| 郭芬,王晓雪.柚皮苷调控 PI3K/Akt/eNOS通路控制 2型糖尿病大鼠脑血管内皮氧化损伤的作用探讨[J].安徽医药,2021,25(4):645-649. |
| 柚皮苷调控 PI3K/Akt/eNOS通路控制 2型糖尿病大鼠脑血管内皮氧化损伤的作用探讨 |
| Naringin regulates PI3K / Akt / eNOS pathway to control cerebral vascular endothelial oxida? tive damage in type 2 diabetic rats |
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| DOI：10.3969/j.issn.1009-6469.2021.04.003 |
| 中文关键词: 葡萄柚 糖尿病， 2型 柚皮苷 PI3K/Akt/eNOS信号通路 血管内皮 氧化损伤 大鼠， Sprague-Dawley |
| 英文关键词: Citrus paradisi Diabetes mellitus, type 2 Naringin PI3K / Akt / eNOS signaling pathway um Oxidative damage Rats, Sprague-Dawley |
| 基金项目:河南省医学科技攻关计划项目名称(201702133) |
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| 中文摘要: |
| 目的探讨柚皮苷对 2型糖尿病大鼠脑血管内皮氧化损伤的治疗效果，以及柚皮苷对 3-磷酸肌醇激酶(PI3K)/蛋白激酶 B(AKT)/内皮型一氧化氮(eNOS)信号通路的调控作用。方法 2019年 3月 15日至 2020年 5月 20日，将 SD大鼠(南京医科大学实验动物中心)按随机字母表法分为 4组，对照组大鼠给予标准饲料，其他组给予高糖高脂饲料。通过腹腔注射 60 mg/kg的链脲佐菌素(STZ)建立 2型糖尿病模型，柚皮苷组大鼠灌胃 100 mg/kg的柚皮苷溶液，柚皮苷 +LY294002组大鼠在灌胃 100 mg/kg的柚皮苷溶液的基础上腹腔注射 100 mg/kg的 PI3K抑制剂 LY294002。治疗 8周后，分别检测各组大鼠空腹血糖、一氧化(NO)、血脂代谢指标［总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)］、脑组织氮中丙二醛(MDA)和超氧化物歧化酶(SOD)水平。苏木精 -伊红(HE)染色评价脑组织病理改变。蛋白质印迹法(Western blotting)检测脑组织中 PI3K/Akt/eNOS通路的活化情况。结果柚皮苷组的空腹血糖(13.46±1.09)mmol/L、TC(1.65±0.13)mmol/L、 TG(2.89±0.23)mmol/L、LDL-C(1.59±0.13)mmol/L、MDA(55.17±4.24)U/mgprot水平均低于模型组［空腹血糖(25.32±2.04)mmol/ L、TC(2.81±0.23)mmol/L、TG(4.36±0.35)mmol/L、LDL-C(2.97±0.24)mmol/L、MDA(9.37±0.72)nmol/mgprot］，而 HDL-C(1.08±0.08)mmol/L、血清 NO(28.76±2.21)μmol/L、SOD(55.17±4.24)U/mgprot水平均高于模型组［HDL-C(0.65±0.05)mmol/L、血清 NO(19.11±1.47)μmol/L、SOD(41.22±3.17)U/mgprot］(P<0.05)。柚皮苷组的 PI3K蛋白表达水平(0.81±0.06)及 Akt(0.91±0.07)和 eNOS(0.97±0.07)的磷酸化水平均高于模型组［PI3K蛋白表达水平(0.31±0.02)、(0.21±0.02)和 eNOS(0.18±0.01)］(P<0.05)。此外， LY294002处理可显著减弱柚皮苷对上述指标的影响(P<0.05)。结论柚皮苷对 2型糖尿病大鼠的脑保护作用主要由 PI3K/AKT/eNOS信号通路介导。 |
| 英文摘要: |
| Objective To explore the therapeutic effect of naringin on cerebral vascular endothelial oxidative damage in type 2 diabetic rats, and the regulating effect of naringin on 3-phosphoinositide kinase (PI3K) / protein kinase B (AKT) / endothelial nitric oxide (eNOS) signaling pathway.Methods From March 15, 2019 to May 20, 2020, SD rats (Experimental Animal Center of Nanjing MedicalUniversity) were assigned into 4 groups according to the random alphabet method. Normal control rats were fed with standard feed, andother groups were fed with high-sugar and high-fat feed. A model of type 2 diabetes was established by intraperitoneal injection of 60mg/kg streptozotocin (STZ). Rats in the naringin group were administrated with a 100 mg/kg naringin solution. Rats in the naringin +LY294002 group were intraperitoneally injected with a 100 mg/kg PI3K inhibitor LY294002 on the basis of a 100 mg/kg naringin solution. After 8 weeks of treatment, fasting blood glucose, nitric oxide (NO), lipid metabolism indicators [total cholesterol (TC), triglyceride(TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)], malondialdehyde (MDA), and superoxide dismutase (SOD) levels in brain tissues were measured in each group. Hematoxylin-eosin (HE) staining was used to evaluatethe pathological changes of brain tissues. Western blotting was used to detect the activation of PI3K/Akt/eNOS pathway in brain tissues.Results Fasting blood glucose (13.46±1.09) mmol/L, TC (1.65±0.13) mmol/L, TG (2.89±0.23) mmol/L, LDL-C (1.59±0.13) mmol/L,MDA (55.17±4.24) U/mgprot levels in naringin group were lower than those in the model group [fasting blood glucose, (25.32±2.04)mmol/L; TC, (2.81±0.23) mmol/L; TG, (4.36±0.35) mmol/L; LDL-C, (2.97±0.24) mmol/L; MDA, (9.37±0.72) nmol/mgprot], while HDLC (1.08±0.08) mmol/L, serum NO (28.76±2.21) μmol/L, SOD (55.17±4.24) U/mgprot levels were higher in the naringin group than in the model group [HDL-C, (0.65±0.05) mmol/L; serum NO, (19.11±1.47) μmol/L; SOD, (41.22±3.17) U/mgprot] (P<0.05). The PI3K protein expression level (0.81±0.06) and the phosphorylation levels of Akt (0.91±0.07) and eNOS (0.97±0.07) in the naringin group werehigher than those in the model group [PI3K, (0.31±0.02); Akt, (0.21±0.02); eNOS, (0.18±0.01)] (P<0.05). Additionally, LY294002 treatment significantly reduced the effect of naringin on the above indicators (P<0.05).Conclusion on type 2 diabetic rats is mainly mediated by the PI3K / AKT / eNOS signaling pathway. |
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