黄芩苷调节IL-33/ST2信号通路对糖尿病视网膜病变大鼠视网膜新生血管生成的影响北大核心

目的探讨黄芩苷调节白细胞介素(IL)-33/基质裂解素2(ST2)信号通路对糖尿病视网膜病变(DR)大鼠视网膜新生血管生成的影响。方法SD大鼠随机分为对照组(正常大鼠,灌胃生理盐水)、DR模型组(大鼠建立DR模型后,灌胃生理盐水)和黄芩苷低、中、高剂量组(大鼠建立DR模型后,分别灌胃75 mg·kg^(-1)、150 mg·kg^(-1)、300 mg·kg^(-1)黄芩苷),所有大鼠均以右眼为实验眼。FFA检查各组大鼠视网膜血管生成情况,ELISA检测各组大鼠血清血管内皮生长因子(VEGF)、Ang-1、IL-6、IL-33、肿瘤坏死因子-α(TNF-α)水平,Western blot检测各组大鼠视网膜组织中IL-33、ST2蛋白表达水平。结果与对照组相比,DR模型组大鼠血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平及视网膜组织中IL-33、ST2蛋白表达水平均显著升高(均为P<0.05),右眼眼底新生血管增多,荧光素渗漏明显;与DR模型组相比,黄芩苷低、中、高剂量组大鼠血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平及视网膜组织中IL-33、ST2蛋白表达水平均显著降低(均为P<0.05),右眼视网膜新生血管生成减少,荧光素渗漏减少;随着黄芩苷剂量的升高,大鼠血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平及视网膜组织中IL-33、ST2蛋白表达水平均逐渐降低(均为P<0.05)。结论黄芩苷能抑制IL-33/ST2信号通路激活,减轻DR大鼠体内炎症水平,减少视网膜新生血管生成。

Effect of baicalin on retinal neovascularization in rats with diabetic retinopathy by regulating interleukin-33/stromal lysin 2 signaling pathway

Objective　To investigate the effect of baicalin on retinal neovascularization in diabetic retinopathy (DR) rats by regulating the interleukin (IL)-33/stromal lysin 2 (ST2) signaling pathway. Methods　SD rats were randomly divided into the control group (normal rats, intragastric administration of saline), DR model group (DR rats, intragastric administration of saline), low-, medium-, and high-dose baicalin groups (DR rats, intragastric administration of 75 mg·kg^-1, 150 mg·kg^-1, and 300 mg·kg^-1 baicalin, respectively). The experiment was carried out in the right eyes. The retinal angiogenesis was evaluated by FFA. The levels of serum vascular endothelial growth factor (VEGF), Ang-1, IL-6, IL-33, and tumor necrosis factor-α (TNF-α) were measured by ELISA. The IL-33 and ST2 protein levels in retinal tissues were detected by Western blot. Results　Compared with the control group, the serum VEGF, Ang-1, IL-6, IL-33, and TNF-α levels, as well as the IL-33 and ST2 protein levels in the DR model group increased significantly (all P<0.05); similarly, the fundus neovascularization in the right eyes and fluorescein leakage also increased. Compared with the DR model group, the serum VEGF, Ang-1, IL-6, IL-33, and TNF-α levels, as well as the IL-33 and ST2 protein levels in the low-, medium-, and high-dose baicalin groups decreased significantly (all P<0.05); similarly, the retinal neovascularization in the right eyes and fluorescein leakage also decreased. With the increase of baicalin dose, the serum VEGF, Ang-1, IL-6, IL-33, and TNF-α levels, as well as the IL-33 and ST2 protein levels decreased gradually (all P<0.05). Conclusion　Baicalin can inhibit the activation of the IL-33/ST2 signaling pathway and reduce inflammation and retinal neovascularization in DR rats.