量大黄酚使其表达增高。ROCK-1在视网膜中的表达在青光眼模型组表达最高,各治疗组均可使其表达下降,以高剂量组下降最显著。RT-PCR结果表明,高剂量组大鼠视网膜PERK mRNA水平明显高于模型对照眼;ROCK-1 mRNA水平则显著降低。结论:高剂量大黄酚能有效降低青光眼大鼠的眼内压,其作用机制可能是通过激活PERK蛋白磷酸化以调控PERK/ROCK信号转导而发挥其保护作用。

AIM：To investigate the effect and mechanism of chrysophanol for rat model with glaucoma. METHODS：The glaucoma rat models were made by cauterization of three episcleral veins. Then the glaucoma rats were divided into three groups. Group 1 was the untreated intraocular hypertension group. Group 2 was the low dose of chrysophanol group（25mg/kg）. Group 3 was the high dose of chrysophanol group（50mg/kg）, 15 rats in each group. The right eyes were the experiment eyes while the left were the control ones. After 6wk treatment, the mRNA and protein of protein kinase-like endoplasmic reticulum kinase（PERK）and Rho kinase 1（ROCK-1）were determined in the retina. RESULTS：The chrysophanol reduced intraocular pressure（IOP）of experiment eyes, which was significantly lower than that of control eyes（P〈0.01）. Compared with the normal group, the p-PERK protein increased significantly in the retina of glaucoma model group and chrysophanol increased the lever of p-PERK protein. The ROCK-1 protein level increased significantly in glaucoma group, it all decreased in these treatment groups, and it decreased significantly in high dose treatment group. Detected by TR-PCR, chrysophanol also could activate the mRNA of PERK and inhibited the mRNA expression of ROCK-1 in a rat model of glaucoma.CONCLUSION：These results suggest that chrysophanol can reduce the IOP through the phosphorylation of PERK protein to regulate the PERK/ROCK signaling in glaucoma rat model.