替普瑞酮对急性高眼压大鼠视神经保护作用的实验研究
发布时间：2018-10-24 09:03
【摘要】： 目的青光眼目前已成为世界上最主要的致盲眼病之一,其典型表现是视神经乳头的凹陷性萎缩和视野的特征性缺损缩小。视网膜神经节细胞(retinal ganglion cells, RGCs)凋亡,一种高度调控的细胞死亡,是青光眼视神经损伤的最终共同通路。用药物或其他方法干预,使那些未受损的,仅部分受损的,或正处于毒性内环境中临近死亡的视网膜细胞得以存活或延长生存时间具有重大意义,也成为当前研究的热点。热休克蛋白70(heat shock protein 70,HSP70)是组织缺血损失时敏感而可靠的指标,HSP70表达的增强对神经组织具有保护作用。本实验通过制作急性高眼压大鼠模型,探讨替普瑞酮(geranylgeranylacetone, GGA)对大鼠视网膜HSP70表达的影响,及其对急性高眼压大鼠视神经的保护作用。 方法健康SD大鼠60只随机分为3组,分为健康对照组大鼠20只(A组)、急性高眼压对照组20只(B组)和GGA治疗组20只(C组),A组和B组给予生理盐水灌胃,C组给予替普瑞酮灌胃,一周后B组和C组采用前房加压法制作大鼠急性高眼压模型,A组不加任何干预措施。术后6h、24h、48h、72h处死动物,完整取出眼球,放人事先编号盛有10%中性甲醛的瓶中保存。石蜡包埋,制作切片。HE染色,光镜下观察再灌注后不同时间段各组鼠视网膜组织结构变化,采用免疫组织化学法检测大鼠视网膜HSP70和凋亡蛋白酶-3(Cysteine-containing aspartate-specific proteases-3, caspase-3)的表达,阳性结果为胞浆或胞核呈黄色或棕黄色染色。计数,采用SPSS16.0统计软件处理,采用独立样本t检验,P＜0.05表示差异有统计学意义。 结果术后A组均为正常视网膜结构。C组大鼠视网膜水肿较B组轻,各时间段C组大鼠视网膜内层厚度均较B组厚。B组HSP70在术后6h即有表达,随时间段延长表达逐渐增加,至再灌注后24 h达到高峰,之后渐下降。C组HSP70表达较之明显增强,差异有统计学意义(P＜0.05)。B组caspase-3于术后6h开始表达,并逐渐递增,24 h达到高峰,48h开始下降,72h仅有少量表达。C组caspase-3表达较之明显减弱,差异有统计学意义(P＜0.05)。A组几乎无HSP70和caspase-3的表达。 结论急性高眼压可以造成视神经缺血,引起视网膜水肿和RGCs凋亡,同时能诱导视网膜HSP70的表达。替普瑞酮能诱导视网膜HSP70的表达增强,对急性高眼压造成的视神经损伤起到保护作用。
[Abstract]:Objective at present, glaucoma has become one of the most important blinding eye diseases in the world. The typical manifestation of glaucoma is the concave atrophy of optic nipple and the reduction of characteristic defect of visual field. Retinal ganglion (retinal ganglion cells, RGCs) apoptosis, a highly regulated cell death, is the ultimate common pathway of glaucoma optic nerve injury. It is of great significance to intervene with drugs or other methods to make retinal cells that are not damaged, only partially damaged, or near death in toxic environment survive or prolong their survival time, which has also become a hot topic in current research. Heat shock protein 70 (HSP70) is a sensitive and reliable marker of ischemic tissue loss. The enhanced expression of HSP70 has protective effect on nerve tissue. To investigate the effect of tipranone (geranylgeranylacetone, GGA) on the expression of HSP70 in rat retina and its protective effect on optic nerve in rats with acute intraocular hypertension. Methods Sixty healthy SD rats were randomly divided into 3 groups: control group (n = 20), acute intraocular hypertension group (n = 20) and GGA treatment group (n = 20). One week later, group B and group C used anterior chamber pressure method to make acute intraocular hypertension model in rats, group A did not add any intervention measures. The animals were killed at 24 hours and 48 hours after operation. The eyeballs were taken out and stored in a bottle containing 10% neutral formaldehyde. The changes of retinal tissue structure were observed under light microscope at different time after reperfusion. The expression of HSP70 and apoptotic protease 3 (Cysteine-containing aspartate-specific proteases-3, caspase-3) in rat retina were detected by immunohistochemical method. The positive results were yellow or brown staining in cytoplasm or nucleus. The count was processed by SPSS16.0 statistical software, and the independent sample t test was used. The difference was statistically significant (P < 0. 05). Results the retinal edema in group C was lighter than that in group B. the thickness of inner retinal layer in group C was thicker than that in group B. the expression of HSP70 in group B was observed 6 hours after operation and increased gradually with the extension of time. The expression of HSP70 in group C was significantly higher than that in group C (P < 0. 05). The expression of caspase-3 in group C was significantly higher than that in group C (P < 0. 05). The expression of caspase-3 began at 6 hours after reperfusion (P < 0. 05). The expression of caspase-3 in group C was significantly lower than that in group C (P < 0. 05, P < 0. 05). The expression of HSP70 and caspase-3 was almost no in group C (P < 0. 05). Conclusion Acute intraocular pressure can induce optic nerve ischemia, retinal edema and RGCs apoptosis, and induce the expression of retinal HSP70. Tipranone can induce increased expression of HSP70 in retina and protect optic nerve injury caused by acute intraocular pressure.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R775
[Abstract]:Objective at present, glaucoma has become one of the most important blinding eye diseases in the world. The typical manifestation of glaucoma is the concave atrophy of optic nipple and the reduction of characteristic defect of visual field. Retinal ganglion (retinal ganglion cells, RGCs) apoptosis, a highly regulated cell death, is the ultimate common pathway of glaucoma optic nerve injury. It is of great significance to intervene with drugs or other methods to make retinal cells that are not damaged, only partially damaged, or near death in toxic environment survive or prolong their survival time, which has also become a hot topic in current research. Heat shock protein 70 (HSP70) is a sensitive and reliable marker of ischemic tissue loss. The enhanced expression of HSP70 has protective effect on nerve tissue. To investigate the effect of tipranone (geranylgeranylacetone, GGA) on the expression of HSP70 in rat retina and its protective effect on optic nerve in rats with acute intraocular hypertension. Methods Sixty healthy SD rats were randomly divided into 3 groups: control group (n = 20), acute intraocular hypertension group (n = 20) and GGA treatment group (n = 20). One week later, group B and group C used anterior chamber pressure method to make acute intraocular hypertension model in rats, group A did not add any intervention measures. The animals were killed at 24 hours and 48 hours after operation. The eyeballs were taken out and stored in a bottle containing 10% neutral formaldehyde. The changes of retinal tissue structure were observed under light microscope at different time after reperfusion. The expression of HSP70 and apoptotic protease 3 (Cysteine-containing aspartate-specific proteases-3, caspase-3) in rat retina were detected by immunohistochemical method. The positive results were yellow or brown staining in cytoplasm or nucleus. The count was processed by SPSS16.0 statistical software, and the independent sample t test was used. The difference was statistically significant (P < 0. 05). Results the retinal edema in group C was lighter than that in group B. the thickness of inner retinal layer in group C was thicker than that in group B. the expression of HSP70 in group B was observed 6 hours after operation and increased gradually with the extension of time. The expression of HSP70 in group C was significantly higher than that in group C (P < 0. 05). The expression of caspase-3 in group C was significantly higher than that in group C (P < 0. 05). The expression of caspase-3 began at 6 hours after reperfusion (P < 0. 05). The expression of caspase-3 in group C was significantly lower than that in group C (P < 0. 05, P < 0. 05). The expression of HSP70 and caspase-3 was almost no in group C (P < 0. 05). Conclusion Acute intraocular pressure can induce optic nerve ischemia, retinal edema and RGCs apoptosis, and induce the expression of retinal HSP70. Tipranone can induce increased expression of HSP70 in retina and protect optic nerve injury caused by acute intraocular pressure.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R775
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