摘要
目的 探讨双丹明目胶囊对糖尿病视网膜病变(DR)大鼠视网膜的保护作用及其机制。方法 取SPF级雄性SD大鼠40只,将大鼠随机分为8组:正常组、模型组、对照组、高剂量组、中剂量组、低剂量组、抑制剂组和激动剂组,每组5只。正常组大鼠用普通饲料喂养,其余大鼠采用高脂乳剂连续灌胃2周建立DR模型。正常组和模型组大鼠给予生理盐水(10 mL·kg^(-1))灌胃,对照组大鼠给予羟苯磺酸钙胶囊(等效给药浓度为5.8 mg·kg^(-1))灌胃,高、中、低剂量组大鼠给予不同剂量(22.4 g·kg^(-1)、11.2 g·kg^(-1)、5.6 g·kg^(-1))的双丹明目胶囊灌胃,分别相当于临床等效剂量的2.0倍、1.0倍、0.5倍,抑制剂组大鼠给予Sirtinol(10 mg·kg^(-1))、激动剂组大鼠给予SRT1720(50 mg·kg^(-1))腹腔注射。各组大鼠每天给药1次,连续12周。免疫组织化学法观察各组大鼠视网膜组织结构及STAT1、 Bim表达情况,ELISA实验和Western blot实验检测各组大鼠视网膜组织中STAT1、Bim蛋白含量和相对表达量。结果 免疫组织化学法染色显示:正常组、高剂量组和抑制剂组大鼠视网膜组织层次结构较清晰,STAT1、Bim表达呈弱阳性,着染呈浅黄色;模型组大鼠视网膜组织层次结构欠清晰,STAT1、Bim表达呈强阳性,着染呈深棕黄色。与模型组相比,正常组、对照组、高剂量组、中剂量组、低剂量组、抑制剂组、激动剂组大鼠视网膜组织中STAT1、Bim蛋白含量均显著下降(均为P<0.05)。激动剂组大鼠视网膜组织中STAT1、Bim蛋白含量均较高剂量组升高(均为P<0.05)。与模型组相比,正常组、对照组、高剂量组、中剂量组、低剂量组、抑制剂组大鼠视网膜组织中STAT1、Bim蛋白相对表达量均下降(均为P<0.05);与高剂量组相比,激动剂组大鼠视网膜组织中STAT1和Bim蛋白相对表达量均升高(均为P<0.05)。结论 双丹明目胶囊通过降低视网膜组织中STAT1和Bim相对表达量达到保护视网膜的目的。
Objective To investigate the protective effect and mechanism of Shuangdan Mingmu Capsules on the retina of diabetic retinopathy(DR)rats.Methods Totally 40 specific-pathogen-free male Sprague-Dawley rats were included and randomly divided into 8 groups:normal group,model group,control group,high-dose group,medium-dose group,low-dose group,inhibitor group and agonist group,with 5 rats in each group.The rats in the normal group were fed ordinary diets,and other rats were administered high-fat emulsion intragastrically for 2 weeks to establish the DR model.The rats in the normal group and model group were given physiological saline(10 mL·kg^(-1))intragastrically,rats in the control group were given Calcium Dobesilate Capsules(equivalent dosing concentration of 5.8 mg·kg^(-1))intragastrically,and rats in the high-,medium-and low-dose groups were given different doses of Shuangdan Mingmu Capsules(22.4 g·kg^(-1),11.2 g·kg^(-1),and 5.6 g·kg^(-1)),which were 2.0,1.0 and 0.5 times of the clinically equivalent dose,respectively.Rats in the inhibitor group were given Sirtinol(10 mg·kg^(-1)),and rats in the agonist group were given SRT1720(50 mg·kg^(-1))by intraperitoneal injection.Rats in each group were administered once a day for 12 weeks.Immunohistochemistry was used to observe the structure of retinal tissues and the expressions of signal transducer and activator of transcription 1(STAT1)and Bim in each group,and enzyme-linked immunosorbent assay and Western blot were performed to detect the protein contents and relative expressions of STAT1 and Bim in the retinal tissues of rats in each group.Results Immunohistochemical staining showed that the retinal tissues had a clear hierarchical structure and the expressions of STAT1 and Bim were weakly positive(light yellow)in the normal,high-dose and inhibitor groups;the retinal tissues had an unclear hierarchical structure and the expressions of STAT1 and Bim were strongly positive(deep brownish yellow)in the model group.Compared with the model group,STAT1 and Bim protein contents in the retinal tissues of rats in the normal,control,high-dose,medium-dose,low-dose,inhibitor and agonist groups significantly decreased(all P<0.05).The levels of STAT1 and Bim protein in the retinal tissues of rats in the agonist group increased compared with those in the high-dose group(both P<0.05).Compared with the model group,the relative expressions of STAT1 and Bim protein in the retinal tissues of rats in the normal,control,high-dose,medium-dose,low-dose and inhibitor groups decreased(all P<0.05);compared with the high-dose group,the relative expressions of STAT1 and Bim protein in the retinal tissues of rats in the agonist group increased(both P<0.05).Conclusion Shuangdan Mingmu Capsules can protect the retina by reducing the relative expressions of STAT1 and Bim in retinal tissues.
作者
郑新宝
陈佳玉
杨爱萍
夏静
陈春峰
李明芳
吴陆赟
赵永旺
ZHENG Xinbao;CHEN Jiayu;YANG Aiping;XIA Jing;CHEN Chunfeng;LI Mingfang;WU Luyun;ZHAO Yongwang(Department of Ophthalmology,Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine(preparatory stage),Shanghai 201600,China;Hunan University of Traditional Chinese Medicine,Changsha 410208,Hunan Province,China)
出处
《眼科新进展》
CAS
北大核心
2023年第4期279-283,共5页
Recent Advances in Ophthalmology
基金
湖南省中药粉体与创新药物省部共建国家重点实验室培育基地开放基金资助项目(编号:0303I0301301004)
上海市松江区科技创新项目(编号:21SJKJGG112,21SJKJGG115)。
