飞燕草素对大鼠视网膜缺血-再灌注损伤和脂肪酸合成酶、凋亡相关因子配体蛋白表达的影响  

Effects of delphinidin on retinal ischemia-reperfusion injury and expression of Fas and FasL proteins in rats

作　　者：王哲[1] 李海英[1] 姚雪[1] WANG Zhe;LI Hai-ying;YAO Xue(Department of Ophthalmology,Zibo Central Hospital,Zibo 255000,Shandong Province,China)

机构地区：[1]淄博市中心医院眼科,山东淄博255000

出　　处：《中国临床药理学杂志》2020年第22期3786-3789,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨飞燕草素对大鼠视网膜缺血-再灌注损伤(retina ischemia-reperfusion injury,RIRI)和脂肪酸合成酶(Fas)、凋亡相关因子配体(FasL)蛋白表达的影响。方法健康雄性SD大鼠随机分为对照组、模型组及低、中、高剂量实验组(25,50,100 mg·kg^-1飞燕草素),各12只。建模前连续3 d实验组分别灌服各剂量Dp,每天1次,对照组及模型组则灌服等量的生理盐水,于末次给药30 min后采用高眼压法建立RIRI模型,建模24 h后颈椎脱臼处死大鼠。以HE染色观察视网膜形态学变化,测定视网膜内层厚度及神经节细胞数;以TUNEL法检测视网膜神经细胞凋亡情况;以免疫组化法检测视网膜半胱氯酸蛋白酶-3(Caspase-3)蛋白的表达;以Western blot检测视网膜组织中Fas及FasL蛋白表达。结果给药后,正常组、模型组和低、中、高剂量实验组大鼠的视网膜厚度为(48.56±2.42),(64.41±4.58),(60.27±3.47),(56.39±3.31),(52.25±2.71)μm;神经节细胞数为(554.67±10.24),(309.78±9.89),(375.95±11.57),(428.38±8.78),(476.81±10.54)个/mm2;神经细胞凋亡数为(42.14±4.37),(245.67±12.83),(200.16±9.46),(162.49±6.69),(110.72±8.19)个/mm2,各组间比较上述指标差异均有统计学意义(P<0.05)。与模型组比较,高、中、低剂量实验组大鼠TUNEL及Caspase-3阳性细胞数均显著减少(P<0.01),高、中剂量实验组大鼠视网膜组织中Fas及FasL蛋白相对表达量均明显降低(P<0.05)。结论飞燕草素对RIRI模型大鼠可减轻RIRI大鼠视网膜细胞凋亡,具有神经保护作用,可能与抑制视网膜中Caspase-3活化,抑制Fas/FasL凋亡通路蛋白表达有关。Objective To investigate the effects of delphinidin(Dp) on retina ischemia-reperfusion injury(RIRI) and the expression of Fas and FasL protein in rats. Methods Healthy male SD rats were randomly divided into control group, model group, and test-L group, test-M group,test-H group of delphinidin(25, 50, 100 mg·kg^-1 Dp), 12 rats each. Before the modeling, the experimental group was infused with Dp at different doses once a day for 3 days. The control group and model group were given the same amount of normal saline. The RIRI model was established by the ocular hypertension method after 30 minutes of the last dose and modeled for 24 hours. The rats were killed after dislocation of the cervical spine. HE staining was used to observe the morphological changes of the retina,the thickness of the inner layer of the retina and the number of ganglion cells were measured;the apoptosis of retinal nerve cells was detected by the TUNEL method;the expression of Caspase-3 protein was detected by immunohistochemistry;Fas and FasL protein expression. Results After administration,the retinal thickness of rats in the normal group,model group,and test-L/-M/-H group were(48. 56 ± 2. 42),(64. 41 ± 4. 58),(60. 27 ± 3. 47),(56. 39 ± 3. 31),(52. 25 ± 2. 71) μm,the number of ganglion cells were(554. 67 ± 10. 24),(309. 78 ± 9. 89),(375. 95 ± 11. 57),(428. 38 ± 8. 78),(476. 81 ± 10. 54)/mm2,and the number of nerve cell apoptosis were(42. 14 ± 4. 37),(245. 67 ± 12. 83),(200. 16 ± 9. 46),(162. 49 ± 6. 69),(110. 72 ± 8. 19)/mm2, the above indicators were statistically different between groups(P < 0. 05). Compared with the model group,the number of TUNEL and Caspase-3 positive cells in the test-L/-M/-H group was significantly reduced(P < 0. 01). And the relative expression of FasL protein was significantly reduced(P < 0. 05). Conclusion Dp can reduce the apoptosis of retinal cells in RIRI rats,and it may have neuroprotective effects,which may be related to inhibiting Caspase-3 activation in retina and inhibiting Fas/FasL apoptos

关 键 词：视网膜缺血-再灌注损伤 飞燕草素 脂肪酸合成酶 凋亡相关因子配体蛋白 

分 类 号：R28[医药卫生—中药学]