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长链非编码 RNA(lncRNA)SNHG5 通过调节 TGR5 参与袖状胃切除术治疗 II 型糖尿病。

Long Non-Coding RNA (lncRNA) SNHG5 Participates in Vertical Sleeve Gastrectomy for Type II Diabetes Mellitus by Regulating TGR5.

机构信息

Department of General Surgery, First Affiliated Hospital of JiaMusi University, Jiamusi, Heilongjiang, China (mainland).

Department of Radiology, First Affiliated Hospital of JiaMusi University, Jiamusi, Heilongjiang, China (mainland).

出版信息

Med Sci Monit. 2020 Apr 3;26:e920628. doi: 10.12659/MSM.920628.

Abstract

BACKGROUND Due to its remarkable effect in controlling glycometabolism, relatively simple operation, and low risk of complications, sleeve gastrectomy (SG) has become the preferred surgical treatment for type II diabetes mellitus. Increased blood glucose in the body can cause damage to functional cells. MATERIAL AND METHODS Long non-coding RNA SNHG5 expression and TGR5 in serum were analyzed by real-time PCR. A diabetic cell model was established by culturing normal human intestinal epithelial cells NCM460 and DLD-1 with high-glucose and high-fat medium. CCK-8 assay, TUNEL assay, and flow cytometry were used to assess cell growth and apoptosis, respectively. The secretion of lactate dehydrogenase (LDH) was detected using the LDH Cytotoxicity Kit. lncRNA SNHG5 was downregulated by siRNA. The changes in expression of SNHG5, TGR5, Akt, p65, and Bcl-2 were analyzed by real-time PCR assay or Western blot. RESULTS In 40 type II diabetes patients who underwent sleeve gastrectomy, the expression of SNHG5 decreased and the expression of TGR5 increased compared with that before the operation. After high-glucose and high-fat culture, cell growth was inhibited and cell apoptosis increased significantly. The expression of SNHG5 was increased and TGR5 was decreased with high-glucose and high-fat culture. However, high glucose and high fat showed an opposite trend for cell growth, apoptosis, and LDH release under inhibition of SNHG5. The expression levels of TGR5 and Akt, p65, and Bcl-2 were also returned to normal by SNHG5 inhibition. CONCLUSIONS By downregulating expression of the SNHG5 gene and then altering expression of the TGR5 gene, the damage to colorectal cells induced by high glucose was alleviated. This may be one of the mechanisms underlying the effect of sleeve gastric surgery in treatment of diabetes mellitus.

摘要

背景

由于袖状胃切除术(SG)在控制糖代谢方面效果显著、操作相对简单、并发症风险低,已成为治疗 2 型糖尿病的首选手术方法。体内血糖升高会导致功能性细胞受损。

方法

采用实时 PCR 分析血清中长链非编码 RNA SNHG5 的表达和 TGR5。用高糖高脂培养基培养正常的人肠上皮细胞 NCM460 和 DLD-1,建立糖尿病细胞模型。CCK-8 测定法、TUNEL 测定法和流式细胞术分别用于评估细胞生长和细胞凋亡。用乳酸脱氢酶(LDH)细胞毒性试剂盒检测 LDH 的分泌。用 siRNA 下调 lncRNA SNHG5。通过实时 PCR 测定或 Western blot 分析 SNHG5、TGR5、Akt、p65 和 Bcl-2 的表达变化。

结果

在 40 例行袖状胃切除术的 2 型糖尿病患者中,与手术前相比,SNHG5 的表达降低,TGR5 的表达升高。经高糖高脂培养后,细胞生长受到抑制,细胞凋亡明显增加。高糖高脂培养后 SNHG5 表达增加,TGR5 表达减少。然而,在抑制 SNHG5 后,细胞生长、凋亡和 LDH 释放的高糖和高脂表现出相反的趋势。TGR5 和 Akt、p65、Bcl-2 的表达水平也通过 SNHG5 抑制恢复正常。

结论

通过下调 SNHG5 基因的表达,然后改变 TGR5 基因的表达,减轻了高葡萄糖对结直肠细胞的损伤。这可能是袖状胃切除术治疗糖尿病的作用机制之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8d/7154564/fb57e139c4b4/medscimonit-26-e920628-g001.jpg

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