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袖状胃切除术通过改善糖尿病肥胖大鼠的氧化应激状态来改善糖尿病相关的脾脏损伤。

Sleeve Gastrectomy Ameliorates Diabetes-Related Spleen Damage by Improving Oxidative Stress Status in Diabetic Obese Rats.

机构信息

Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766#, Jingshi Road, Jinan, Shandong Province, 250014, People's Republic of China.

Shandong Medical College, Jucai 6# Road, Linyi, Shandong Province, 276000, People's Republic of China.

出版信息

Obes Surg. 2021 Mar;31(3):1183-1195. doi: 10.1007/s11695-020-05073-3. Epub 2020 Oct 26.

Abstract

PURPOSE

Oxidative stress and inflammation are important pathogenic mediators in diabetes-related organ damage. Accumulating evidence suggests that immunodeficiency in diabetes is associated with diabetes-induced spleen damage. Sleeve gastrectomy (SG) has been proved to improve diabetes and its multiple associated complications. However, the ameliorative role of SG against spleen damage in diabetes has not been investigated.

MATERIALS AND METHODS

Animal model of diabetic obese rats induced by high-fat diet (HFD) combined with streptozotocin (STZ) was treated with sham operation, caloric restriction, and SG. Metabolic parameters were measured, and the morphological and histopathological changes, status of oxidative stress, and levels of inflammatory factors were evaluated.

RESULTS

SG reduced body weight and improved glucose tolerance and insulin sensitivity in diabetic obese rats. SG significantly reversed splenic atrophy and alleviated abnormalities of white and red pulp. Additionally, SG also reversed the increased splenocyte apoptosis (P < 0.001). Meanwhile, indicators of oxidative stress including reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and protein carbonylation were reduced, and the activity and expression of antioxidant enzymes including SOD and CAT were improved after SG. The mRNA expression of inflammatory factors in SG groups such as TNF-α (P < 0.001), IL-6 (P < 0.001), MCP-1 (P < 0.01), and ICAM-1 (P < 0.001) was also significantly reduced.

CONCLUSION

SG ameliorates diabetes-related splenic injury by restoring the balance between oxidative stress process and antioxidant defense systems as well as reducing inflammation in the spleen. These findings indicate that SG is an appropriate therapeutic strategy for diabetes-related spleen damage.

摘要

目的

氧化应激和炎症是糖尿病相关器官损伤的重要发病机制。越来越多的证据表明,糖尿病患者的免疫缺陷与糖尿病引起的脾脏损伤有关。袖状胃切除术(SG)已被证明可改善糖尿病及其多种相关并发症。然而,SG 对糖尿病脾损伤的改善作用尚未得到研究。

材料和方法

采用高脂肪饮食(HFD)联合链脲佐菌素(STZ)诱导的糖尿病肥胖大鼠动物模型,分别进行假手术、热量限制和 SG 治疗。测量代谢参数,并评估形态和组织病理学变化、氧化应激状态和炎症因子水平。

结果

SG 可降低糖尿病肥胖大鼠的体重,改善葡萄糖耐量和胰岛素敏感性。SG 可显著逆转脾脏萎缩,减轻白髓和红髓的异常。此外,SG 还逆转了脾细胞凋亡的增加(P<0.001)。同时,SG 还降低了活性氧(ROS)、一氧化氮(NO)、丙二醛(MDA)和蛋白质羰基化等氧化应激指标,提高了超氧化物歧化酶(SOD)和过氧化氢酶(CAT)等抗氧化酶的活性和表达。SG 组促炎因子 TNF-α(P<0.001)、IL-6(P<0.001)、MCP-1(P<0.01)和 ICAM-1(P<0.001)的 mRNA 表达也明显降低。

结论

SG 通过恢复氧化应激过程与抗氧化防御系统之间的平衡以及减轻脾脏炎症来改善糖尿病相关的脾脏损伤。这些发现表明 SG 是治疗糖尿病相关脾脏损伤的一种合适的治疗策略。

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