银杏叶提取物对氧诱导视网膜病变模型幼鼠视网膜增生变性的保护作用

Protective Effect of Extract of Ginkgo Biloba Leaf on the Retinal Hyperplasia and Degeneration of Neonatal Rats with Oxygen-induced Retinopathy

目的研究银杏叶提取物对氧诱导视网膜病变模型幼鼠视网膜凋亡相关基因的表达及其外周血血管内皮生长因子(vascular endothelial growth factor,VEGF)的影响,以明确其抑制视网膜增生变性的作用机制。方法选取清洁级出生7 d幼鼠100只,随机分为5组,每组20只。A组幼鼠由母鼠喂养,其余4组幼鼠均制成早产儿视网膜病变(retinopathy of prematurity,ROP)模型,出笼后B组幼鼠给予腹腔注射生理盐水,C、D、E组幼鼠分别给予腹腔注射4、2、1 mg/kg的银杏叶提取物,连续腹腔注射5 d后处死,取左侧眼球视网膜组织测定Bax与Bcl-2基因mRNA水平,采集右侧眼球静脉血检测VEGF浓度。结果 A组幼鼠视网膜组织Bax基因mRNA水平和Bax/Bcl-2高于其他4组(P<0.05),外周血Bcl-2基因mRNA水平和VEGF浓度低于其他4组(P<0.05)。B组幼鼠视网膜组织Bcl-2基因mRNA水平和外周血VEGF浓度高于其他4组(P<0.05),视网膜组织Bax基因mRNA水平和Bax/Bcl-2低于其他4组(P<0.05)。幼鼠视网膜组织Bcl-2基因mRNA水平和外周血VEGF浓度给药组间比较E组>D组>C组(P<0.05);Bax基因mRNA和Bax/Bcl-2水平给药组间比较E组<D组<C组(P<0.05)。Bax基因mRNA表达与Bcl-2基因mRNA表达之间存在显著负相关(r=-0.653,P<0.05);Bcl-2基因mRNA水平与VEGF浓度之间存在显著正相关(r=0.324,P<0.05)。结论银杏叶提取物可能是通过促进Bcl-2与VEGF表达、抑制Bax表达,从而发挥其抑制ROP幼鼠视网膜增生变性的作用,其抑制凋亡作用呈剂量-效应关系。

Objective To study the Extract of Ginkgo Biloba Leaf on the effects for retinal apoptosis of related gene expressions and vascular endothelial growth factor（ VEGF） of neonatal rats with oxygen-induced retinopathy so as to understand the mechanisms of inhibiting retinal hyperplasia and degeneration.Methods A total of 100 neonatal rats（ 7-d old） were randomly divided into five groups（ n = 20 for each group）.Group A was fed by female rats,and retinopathy of prematurity（ ROP） models were established in group B,C,D and E.After being let from the cage,group B was intraperitoneally injected with physiological saline,while group C,D and E were intraperitoneally injected with 4,2,1 mg / kg Extract of Ginkgo Biloba Leaf respectively.The rats were sacrificed after continuous injection for 5 d,and the retinal tissues in left eyeball were obtained to detect the mRNA levels of Bax and Bcl-2 genes,and venous blood in right eyeball was collected to detect VEGF concentration.Results In group A,the values of Bax mRNA level and Bax / Bcl-2 were higher（ P〈0.05）,while the values of Bcl-2 mRNA level and VEGF concentration were lower than those in other4 groups（ P〈0.05）.In group B,the values of Bcl-2 mRNA level and VEGF concentration were higher（ P〈0.05）,while the values of Bax mRNA level and Bax / Bcl-2 were lower than those in other 4 groups（ P〈0.05）.The values of Bcl-2 mRNA level and VEGF concentration in medication group from high to low were group E,D and C（ P〈0.05）;the values of Bax mRNA level and Bax / Bcl-2 in medication group from high to low were group E,D and C（ P〈0.05）.The mRNA expressions of Bcl-2 and Bax genes had significantly negative correlation（ r =-0.653,P〈0.05）.The Bcl-2 mRNA level was positively correlated with the VEGF concentration（ r = 0.324,P〈0.05）.Conclusion Extract of Ginkgo Biloba Leaf may inhibit the retinal hyperplasia and degeneration of ROP rats by increasing the expressing of Bcl-2 and VEGF and decreasing the Bax expression.The inhibition of apoptosis shows a dose effect relationship.