Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mol Med Rep. 2020 Sep;22(3):1892-1900. doi: 10.3892/mmr.2020.11270. Epub 2020 Jun 24.
Numerous studies have reported that diabetes is associated with an increased susceptibility to cardiac ischemia‑ reperfusion injury; however, the mechanism underlying the role of diabetes during intestinal ischemia‑reperfusion (IIR) has yet to be elucidated. The present study evaluated the intestinal pathological alterations and possible underlying mechanisms in a mouse model of type 1 diabetes mellitus with IIR. The effects of diabetes were investigated by assessing the histopathology, oxidative stress, inflammatory cytokine levels in intestine tissues and blood plasma, and protein expression levels of phosphatase and tensin homolog‑induced putative kinase (PINK1), Parkin and the ratio of light chain 3B (LC3B) II/I. The results demonstrated that diabetes increased the Chiu's intestinal injury score, concentration of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α, and levels of oxidative stress. Furthermore, the alterations were more pronounced in the diabetes with IIR group. The expression levels of PINK1 and Parkin, as well as the ratio of LC3BII/I, were significantly upregulated in the IIR group compared with the Sham group. Diabetes activated PINK1 and Parkin, and increased the expression of LC3BII. Furthermore, transmission electron microscopy revealed that mitochondrial destruction and the number of autophagosomes was increased in the diabetic groups compared with the non‑diabetic groups. Collectively, the results of the present study suggest that diabetes increased intestinal vulnerability to IIR by enhancing inflammation and oxidative stress. Furthermore, IIR was associated with overactivation of mitochondrial autophagy; therefore, the increased vulnerability to IIR‑induced intestine damage due to diabetes may be associated with PINK1/Parkin‑regulated mitochondrial autophagy.
大量研究报道称，糖尿病与心脏缺血再灌注损伤的易感性增加有关；然而，糖尿病在肠缺血再灌注（IIR）中作用的机制尚不清楚。本研究评估了 1 型糖尿病小鼠模型中 IIR 时的肠道病理改变及可能的机制。通过评估组织病理学、氧化应激、肠道组织和血浆中炎症细胞因子水平以及磷酸酶和张力蛋白同源物诱导的假定激酶（PINK1）、Parkin 和轻链 3B（LC3B）II/I 的蛋白表达水平，研究了糖尿病的影响。结果表明，糖尿病增加了 Chiu 肠损伤评分、白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α的浓度以及氧化应激水平。此外，在糖尿病伴 IIR 组中这些改变更为明显。与 Sham 组相比，IR 组的 PINK1 和 Parkin 表达水平以及 LC3BII/I 比值显著上调。糖尿病激活了 PINK1 和 Parkin，并增加了 LC3BII 的表达。此外，透射电子显微镜显示，与非糖尿病组相比，糖尿病组的线粒体破坏和自噬体数量增加。综上所述，本研究结果表明，糖尿病通过增强炎症和氧化应激增加了肠道对 IIR 的易感性。此外，IIR 与线粒体自噬的过度激活有关；因此，糖尿病导致的 IIR 诱导的肠道损伤的易感性增加可能与 PINK1/Parkin 调节的线粒体自噬有关。
