抑制瞬时感受器电位香草素受体亚家族Ⅳ型通道对大鼠视网膜缺血-再灌注损伤后细胞凋亡与新生血管生成的作用  

Effect of inhibiting transient receptor potential vanilloid receptor subfamily typeⅣchannel on cell apoptosis and neovascularization in rats after retinal ischemia-reperfusion injury

作　　者：齐新刚 顾永欣 肖云 杜雷 QI Xin-gang;GU Yong-xin;XIAO Yun;DU Lei(Military Ophthalmology Center,Beijing Road Medical District,Xinjiang Military Command General Hospital of the Chinese People′s Liberation Army,Urumqi 830013,China;School of Basic Medicine,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]中国人民解放军新疆军区总医院北京路医疗区全军眼科中心,乌鲁木齐市830013 [2]新疆医科大学基础医学院,乌鲁木齐市830011

出　　处：《广西医学》2021年第15期1841-1846,共6页Guangxi Medical Journal

基　　金：新疆维吾尔自治区自然科学基金(2019D01C410)。

摘　　要：目的探讨抑制瞬时感受器电位香草素受体亚家族Ⅳ型(TRPV4)通道对大鼠视网膜缺血-再灌注损伤(RIRI)细胞凋亡和血管形成的影响。方法将30只SD大鼠分为对照组、RIRI组和RIRI+HC-067047组,每组10只。采用高眼压法建立大鼠RIRI模型,RIRI+HC-067047组在造模后5、10 h通过侧脑室注射HC-067047(5μmol/μL),对照组和RIRI组给予同等剂量的生理盐水。测量各组大鼠治疗后第7天、第14天与第21天的体质量,于治疗第21天观察大鼠视网膜组织形态变化和视网膜组织神经细胞凋亡情况,检测各组大鼠视网膜组织半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、血管内皮生长因子(VEGF)蛋白阳性表达情况,VEGF、核因子E2相关因子2(Nrf2)、缺氧诱导因子1α(HIF-1α)mRNA的相对表达水平,以及色素上皮衍生因子(PEDF)、胶质纤维酸性蛋白质(GFAP)、Caspase-3、B细胞淋巴瘤-2(Bcl-2)及Bcl-2相关X蛋白(Bax)的相对表达水平。结果与对照组比较,治疗后第21天RIRI组大鼠体质量下降,RIRI组和RIRI+HC-067047组视网膜组织神经细胞凋亡增加,Caspase-3、VEGF蛋白阳性表达率增加,Nrf2、VEGF、HIF-1αmRNA相对表达水平升高,PEDF、Bcl-2蛋白表达水平下降而GFAP、Caspase-3、Bax蛋白表达水平升高(均P<0.05)。与RIRI组比较,治疗后第21天,RIRI+HC-067047组视网膜神经细胞凋亡数目减少,Caspase-3、VEGF蛋白阳性表达率下降,Nrf2、VEGF、HIF-1αmRNA相对表达水平下降,PEDF、Bcl-2蛋白表达水平升高而GFAP、Caspase-3、Bax蛋白表达水平下降(均P<0.05)。结论抑制TRPV4通道可改善大鼠RIRI,其机制可能与抑制视网膜细胞凋亡与减少血管新生有关。Objective To investigate the effect of inhibiting transient receptor potential vanilloid receptor subfamily typeⅣ(TRPV4)channel on cell apoptosis and angiogenesis in rats after retinal ischemia-reperfusion injury(RIRI).Methods Thirty SD rats were divided into control group,RIRI group and RIRI+HC-067047 group,with 10 rats in each group.A rat RIRI model was established by using high intraocular pressure.The RIRI+HC-067047 group was injected with HC-067047(5μmol/μL)through the lateral ventricle five and 10 hours after modeling.The control and RIRI groups were given the same dose of normal saline.The body masses of rats in each group were measured on the 7th,14th and 21th day after treatment.On the 21th day of treatment,the morphological changes in rat retinal tissue and the apoptosis of retinal nerve cells were observed,and the relevant indices were detected in each group,including the positive expression of rat retinal cysteinyl aspartate specific proteinase 3(Caspase-3)and vascular endothelial growth factor(VEGF)proteins,the relative expression levels of VEGF,nuclear factor E2-related factor 2(Nrf2)and hypoxia-inducible factor 1α(HIF-1α)mRNAs,and the relative expression levels of pigment epithelial-derived factor(PEDF),glial fibrillary acidic protein(GFAP),Caspase-3,B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Results Compared with the control group,on the 21st day after treatment,rats in the RIRI group had decreased body mass,the RIRI and RIRI+HC-067047 groups exhibited increased nerve cell apoptosis in retinal tissue,elevated positive expression rates of Caspase-3 and VEGF proteins,higher relative expression levels of Nrf2,VEGF and HIF-1αmRNAs,lower expression levels of PEDF and Bcl-2 proteins,and elevated expression levels of GFAP,Caspase-3 and Bax proteins(all P<0.05).Compared with the RIRI group,on the 21st day after treatment,the RIRI+HC-067047 group reported decreased number of apoptotic retinal nerve cells,reduced positive expression rates of Caspase-3 and VEGF proteins,lower relative

关 键 词：视网膜缺血-再灌注 瞬时感受器电位香草素受体亚家族Ⅳ型通道 细胞凋亡 血管生成 

分 类 号：R774.1[医药卫生—眼科]