摘要
目的探讨芹菜素对烧灼表层巩膜静脉致青光眼大鼠视神经损伤的保护作用及机制。方法采用烧灼巩膜表面静脉法构建大鼠青光眼模型,并将模型大鼠随机分为模型组,芹菜素低、中、高剂量(20、40、80 mg/kg)组,Nec-1组,另设假手术组不进行灼烧。测量大鼠左眼术前、术后1 d、末次给药后2 h眼压,试剂盒检测大鼠视网膜活性氧(ROS)、丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性,HE染色评价视网膜损伤情况,荧光金逆行标记大鼠视网膜神经节细胞,视网膜捕片观察视网膜神经节细胞及细胞计数,Western blot法检测肿瘤坏死因子受体(TNFR)、受体相互作用蛋白激酶(RIPK)、半胱氨酸天冬氨酸蛋白酶-3(caspase-3)表达。结果与假手术组比较,术后1 d及末次给药后2 h,模型组大鼠眼压升高(P<0.05);与模型组比较,末次给药后2 h,芹菜素各剂量组和Nec-1组大鼠眼压降低(P<0.05),而且芹菜素作用呈剂量依赖性。与模型组比较,芹菜素各剂量组和Nec-1组大鼠视网膜神经纤维层厚度增厚,视网膜SOD活性和视网膜神经节细胞数升高(P<0.05),视网膜ROS、MDA水平及TNFR1、RIPK1、RIPK3、caspase-3蛋白表达降低(P<0.05),而且芹菜素作用呈剂量依赖性。结论芹菜素能够抑制视网膜神经节细胞的死亡从而保护青光眼大鼠视神经损伤,其机制可能与抑制TNFR/RIPK通路活性有关。
AIM To investigate the protective effect and mechanism of apigenin on optic nerve injury in rats with glaucoma induced by cauterization of episcleral vein.METHODS The rat models of glaucoma constructed by cauterization of scleral surface vein were randomly divided into the model group,the low,medium and high dose apigenin groups(20,40,80 mg/kg),and Nec-1 group,in addition to a sham operation group with no cauterization conducted upon the rats.The rats had the left eye intraocular pressure measured before the operation,1 d after operation and 2 h after the last dose,respectively;their levels of reactive oxygen species(ROS)and malondialdehyde(MDA),and the activity of superoxide dismutase(SOD)in the retina detected by the kit;their retinal injury assessed by HE staining;their retinal ganglion cells retrograde labeled with fluorescent gold and counted by retinal sections;and their expressions of tumor necrosis factor receptor(TNFR),receptor-interacting protein kinase(RIPK)and caspase-3 detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased intraocular pressure 1 d after operation and 2 h after the last administration(P<0.05).Compared with the model group,apigenin groups and Nec-1 group showed dose-dependent decrease of intraocular pressure 2 h after the last administration(P<0.05);increases in the thickness of retinal nerve fiber layer,the activity of retinal SOD and the number of retinal ganglion cells(P<0.05),and decreases of the levels of retinal ROS and MDA as well as the protein expressions of TNFR1,RIPK1,RIPK3 and caspase-3(P<0.05).CONCLUSION Apigenin can inhibit the death of retinal ganglion cells and thus protect the optic nerve injury in glaucoma rats,and its mechanism may be related to the inhibition of TNFR/RIPK pathway activity.
作者
郑永瑜
ZHENG Yong-yu(Department of Pharmacy,The Hospital Affiliated to Qinghai University;Department of Ophthalmology,The Hospital Affiliated to Qinghai University,Xining 810000,China)
出处
《中成药》
CAS
CSCD
北大核心
2023年第4期1126-1131,共6页
Chinese Traditional Patent Medicine
基金
2019年青海省新开科技计划项目(2019-ZJ-7064)。
作者简介
郑永瑜(1986-),男,主管药师,从事临床药学研究。Tel:13897189051,E-mail:kitty2893@163.com。
