羟苯磺酸钙对硒性白内障大鼠晶状体上皮细胞凋亡及Nrf2/HO-1信号通路的影响  

Effects of Calcium Dobesilate on the apoptosis of lens epithelial cells in selenium induced cataract rats and Nrf2/HO-1 signal pathway

作　　者：谷李影 杜刚[1] 罗丰年[1] GU Li - ying;DU Gang;L UO Feng - nian.(Department of Ophthalmology, The 161st Hospital of PLA, Wuhan Hubei 430010, China.)

机构地区：[1]中国人民解放军第一六一医院眼科,湖北武汉430010

出　　处：《临床和实验医学杂志》2018年第11期1129-1134,共6页Journal of Clinical and Experimental Medicine

摘　　要：目的研究羟苯磺酸钙对硒性白内障大鼠晶状体上皮细胞凋亡的影响并探讨其作用机制。方法采用亚硒酸钠诱导法制备硒性白内障模型大鼠,随机分为模型组、维生素C组(维生素C18 mg/kg,每日一次灌胃)、羟苯磺酸钙低剂量组(羟苯磺酸钙50 mg/kg,每日一次灌胃)、中剂量组(羟苯磺酸钙100 mg/kg,每日一次灌胃)、高剂量组(羟苯磺酸钙200 mg/kg,每日一次灌胃),对照组(不建模)及模型组给予等体积生理盐水灌胃。连续用药4周。裂隙灯检测各组大鼠晶状体混浊程度,TUNEL法检测大鼠晶状体上皮细胞凋亡情况,实时荧光定量PCR(qRT-PCR)和蛋白免疫组化(WB)检测晶状体上皮细胞中Caspase3、Bcl-2、Bax、Nrf2、Keap1、HO-1mRNA和蛋白表达情况。结果与对照组比较,模型组大鼠模型组大鼠的晶状体混浊程度显著增加,晶状体出现大量空泡、降解、萎缩等病变,晶状体上皮细胞凋亡指数显著升高,Bcl-2蛋白表达显著下降,Bax、Caspase3、Keap1、HO-1蛋白表达显著升高,Nrf2蛋白核转移水平显著增强,差异均有统计学意义(P<0.05);与模型组比较,维生素C组、羟苯磺酸钙低、中、高剂量组大鼠晶状体混浊程度均显著降低,晶状体组织病理损伤明显改善,晶状体上皮细胞凋亡指数显著下降,Bcl-2蛋白表达显著升高,Bax、Caspase3、Keap1、HO-1蛋白表达显著降低,Nrf2蛋白核转移水平显著降低,差异均有统计学意义(P<0.05),且羟苯磺酸钙的效果呈剂量依赖性。结论羟苯磺酸钙可能通过抑制Nrf2/HO-1信号通路抑制晶状体上皮细胞凋亡,发挥对硒性白内障大鼠晶状体损伤的保护作用。Objective To study the effect of Calcium Dobesilate on the apoptosis of lens epithelial cells in selenium induced cataract rats and to explore its mechanism. Methods Selenite induced cataract model rats were prepared by Sodium Selenite,and they were randomly divided into model group,vitamin C group（ 18 mg/kg）,Calcium Dobesilate low（ 50 mg/kg）,middle（ 100 mg/kg）,and high（ 200 mg/kg） dose groups,the control group and the model group were given the same volume of normal saline for gavage. After 4 weeks of continuous medication,slit lamp was used to detect the degree of lens opacity in each group,TUNEL method was used to detect the apoptosis of lens epithelial cells in rats,the expressions of Caspase3,Bcl-2,Bax,Nrf2,Keap1,HO-1 mRNA and protein in lens epithelial cells were detected by real-time fluorescence quantitative PCR（ qRT-PCR） and protein immunohistochemistry（ WB）. Results Compared with the control group,the degree of lens opacity in the rats of the model group increased significantly. There were a lot of lesions such as vacuoles,degradation and atrophy in the lens,the apoptotic index of lens epithelial cells increased significantly,the expression of Bcl-2 protein decreased significantly. The expressions of Bax,Caspase3,Keap1 and HO-1 protein increased significantly,the Nrf2 protein nuclear transfer level increased significantly,the differences were statistically significant（ P〈0. 05）. Compared with the model group,the degree of lens opacity in the rats of the low,middle and high dose Calcium Dobesilate groups decreased significantly. The histopathological damages of the lens improved obviously,the apoptotic index of lens epithelial cells decreased significantly. The expression of Bcl-2 protein increased significantly,the expressions of Bax,Caspase3,Keap1 and HO-1 protein decreased significantly. The Nrf2 protein nuclear transfer level decreased significantly,the differences were statistically significant（ P〈0. 05）. Conclusion Calcium Dobesilate may inhibit the apoptosis of

关 键 词：大鼠 硒性白内障 羟苯磺酸钙 晶状体上皮细胞 细胞凋亡 Nrf2/HO-1信号通路 

分 类 号：R776.1[医药卫生—眼科]