CAJ | 학술논문

目的：初步探讨山茱萸多糖治疗年龄相关性白内障的可能机制，为其预防和治疗寻找新的药物和靶点。方法：选用60只昆明大鼠，按体质量随机分为3组，每组20只，分别为对照组（C组）、衰老模型组（A组）和山茱萸多糖给药组（D组）。在相同环境下，C组正常饮食，每日颈背部皮下注射0?9％氯化钠注射液，剂量计算参照其他给药组D-半乳糖给药量；A和D组正常饮食，每日颈背部皮下注射D-半乳糖100 mg/（ kg·d）；连续皮下注射45 d后，C和A组每日按照等剂量灌药量灌服温开水；D组按照多糖0?4 g/kg灌服山茱萸多糖，连续灌服30 d。试验终期颈椎离断术处死大鼠，4℃迅速取眼分离晶状体置于液氮备用。免疫组化方法检测各组间总超氧化物歧化酶（ T-SOD）和总抗氧化能力（ T-AOC）的变化，RT-PCR（逆转录cDNA的聚合酶链式扩增反应）检测各组Sirt1、p53和FOXO1 mRNA的表达变化。结果：A组和D组大鼠晶状体中 Sirt1 mRNA的表达较 C组均显著上升（ P＜0?05、P＜0?01），且D组较A组显著上升（P＜0?01）；A组和D组大鼠晶状体中p53 mRNA的表达较C组显著上升（P均＜0?01），而D组较A组显著下降（P＜0?05）；A组和D组大鼠晶状体中FOXO1 mRNA的表达较C组显著上升（P＜0?05、P＜0?01），且D组较A组显著上升（P＜0?01）。另外A组和D组大鼠晶状体中T-SOD的活性较C组显著上升（P均＜0?01），且D组较A组显著上升（P＜0?01）；A组和D组大晶状体中鼠T-AOC的活性较C组显著上升（P均＜0?01），且D较A组显著上升（P＜0?01）。结论：山茱萸多糖可能通过调节Sirt1的表达，从而调节下游基因p53和FOXO1的表达，最终抑制或延缓晶状体上皮细胞的凋亡，减缓年龄相关性白内障的进展。
목적：초보탐토산수유다당치료년령상관성백내장적가능궤제，위기예방화치료심조신적약물화파점。방법：선용60지곤명대서，안체질량수궤분위3조，매조20지，분별위대조조（C조）、쇠로모형조（A조）화산수유다당급약조（D조）。재상동배경하，C조정상음식，매일경배부피하주사0?9％록화납주사액，제량계산삼조기타급약조D-반유당급약량；A화D조정상음식，매일경배부피하주사D-반유당100 mg/（ kg·d）；련속피하주사45 d후，C화A조매일안조등제량관약량관복온개수；D조안조다당0?4 g/kg관복산수유다당，련속관복30 d。시험종기경추리단술처사대서，4℃신속취안분리정상체치우액담비용。면역조화방법검측각조간총초양화물기화매（ T-SOD）화총항양화능력（ T-AOC）적변화，RT-PCR（역전록cDNA적취합매련식확증반응）검측각조Sirt1、p53화FOXO1 mRNA적표체변화。결과：A조화D조대서정상체중 Sirt1 mRNA적표체교 C조균현저상승（ P＜0?05、P＜0?01），차D조교A조현저상승（P＜0?01）；A조화D조대서정상체중p53 mRNA적표체교C조현저상승（P균＜0?01），이D조교A조현저하강（P＜0?05）；A조화D조대서정상체중FOXO1 mRNA적표체교C조현저상승（P＜0?05、P＜0?01），차D조교A조현저상승（P＜0?01）。령외A조화D조대서정상체중T-SOD적활성교C조현저상승（P균＜0?01），차D조교A조현저상승（P＜0?01）；A조화D조대정상체중서T-AOC적활성교C조현저상승（P균＜0?01），차D교A조현저상승（P＜0?01）。결론：산수유다당가능통과조절Sirt1적표체，종이조절하유기인p53화FOXO1적표체，최종억제혹연완정상체상피세포적조망，감완년령상관성백내장적진전。
OBJECTIVE:To discuss the possible mechanism of the dogwood polysaccharide for treatment of age-related cataract in an attempt to find new drugs and target points for its prevention and treatment. METHODS:60 Kunming mice were enrolled in our study and divided into 3 groups of 20 each:Control group( C) , the aging model group(A) and dogwood polysaccharide administration group(D). In the same environment,Group C were fed with normal diet and subcutaneously injected with 0?9% Sodium Chloride Injection in the nape daily as per the dosage of D-galactose in the other administration group; Group A and D were also fed with normal diet and subcutaneously injected with D-galactose 100 mg/( kg·d ) in the nape daily; after subcutaneous injection for 45 consecutive days, Group C and Group A were fed with warm water at the same dose of drug administration; Group D was fed with dogwood polysaccharide at a dose of 0?4 g/kg for polysaccharide for 30 consecutive days. At last all mice were killed by cervical dislocation, with eye lens extracted quickly at 4 ℃ and stored in liquid nitrogen for use. T-SOD and T-AOC were detected by immunohistochemical methods, and Sirt1, p53 and FOXO1 mRNA expressions were detected by RT-PCR. RESULTS:Sirt1 mRNA in disease group and the treatment group increased significantly compared with the control group(P<0?05, P<0?01), and Sirt1 mRNA in the treatment group increased significantly compared with the disease group(P<0?01); p53 mRNA in disease group and the treatment group increased significantly compared with the control group(P<0?01, P<0?01), but p53 mRNA in the treatment group decreased significantly compared with the disease group( P <0?05 ); FOXO1 mRNA in disease group and the treatment group increased significantly compared with the control group ( P <0?05 , P <0?01 ) , and FOXO1 mRNA in the treatment group increased significantly compared with the disease group(P<0?05). Furthermore, T-SOD and T-AOC in the disease group and the treatment group increased significantly compared with the control group ( P <0?01 , P <0?01 ) , and SOD and T-AOC in the treatment group increased significantly compared with the disease group ( P <0?01 , P <0?01 ) . CONCLUSIONS:Dogwood polysaccharide may regulate the expression of downstream genes p53 and FOXO1 possibly by regulating the expression of Sirt1 , ultimately inhibiting or delaying the apoptosis of epithelial cells in eye lens and slow the progression of age-related cataracts.