CAJ | 학술논문

目的：探讨沉默信息调节因子1( silent information regulator 1, SIRT1)调控胆固醇合成在视神经损伤修复中的作用机制。 　　方法：制备视神经损伤的大鼠模型,随机数字法将70只大鼠分为正常组10只,白黎芦醇治疗组(实验组)30只和PBS缓冲液对照组(对照组)30只；再将实验组和对照组分别分为三组,每组各10只；将白黎芦醇或PBS分别注射实验组和对照组大鼠,观察视神经损伤后第7,14,21 d处死大鼠。分离视网膜,观察各组大鼠视网膜神经节细胞( retinal ganglion cell ,RGCs)的存活数量。分离术眼视神经,检测其胆固醇含量；RT-PCR法检测SIRT1、SREBP2和HMGCR的mRNA表达水平；Western blot法检测SIRT1、SREBP2和HMGCR蛋白表达水平。 　　结果：损伤模型大鼠的视网膜RGCs的存活数量以及视神经胆固醇含量均明显减少( P<0.01)；SIRT1、SREBP2和HMGCR的mRNA和蛋白表达水平均下降( P<0.05),并呈时间依赖关系。三组分三个时间点,随时间延长损伤均加重,而治疗组损伤程度较对照组明显减弱。而白黎芦醇治疗组的视神经胆固醇含量以及SIRT1、SREBP2、HMGCR的mRNA和蛋白表达水平,RGCs存活数量均明显回升(P<0.01),且呈时间依赖关系。 　　结论：白黎芦醇通过上调SIRT1、SREBP-2及其下游调控基因HMGCR的表达,从而进一步促进神经元细胞的胆固醇合成以及视网膜神经节细胞的损伤后修复过程。
목적：탐토침묵신식조절인자1( silent information regulator 1, SIRT1)조공담고순합성재시신경손상수복중적작용궤제。 　　방법：제비시신경손상적대서모형,수궤수자법장70지대서분위정상조10지,백려호순치료조(실험조)30지화PBS완충액대조조(대조조)30지；재장실험조화대조조분별분위삼조,매조각10지；장백려호순혹PBS분별주사실험조화대조조대서,관찰시신경손상후제7,14,21 d처사대서。분리시망막,관찰각조대서시망막신경절세포( retinal ganglion cell ,RGCs)적존활수량。분리술안시신경,검측기담고순함량；RT-PCR법검측SIRT1、SREBP2화HMGCR적mRNA표체수평；Western blot법검측SIRT1、SREBP2화HMGCR단백표체수평。 　　결과：손상모형대서적시망막RGCs적존활수량이급시신경담고순함량균명현감소( P<0.01)；SIRT1、SREBP2화HMGCR적mRNA화단백표체수평균하강( P<0.05),병정시간의뢰관계。삼조분삼개시간점,수시간연장손상균가중,이치료조손상정도교대조조명현감약。이백려호순치료조적시신경담고순함량이급SIRT1、SREBP2、HMGCR적mRNA화단백표체수평,RGCs존활수량균명현회승(P<0.01),차정시간의뢰관계。 　　결론：백려호순통과상조SIRT1、SREBP-2급기하유조공기인HMGCR적표체,종이진일보촉진신경원세포적담고순합성이급시망막신경절세포적손상후수복과정。
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.