神经退化与糖尿病视网膜病变相关性研究

发布时间：2018-07-31 13:58

【摘要】：目的：糖尿病可以诱发视网膜细胞凋亡,同时诱发神经系统、血浆出现感觉神经递质降钙素基因相关肽(calcitonin gene-related peptide, CGRP)和P物质(substance P, SP)的耗损,辣椒素可引起CGRP和SP等感觉神经递质释放并且参与器官保护,然而CGRP和SP在糖尿病视网膜病变细胞凋亡中的作用如何尚待阐明。观察分析链脲佐菌素(streptozocin, STZ)诱发的糖尿病视网膜病变(Diabetic Retinopathy, DR)大鼠视网膜细胞病理学改变及凋亡与视网膜和血清中感觉神经递质CGRP和SP变化的关系；探讨辣椒素预处理对糖尿病视网膜病变大鼠视网膜组织和血清中CGRP和SP的表达变化及其对糖尿病视网膜细胞凋亡的保护作用。方法：将健康成年雄性SD大鼠40只(80只眼)随机分为5组,每组8只(16眼)。DR组：1%STZ溶液腹腔注射给药；药物干预组：前三天皮下注射1%辣椒素溶液(20mg/kg),第四天腹腔注射1%STZ溶液；DR对照组和药物干预对照组分别给予上述药物的等量溶剂；空白对照组：不做任何处理。糖尿病大鼠造模后饲养10周,组织病理切片证实糖尿病视网膜病变大鼠模型造模成功。检测各组视网膜细胞凋亡率及caspase-3(?)舌性,视网膜和血清中CGRP和SP的表达变化。结果：DR组的视网膜神经节层细胞凋亡率(43.4%±5.0%)高于药物干预组(30.0%±5.1%),差异有统计学意义(t=5.930,P0.01)；DR对照组和药物干预对照组的视网膜细胞凋亡率分别为(12.4%±9.9%,17.6%±6.1%),与各自实验组比较,差异有统计学意义(t=8.800,t=4.925,P0.01)。空白组细胞凋亡率为(16.2%±6.9%),与两个对照组比较,差异无统计学意义(t=-0.989, t=0.951, P0.05). DR组大鼠视网膜中caspase-3比活性值为(2.19±0.86),药物干预组为(1.96±0.56),差异有统计学意义(t=-0.515,P0.05)。DR对照组和药物干预对照组的比活性值分别为(1.47±0.14)和(0.74±0.27),与各自实验组比较,差异有统计学意义(t=2.797,t=2.142, P0.05)。DR组视网膜CGRP含量为(424.4±44.2pg/ml),药物干预组为(543.2±74.4pg/ml),两组比较差异有统计学意义(t=3.070,P0.05); DR组血清CGRP含量为(148.8±39.1pg/ml),药物干预组血清CGRP含量(237.5±78.7pg/ml),差异有统计学意义(t=2.359,P0.05)。DR组视网膜SP含量为(20.42±0.94ng/ml),药物干预组为(24.08±3.34ng/ml),两组比较差异有统计学意义(t=2.142,P0.05); DR对照组视网膜SP含量为(26.69±7.74ng/ml),与DR组比较差异有统计学意义(t=-1.587,P0.05); DR组血清SP含量为(10.32±1.14ng/ml),药物干预组血清SP含量为(12.89±1.52ng/ml),差异有统计学意义(t=3.017,P0.05); DR对照组血清SP含量为(12.24±0.63ng/ml),与DR组比较差异有统计学意义(t=-3.554,P0.05) 结论：DR可引起视网膜神经节细胞凋亡显著增加,视网膜组织和血清CGRP和SP水平的下降,小剂量辣椒素可诱导糖尿病视网膜组织和血清CGRP和SP水平上调,减轻视网膜细胞凋亡,对抗DR引起的视网膜组织损伤。提示糖尿病大鼠视网膜组织和血清CGRP和SP水平的下降可能与DR引起视网膜神经节细胞凋亡增加有关,CGRP和SP可能参与对DR引起的视网膜细胞凋亡的保护作用。
[Abstract]:Objective: diabetes can induce apoptosis of retina cells and induce the nervous system, and the loss of calcitonin gene-related peptide (CGRP) and P substance (substance P, SP) in plasma, capsaicin can cause the release of sensory neurotransmitters such as CGRP and SP and participate in organ protection. The role of SP in the apoptosis of diabetic retinopathy remains to be elucidated. The relationship between the pathological changes of retinal cell pathology and the relationship between apoptosis and the changes of the sensory neurotransmitters CGRP and SP in the retina and serum of the diabetic retinopathy (Diabetic Retinopathy, DR) induced diabetic retinopathy (Diabetic Retinopathy, DR) induced by streptozotocin (STZ) was investigated. Capsaicin preconditioning protects the expression of CGRP and SP in the retina tissue and serum of diabetic retinopathy rats and the protective effect of capsaicin on the apoptosis of diabetic retina cells.
Methods: 40 healthy adult male SD rats (80 eyes) were randomly divided into 5 groups, each group of 8 (16 eyes) group.DR: 1%STZ solution intraperitoneal injection; drug intervention group: the first three days the subcutaneous injection of 1% capsaicin solution (20mg/kg), fourth days intraperitoneal injection of 1%STZ solution; DR control group and drug intervention control group to give the same amount of drugs to the same amount, respectively. In the blank control group, no treatment was done in the control group. The diabetic rat model was fed for 10 weeks. The histopathological section confirmed the success of the diabetic retinopathy model. The apoptosis rate of retinal cells and the caspase-3 (?) tongue, the expression of CGRP and SP in the retina and serum were detected.
Results: the apoptosis rate of retinal ganglion layer cells in DR group (43.4% + 5%) was higher than that of the drug intervention group (30% + 5.1%), and the difference was statistically significant (t=5.930, P0.01). The apoptosis rate of retinal cells in the DR control group and the drug intervention control group were (12.4% + 9.9%, 17.6% + 6.1%) respectively, and the difference was statistically significant (t=8.800, t). =4.925, P0.01). The cell apoptosis rate in the blank group was (16.2% + 6.9%). Compared with the two control groups, the difference was not statistically significant (t=-0.989, t=0.951, P0.05). The caspase-3 ratio activity in the retina of the DR group was (2.19 + 0.86), and the drug intervention group was (1.96 + 0.56), the difference was statistically significant (t=-0.515, P0.05).DR control group and drug intervention control group The specific activity values were (1.47 + 0.14) and (0.74 + 0.27) respectively. Compared with the experimental group, the difference was statistically significant (t=2.797, t=2.142, P0.05).DR group CGRP content was (424.4 + 44.2pg/ml), the drug intervention group was (543.2 + 74.4pg/ml), the two groups were statistically significant (t=3.070, P0.05); DR group serum CGRP content was (148.8 + 39.1p). G/ml), the serum CGRP content of the drug intervention group (237.5 + 78.7pg/ml), the difference was statistically significant (t=2.359, P0.05).DR group retinal SP content was (20.42 + 0.94ng/ml), the drug intervention group was (24.08 + 3.34ng/ml), the two groups were statistically significant (t=2.142, P0.05), and the retina content of the retina was (26.69 +), and was worse than that of the group. The difference was statistically significant (t=-1.587, P0.05); the serum SP content in DR group was (10.32 + 1.14ng/ml), and the serum SP content of the drug intervention group was (12.89 + 1.52ng/ml), the difference was statistically significant (t=3.017, P0.05), and the SP content of the serum of DR control group was (12.24 + 0.63ng/ml).
Conclusion: DR can cause a significant increase in retinal ganglion cell apoptosis, the decrease of CGRP and SP levels in retinal tissue and serum. Small dose capsaicin can induce the up-regulation of CGRP and SP levels in diabetic retina tissue and serum, alleviate retinal cell apoptosis and antagonism the damage of retinal membrane tissue caused by DR, suggesting the retina tissue of diabetic rats The decrease of CGRP and SP levels in serum may be associated with increased apoptosis of retinal ganglion cells caused by DR, and CGRP and SP may be involved in the protection of retinal cell apoptosis induced by DR.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R774.1

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