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)，每组各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。

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.