摘要
研究目的：
通过观察JNK2在早期糖尿病视网膜病变小鼠病程中的表达变化以及视网膜中神经节细胞的凋亡情况,探讨JNK2在糖尿病视网膜病变(DR)早期的作用机制,并为进一步深入探讨糖网病的发病机制及早期治疗研究提供理论依据。
研究方法：
C57BL/6雄性小鼠随机分为实验组及对照组,实验组一次性腹腔注射1%STZ诱发糖尿病模型,对照组腹腔注射同剂量的柠檬酸钠缓冲液,成模后2、4、8周,分别取出小鼠眼球,左眼提取视网膜用于RT-real-time PCR,检测JNK2在不同时期mRNA的表达变化,右眼取出眼球行HE染色和TUNEL法,分别观察视网膜在各期的形态学改变及视网膜神经节细胞的凋亡情况。
研究结果：
1:JNK2在DM视网膜中的表达情况：正常组小鼠在各期的表达变化无明显差异,糖尿病2周组小鼠与同期正常组小鼠JNK2表达量无显著差异(t=-0.109,p=0.915>0.05);1月组糖尿病比同期正常组小鼠JNK2表达上调(p=0.002<0.05);2月组JNK2表达量明显上调(p=0.000<0.01)。
2：神经节细胞凋亡率：正常组小鼠神经节细胞可有少量凋亡,且各组间无统计学差异；糖尿病2周时神经节细胞凋亡不明显(组间比较p=0.086>0.05);糖尿病1月时视网膜神经节细胞层可见部分凋亡细胞(组间比较p=0.000<0.01);糖尿病2月时神经节细胞层凋亡细胞明显增多,内核层和外核层也可见凋亡细胞(组间比较p=0.000<0.01)。
3：HE染色及神经节细胞计数：正常组视网膜分层清晰,RGCS排列整齐,内丛状层染色较均匀,内核层和外核层细胞排列较整齐,视锥细胞、视杆细胞排列整齐;2周组糖尿病小鼠视网膜各层与正常组无明显变化,实验组小鼠1月时视网膜组织分层稍紊乱,细胞形态正常,但较稀疏;DM 2月组神经节细胞数目减少较明显,神经纤维层及内丛状层变薄,内核层细胞排列较紊乱,外丛状层厚度亦变薄,外界膜模糊,视杆细胞层细胞排列紊乱。神经节细胞2周组糖尿病与正常组比较无统计学差异(组间比较p=0.137>0.05),糖尿病1月组小鼠神经节细胞数开始变少(组间比较p=0.000>0.05)：两月组节细胞数量进一步减少(组间比较p=0.000>0.05)。
结论：
1：糖尿病视网膜病变的发生是多种因素,多种途径共同调控的复杂过程。
2：JNK2可能是糖尿病视网膜病变早期的重要调控因素之一,其表达与DM的病程密切相关。
3：JNK2的表达量与视网膜神经节细胞的凋亡在早期糖尿病视网膜病变中呈正相关性。
4：JNK2抑制剂的研究有可能成为糖网病早期治疗的一种新方法。
Objective:
Through observing JNK2 to mice in the early course of diabetic retinopathy and changes in the expression of retinal ganglion cells in apoptosis, Discussing JNK2 in diabetic retinopathy (DR) mechanism of the early, and to further explore the pathogenesis of diabetic mechanism and provide theoretical basis for early treatment.
Methods:
C57BL/6 male mice were randomly divided into experimental and control groups, the experimental group were administered intraperitoneally with 1% STZ-induced diabetes model, the control group were injected with doses of sodium citrate buffer, model by made success insist 2,4,8 weeks after operation, taking out eye of the mices and left eye retinal extract for RT-real-time PCR, detection of JNK2 mRNA expression at different times changes in the eye right eye out, HE staining and TUNEL methods, respectively, in the period of retinal morphology and retinal ganglion cell apoptosis.
Results:
(1) JNK2 expression in the retina of DM:The normal group of mice in the expression of no significant difference in diabetic mice 2 weeks with the same expression of normal mice JNK2 was no significant difference (t=-0.109, p= 0.915＞0.05); January group of diabetic mice than the same period in normal JNK2 expression increased (p= 0.002＜0.05); 2 month group were significantly increased expression of JNK2 (p= 0.000＜0.01)
(2) The rate of ganglion cells:ganglion cells of normal mice have a small amount of apoptosis, and no significant difference among the groups, diabetes 2 weeks of ganglion cells was not significant (between groups p= 0.086＞0.05); diabetes 4 weeks, retinal ganglion cell layer of apoptotic cells can be found(between groups p= 0.000＜0.01); diabetes 8 weeks, ganglion cell layer of apoptotic cells increased, inner nuclear layer and outer nuclear layer is also visible apoptotic cells. (between groups p= 0.000＜0.01)
(3) HE staining and ganglion cell counts:normal layered retinal clear, RGCS arranged in neat rows, the inner plexiform layer staining is uniform, inner nuclear layer and outer nuclear layer cells were arranged in order, as the cone cells, rod cells lined; 2 months group and the normal layers of the retina of diabetic mice was no significant change in the experimental group of mice 4 weeks slightly disordered layered retina, normal morphology, but more sparse; DM 2 month group reduce the number of ganglion cells in the more obvious nerve fiber layer and inner plexiform layer of thin, inner nuclear layer cells arranged irregularly, outer plexiform layer is thinning, fuzzy external membrane, rod cell layer disorder. Ganglion cells 2 weeks of diabetes compared with no significant difference between the normal group (between groups p= 0.137＞0.05), diabetes in January the number of ganglion cells in mice began to become less (between groups p= 0.000＞0.05); group two months to further reduce the number of ganglion cells (between groups p= 0.000＞0.05).
Conclusion:
(1) Diabetic retinopathy is a variety of factors, many ways to the complex process of co-regulation.
(2) JNK2 in early diabetic retinopathy may be important regulatory factor, and its expression is closely related with the DM of course.
(3) JNK2 and the expression of retinal ganglion cells apoptosis in nerve cells was positively correlated.
(4) JNK2 inhibitors may be a new method during early treatment of diabetic
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