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没食子酸表没食子儿茶素酯通过调节链脲佐菌素-烟酰胺诱导的糖尿病大鼠的心脏代谢危险因素、氧化应激、炎症、细胞死亡和纤维化,来预防糖尿病心肌病。

Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats.

机构信息

Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.

Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.

出版信息

Biomed Pharmacother. 2017 Oct;94:362-373. doi: 10.1016/j.biopha.2017.07.129. Epub 2017 Aug 1.

Abstract

The potential protective effect of epigallocatechin-3-gallate (EGCG) on type 2 diabetes-induced heart injury was investigated. A rat model of diabetes was achieved by injection of nicotinamide (100mg/kg, i.p), 20min before the administration of streptozotocin (55mg/kg, i.p.). After confirmation of diabetes, EGCG (2mg/kg, p.o.) was administrated on alternate days for one month. Treatment of diabetic rats with EGCG showed a remarkable reduction in glucose, glycosylated hemoglobin, HOMA-IR and lipid profile levels with an elevation in insulin levels, indicating its antihyperglycemic and antidyslipidemic actions. EGCG treatment also suppressed the increase in the levels of superoxide, 4-hydroxynonenal and protein carbonyl, whereas it increased the content of glutathione and the activities of superoxide dismutase and catalase in heart of diabetic rats, indicating its antioxidant capacity. In addition, EGCG improved heart function of diabetic rats as evidenced by a remarkable reduction in troponin T level and creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase activities in the serum. Oral administration of EGCG for one month after diabetes induction significantly protected the increase in serum levels of pro-inflammatory cytokines (IL-1 β, IL-6 and TNF-α) and adhesion molecules (ICAM-1 and VCAM-1), suggesting its anti-inflammatory potential. Furthermore, EGCG hampered the mitochondrial apoptotic pathway through increasing Bcl-2 level and decreasing p53, Bax, cytochrome c and caspase-3 and 9 levels in hearts of diabetic rats, indicating its anti-apoptotic action. Diabetic rats treated with EGCG also exhibited decreased level of DNA damage in the myocardium. The histological examinations indicated the cardioprotective effect of EGCG against harmful impact of diabetes. Therefore, these findings suggest that EGCG has a protective effect on the heart affected by type 2 diabetes and recommend it as a complementary supplement for diabetic patients.

摘要

探讨了表没食子儿茶素没食子酸酯(EGCG)对 2 型糖尿病诱导的心脏损伤的潜在保护作用。通过注射烟酰胺(100mg/kg,腹腔注射),在给予链脲佐菌素(55mg/kg,腹腔注射)前 20 分钟,建立糖尿病大鼠模型。确认糖尿病后,EGCG(2mg/kg,口服)隔日给药 1 个月。用 EGCG 治疗糖尿病大鼠可显著降低血糖、糖化血红蛋白、HOMA-IR 和血脂谱水平,同时升高胰岛素水平,表明其具有抗高血糖和抗脂解作用。EGCG 治疗还抑制了超氧化物、4-羟壬烯醛和蛋白羰基水平的升高,同时增加了谷胱甘肽的含量和超氧化物歧化酶和过氧化氢酶的活性,表明其具有抗氧化能力。此外,EGCG 改善了糖尿病大鼠的心脏功能,表现为血清肌钙蛋白 T 水平和肌酸激酶-MB、乳酸脱氢酶和天冬氨酸氨基转移酶活性显著降低。糖尿病诱导后口服 EGCG 1 个月可显著保护血清中促炎细胞因子(IL-1β、IL-6 和 TNF-α)和黏附分子(ICAM-1 和 VCAM-1)水平的升高,表明其具有抗炎潜力。此外,EGCG 通过增加糖尿病大鼠心脏中 Bcl-2 水平和降低 p53、Bax、细胞色素 c 和 caspase-3 和 9 水平,阻止了线粒体凋亡途径,表明其具有抗凋亡作用。用 EGCG 治疗的糖尿病大鼠心肌的 DNA 损伤水平也降低。组织学检查表明 EGCG 对糖尿病有害影响具有心脏保护作用。因此,这些发现表明 EGCG 对 2 型糖尿病引起的心脏具有保护作用,并推荐其作为糖尿病患者的补充补充剂。

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