AIM: To investigate the repair mechanism associated with cholesterol synthesis regulated by silent information regulator 1(SIRT1)in rat model of optic nerve damage.

METHODS: Preparation of optic nerve damage in 70 rats was randomly divided into normal group(10 rats), resveratrol treatment group(experimental group 30 rats)and PBS buffer control group(30 rats). The experimental group and control group was further divided into 3 subgroups(each group 10 rats), respectively. After 7, 14, 21d injected resveratrol or PBS, optic nerve injury were observed, then the rats were sacrificed. Retina was segregated; the surviving retinal ganglion cell(RGCs)was counted. Dissection of optic nerve, cholesterol content of them were tested; RT-PCR was used to detect mRNA expression of SIRT1, SREBP2 and HMGCR; Western blot assay was used to test the protein expression levels of SIRT1, cholesterol regulatory element binding protein 2(SREBP2)and HMGCR.

RESULTS: The numbers of RGCs and cholesterol levels of rat model with optic nerve injury decreased significantly(P<0.01). The mRNA and protein expression levels of SIRT1, SREBP2 and HMGCR were all decreased in a time-dependent manner(P<0.05). Three components of the three time points, with time injuries were aggravated, and the extent of damage was significantly reduced in the treatment group compared with the control group. But in resveratrol treatment group, the cholesterol levels and mRNA or protein expression of SIRT1, SREBP2, HMGCR in optic nerve were significantly restored in a time-dependent(P<0.05). The number of surviving RGCs restored significantly in resveratrol treatment group(P<0.01)in a time-dependent manner.

CONCLUSION: Up-regulating the expression of SIRT1, SREBP2 and down-regulating HMGCR by resveratrol could repair the injury of optic nerve through promoting the synthesis of cholesterol in neurons and retinal ganglion cells in the repair process. SIRT1 may be as a promising new target for treatment on optic nerve damage.