目的：探讨双丹明目胶囊通过抑制cGAS-STING信号通路改善糖尿病视网膜病变(DR)小鼠视网膜炎症反应的作用机制。

方法：将SPF级雄性C57BL/6J小鼠40只随机分为2组：正常组10只连续5 d腹腔注射等体积柠檬酸钠缓充液； 模型组30只，连续5 d腹腔注射STZ(50 mg/kg)诱导建立DR小鼠模型，所有小鼠均建模成功后再随机分为模型组(使用等体积生理盐水灌胃)、双丹明目胶囊组(使用临床等效剂量11.2 g/kg双丹明目胶囊溶液灌胃)、阳性药物组(使用11.6 mg/kg羟苯磺酸钙溶液灌胃)，每组10只； 正常组10只小鼠使用等体积生理盐水灌胃。各组小鼠每日灌胃1次，干预治疗8 wk后，通过伊文思蓝染色检测各组小鼠视网膜渗漏情况，HE染色检测小鼠视网膜组织结构变化，TUNEL染色检测视网膜凋亡水平，免疫荧光检测视网膜视紫红质(Rhodopsin)、视蛋白(Opsin)、Iba1及GFAP表达水平，Western blot检测小鼠视网膜cGAS、STING、TNF-α、IL-6与IL-1β的蛋白表达水平。

结果：与正常组比较，模型组小鼠神经视网膜渗漏水平增加，视网膜变薄，视网膜凋亡水平上升并伴随着视网膜Iba1、GFAP表达水平的上调，Rhodopsin、Opsin表达下降。视网膜组织cGAS、STING、TNF-α、IL-6与IL-1β的蛋白表达水平均明显升高。与模型组比较，双丹明目胶囊组与阳性药物组小鼠神经视网膜渗漏水平降低，视网膜凋亡水平下降并伴随着视网膜Iba1、GFAP表达水平的下调，Rhodopsin、Opsin表达上调。视网膜组织cGAS、STING、TNF-α、IL-6与IL-1β的蛋白表达水平比较均明显下降，但双丹明目胶囊组与阳性药物组无显著差异。

结论：双丹明目胶囊可改善糖尿病视网膜病变小鼠视网膜炎症及早期损伤，其机制可能与抑制cGAS-STING信号途径有关。

METHODS:SPF C57BL/6J male mice were first randomly divided into two groups: a DR model group(n=30)receiving daily intraperitoneal STZ injections(50 mg/kg)for 5 d, and a normal control group(n=10)receiving equivalent sodium citrate buffer. After successful diabetes induction, the mice were randomly divided into model group, Shuangdan Mingmu Capsules group, and positive drug group, with 10 mice in each group. The Shuangdan Mingmu Capsules group received gavage with Shuangdan Mingmu Capsules solution at a clinically equivalent dose(11.2 g/kg), while the positive drug group received gavage with Calcium Dobesilate solution at an equivalent dose of 11.6 mg/kg. The model group and the normal group received gavage with an equal volume of normal saline. Each group of mice received gavage once daily, and after 8 weeks of intervention treatment, Evans blue staining was used to detect the retinal leakage in each group of mice, HE staining was used to detect changes in the retinal tissue structure, TUNEL staining was used to observe the apoptosis of retinal cells, and immunofluorescence was used to detect the expression levels of retinal Rhodopsin, Opsin, Iba1 and GFAP. Furthermore, Western blot was used to detect the protein expression levels of cGAS, STING, TNF-α, IL-6 and IL-1β in the mouse retina.

RESULTS:Compared with the normal group, the model group mice exhibited increased levels of neuroretinal leakage, retinal thinning, and elevated retinal cells apoptosis, accompanied by upregulation of Iba1 and GFAP expression levels in the retina, and downregulation of Rhodopsin and Opsin expression. The protein expression levels of cGAS, STING, TNF-α, IL-6, and IL-1β in the retinal tissue were significantly increased. In contrast to the model group, the Shuangdan Mingmu Capsules group and positive drug group mice showed decreased levels of neuroretinal leakage and retinal cells apoptosis, along with downregulation of Iba1 and GFAP expression levels in the retina, and upregulation of Rhodopsin and Opsin expression. The protein expression levels of cGAS, STING, TNF-α, IL-6, and IL-1β in the retinal tissue were significantly decreased. However, there was no significant difference between the Shuangdan Mingmu Capsules group and the positive drug group.

CONCLUSION:Shuangdan Mingmu Capsules exert therapeutic effects on retinal inflammation and early damage in DR mouse models, with the underlying mechanism involving the inhibition of the cGAS-STING signaling pathway.