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

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

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。

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-αlevels,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-αlevels,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-αlevels,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.