血红素氧合酶-1对糖尿病大鼠视网膜神经节细胞的保护作用

发布时间：2018-04-26 21:02

本文选题：糖尿病视网膜病变 + 血红素氧合酶-　；参考：《中国老年学杂志》2017年21期

【摘要】：目的探讨血红素氧合酶(HO)-1对糖尿病(DM)大鼠视网膜神经节细胞(RGC)保护作用及其机制。方法清洁级雄性SD大鼠24只中8只为对照组,余16只腹腔注射链脲佐菌素制作DM大鼠模型,将血糖浓度大于16.7 mmol/L的大鼠定为DM模型,随机分为DM组8只,另外8只腹腔注射HO-1特异性诱导剂正铁血红素为实验组,对照组及DM组腹腔注射等剂量生理盐水。12 w后,HE染色观察RGC密度,硫代巴比妥酸法检测丙二醛(MDA)含量,氮蓝四唑光化还原法测定超氧化物歧化酶(SOD)活性,免疫组化染色和Western印迹法检测视网膜HO-1、Caspase-3表达情况。结果与对照组相比,DM组RGC密度显著降低(P0.01),而实验组无明显变化(P0.05)。与对照组相比,DM组MDA含量明显升高、SOD活性明显降低(P0.01),而实验组无明显变化(P0.05)。HO-1在对照组仅微量表达于内核层,DM组阳性表达在节细胞层及内核层有所增加,而实验组阳性染色显著增加,特别是节细胞层。Caspase-3在对照组视网膜几乎无表达,而DM组阳性表达显著增多,主要分布于节细胞层及内核层,实验组与DM组相比阳性表达有所减弱。与对照组相比,HO-1在DM组及实验组蛋白表达量均增加(P0.01),且实验组增加更明显(P0.05);与对照组相比,Caspase-3在DM组蛋白表达显著增加(P0.01),而实验组无明显变化。结论通过正铁血红素诱导HO-1在视网膜的高表达,下调了DM大鼠视网膜Caspase-3的表达,抑制了氧化应激,恢复了视网膜RGC密度;提示HO-1可能对DM大鼠RGC具有保护作用。
[Abstract]:Objective to investigate the protective effect and mechanism of heme oxygenase-1 (HO-1) on retinal ganglion cells (RGCCs) in diabetic rats. Methods Twenty four male SD rats of clean grade were used as control group. The remaining 16 rats were treated with streptozotocin intraperitoneally to make DM model. The rats whose blood glucose concentration was more than 16.7 mmol/L were randomly divided into DM group (n = 8) and DM group (n = 8). The other 8 rats were given intraperitoneal injection of HO-1 specific inducer normal heme as experimental group, control group and DM group were injected intraperitoneally with the same dose of normal saline for 12 weeks to observe the density of RGC and the content of malondialdehyde (malondialdehyde) by thiobarbituric acid method. The activity of superoxide dismutase (SOD) was determined by photochemical reduction of azolium tetrazole, and the expression of HO-1Caspase-3 in retina was detected by immunohistochemical staining and Western blotting. Results compared with the control group, the density of RGC in DM group was significantly lower than that in control group (P 0.01), but there was no significant change in experimental group (P 0.05). Compared with the control group, the content of MDA in DM group increased significantly and the activity of MDA decreased significantly, while in the experimental group, there was no significant change in P0.05. HO-1 expression in the control group was only slightly expressed in the kernel-layer DM group, and the positive expression was increased in the ganglion cell layer and the kernel layer. The positive staining in the experimental group was significantly increased, especially in the ganglion cell layer. Caspase-3 was almost not expressed in the retina of the control group, while the positive expression of Caspase-3 in the DM group was significantly increased, mainly distributed in the ganglion cell layer and the nuclear layer. Compared with the DM group, the positive expression of Caspase-3 in the experimental group was weakened. Compared with the control group, the protein expression of pHO-1 increased in DM group and experimental group, and increased more obviously in experimental group than that in control group, and the expression of caspase-3 in DM group increased significantly compared with control group, but there was no significant change in experimental group. Conclusion the high expression of HO-1 in the retina induced by heme can down-regulate the expression of Caspase-3 in the retina of DM rats, inhibit oxidative stress and restore the density of RGC in the retina, suggesting that HO-1 may have a protective effect on RGC of DM rats.
【作者单位】：锦州医科大学人体解剖学教研室;锦州医科大学附属第三医院检验科;
【基金】：国家自然科学基金资助项目(No.81571383)
【分类号】：R587.2;R774.1

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