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Expression pattern of apoptosis-inducing factor in the kidneys of streptozotocin-induced diabetic rats
Acta Histochemica ( IF 2.5 ) Pub Date : 2020-11-07 , DOI: 10.1016/j.acthis.2020.151655
Sandra Kostic 1 , Tim Hauke 1 , Nasrollah Ghahramani 2 , Natalija Filipovic 1 , Katarina Vukojevic 1
Affiliation  

Background

It is believed that tubulo-interstitial fibrosis and atrophy in diabetic patients are directly associated with the progression of chronic kidney disease, CKD. AIF is one of the crucial factors responsible for mitochondrial apoptosis, however, it can also promote cell survival independently from its role in apoptosis, and therefore can be potentially used as a tool in prevention of the onset of CKD in diabetic patients. Our aim was to investigate the significance of AIF expression in the development of CKD by observing the expression of AIF in 2 weeks’ and 2 months’ kidneys of diabetic rats compared to their controls.

Methods

Male Sprague–Dawley rats were treated with 55 mg/kg streptozotocin (model of type 1 diabetes mellitus; DM group) or citrate buffer (control). After 2 weeks and 2 months kidney samples were collected and analysed in different renal areas.

Results

Characteristic morphologic changes were found between the 2 months’ control and 2 months’ diabetic groups. Those changes, including fibrosis and possible replacement of podocytes with connective tissue were mainly present in the glomeruli. AIF expression was seen in the both cortex, and in the collecting ducts of the medulla. Strong intensity of AIF expression was seen in proximal and distal convoluted tubules in both diabetic groups. In the control groups the glomeruli showed no AIF staining but moderate staining was seen in both diabetic groups. Overall, the percentage of AIF positive cells in the glomeruli was the lowest. The greatest rise in cell positivity was displayed from the 2 weeks’ control group to 2 weeks’ diabetes group (38 %) in glomeruli. The cell positivity of the 2 weeks’ diabetic group is significantly reduced to 18 % in the 2 months’ diabetic group in glomeruli. A similar pattern was seen in the proximal tubular cells (92 % positivity 2 weeks diabetic groups; 89 % positivity 2 months diabetic groups), as well as in the distal tubules. The highest percentage of AIF positive cells was seen in the collecting ducts, more than 80 % in all groups.

Conclusions

Our study provides insight into AIF expression pattern during short term diabetes model, confirming possible dual role of AIF, not only in apoptosis but also in cell function and homeostasis, and proving AIF as potential therapeutic target and marker of advancement of CKD.



中文翻译:

链脲佐菌素致糖尿病大鼠肾脏凋亡诱导因子的表达模式

背景

人们认为糖尿病患者的肾小管间质纤维化和萎缩与慢性肾病 CKD 的进展直接相关。AIF 是导致线粒体凋亡的关键因素之一,然而,它也可以独立于其在细胞凋亡中的作用而促进细胞存活,因此有可能用作预防糖尿病患者 CKD 发作的工具。我们的目的是通过观察糖尿病大鼠 2 周和 2 个月肾脏中 AIF 的表达与其对照相比,研究 AIF 表达在 CKD 发展中的意义。

方法

雄性 Sprague-Dawley 大鼠用 55 mg/kg 链脲佐菌素(1 型糖尿病模型;DM 组)或柠檬酸盐缓冲液(对照)治疗。2 周和 2 个月后,在不同的肾脏区域收集和分析肾脏样本。

结果

在 2 个月的对照组和 2 个月的糖尿病组之间发现了特征性的形态学变化。这些变化,包括纤维化和可能的结缔组织替代足细胞,主要存在于肾小球中。在两个皮质和髓质集合管中都观察到 AIF 表达。在两个糖尿病组的近端和远端回旋小管中都观察到 AIF 表达的强强度。在对照组中,肾小球未显示 AIF 染色,但在两个糖尿病组中均可见中等染色。总体而言,肾小球中 AIF 阳性细胞的百分比最低。从 2 周的对照组到 2 周的糖尿病组 (38 %),肾小球中细胞阳性率的上升幅度最大。2周糖尿病组的肾小球细胞阳性率显着降低至2个月糖尿病组的18%。在近端肾小管细胞(92% 阳性 2 周糖尿病组;89% 阳性 2 个月糖尿病组)以及远端肾小管细胞中观察到类似的模式。在集合管中观察到 AIF 阳性细胞的百分比最高,在所有组中都超过 80%。

结论

我们的研究提供了对短期糖尿病模型中 AIF 表达模式的洞察,证实了 AIF 可能的双重作用,不仅在细胞凋亡中,而且在细胞功能和体内平衡中,并证明 AIF 是潜在的治疗靶点和 CKD 进展的标志物。

更新日期:2020-11-09
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