摘要
目的 探讨雷公藤内酯醇(TPL)减轻糖尿病性白内障模型大鼠视网膜和白内障病变的作用及其机制。方法 将50只大鼠随机分为空白对照组(A组),模型对照组(B组),TPL低、中、高剂量组(C_(1)组、C_(2)组、C_(3)组),各10只。除A组外,其余各组大鼠腹腔注射链脲佐菌素(溶于pH 4.5的0.1 mol/L柠檬酸缓冲液中)60 mg/kg,以诱导糖尿病性白内障和视网膜病变。C_(1)组、C_(2)组、C_(3)组大鼠腹腔注射10,25,50 mg/kg TPL,A组、B组大鼠腹腔注射等量生理盐水,持续10周。采用血糖仪测定空腹血糖;观察给药后大鼠的晶状体混浊度,评估白内障严重程度;采用苏木精-伊红(HE)染色,观察眼球横切面视网膜的组织病理学和形态学变化;测定吸光度,考察大鼠晶状体上清液中丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GR)、醛糖还原酶(AR)、超氧化物歧化酶(SOD)、p38促分裂原活化蛋白激酶(p38 MAPK)、细胞外调节蛋白激酶1/2(ERK1/2)、血管内皮生长因子(VEGF)的活性。结果 眼球横切面视网膜的组织病理学HE染色切片显示,C_(1)组、C_(2)组、C_(3)组大鼠存在晶状体纤维和前上皮细胞,并伴均质化区域;形态学HE染色切片显示,C_(1)组、C_(2)组、C_(3)组大鼠外核层和内核层的排列疏松现象、神经节细胞数量均明显改善。与B组比较,C_(1)组、C_(2)组、C_(3)组大鼠的空腹血糖、晶状体浑浊度分级、白内障严重程度分级及晶状体上清液中MDA,AR,p38 MAPK,ERK1/2,VEGF水平均显著降低(P<0.05),视网膜总厚度、外核层视网膜厚度、视网膜神经节层中神经元数量及晶状体上清液中CAT,SOD,GR水平均显著升高(P<0.05)。结论 TPL为潜在的治疗糖尿病眼部并发症的药物,如视网膜和白内障病变。TPL可能通过抑制AR、抗氧化作用、MAPK信号传导来发挥保护作用,特别是通过下调ERK1/2,p38 MAPK,VEGF的表达。
Objective To investigate the effect and mechanism of triptolide(TPL)on alleviating retinal and cataract lesions in diabetes cataract(DC)model rats.Methods A total of 50 rats were randomly divided into the blank control group(group A),the model control group(group B),and TPL low-,medium-,and high-dose groups(groups C_(1),C_(2),and C_(3)),with 10 rats in each group.Except for the rats in group A,rats in other groups were intraperitoneally injected with 60 mg/kg of streptozotocin(dissolved in 0.1 mol/L citric acid buffer with pH 4.5)to induce DC and diabetes retinopathy(DR).Rats in groups C_(1),C_(2),and C_(3) were intraperitoneally injected with 10,25,and 50 mg/kg of TPL,while rats in groups A and B were intraperitoneally injected with an equal volume of physiological saline.All groups were treated for 10 weeks.Blood glucose meter was used to measure the fasting blood glucose(FBG).The opacity of the rat lens after administration was observed to evaluate the severity of cataracts.Hematoxylin-eosin(HE)staining was used to observe the histopathological and morphological changes of the retina in the cross-section of the eyeball.The absorbance was measured to investigate the activities of malondialdehyde(MDA),catalase(CAT),glutathione reductase(GR),aldose reductase(AR),superoxide dismutase(SOD),p38 mitogen activated protein kinase(p38 MAPK),extracellular regulated protein kinase 1/2(ERK1/2),and vascular endothelial growth factor(VEGF)in the supernatant of lenses.Results HE staining of the histopathological sections of the retina in the cross-section of the eyeball showed rats in groups C_(1),C_(2),and C_(3) had lens fibers and anterior epithelial cells,accompanied by homogenized areas.HE staining of the morphological sections showed rats in groups C_(1),C_(2),and C_(3) had loose arrangement of the outer and inner nuclear layers,and a significant improvement in the number of ganglion cells.Compared with those in group B,the FBG,lens opacity grading,cataract severity grading,and MDA,AR,p38 MAPK,ERK1/2,and VEGF levels in the lens supernatant of rats in groups C_(1),C_(2),and C_(3) significantly reduced(P<0.05),while the total retinal thickness,outer nuclear layer retinal thickness,number of neurons in the retinal ganglion layer,and average levels of CAT,SOD,and GR in the lens supernatant in groups C_(1),C_(2),and C_(3) significantly increased(P<0.05).Conclusion TPL is a potential drug for the treatment of ocular complications of diabetes,such as DR and DC.TPL may exert eye protection by inhibiting AR,antioxidant activity,and MAPK signaling,particularly by down-regulating the expression of ERK1/2,p38 MAPK,and VEGF levels.
作者
张历浊
李忠政
金蕊
ZHANG Lizhuo;LI Zhongzheng;JIN Rui(Qinhuangdao Optometry and Ophthalmology Hospital,Qinhuangdao,Hebei,China 066000)
出处
《中国药业》
2025年第5期42-47,共6页
China Pharmaceuticals
基金
河北省重点研发计划项目[22077710434D]。
作者简介
第一作者:张历浊,男,大学本科,副主任医师,研究方向为近视手术矫正,(电子信箱)493408715@163.com。
