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药根碱对糖尿病模型大鼠血管Akt/AMPK/eNOS信号通路的影响

Effects of Jatrorrhizine on Akt/AMPK/eNOS Signaling Pathways in Blood Vessel of Diabetes Rats

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【作者】 王云山张洪张晓春

【Author】 WANG Yunshan;ZHANG Hong;ZHANG Xiaochun;Department of Pharmacy,Suizhou Hospital,Hubei University of Medicine;Department of Pharmacy,Renmin Hospital of Wuhan University;

【机构】 湖北医药学院附属随州医院药剂科武汉大学人民医院药学部

【摘要】 目的观察药根碱对糖尿病大鼠血管蛋白激酶B/一磷酸腺苷活化蛋白激酶/内皮型一氧化氮合酶(Akt/AMPK/e NOS)信号通路的影响及对糖尿病大鼠可能的保护作用机制。方法将60只雄性Wistar大鼠随机分为正常对照组、模型对照组、药根碱小剂量组和大剂量组,除正常对照组外,其他组通过诱导胰岛素抵抗后空腹腹腔注射链脲佐菌素制作2型糖尿病模型,正常对照组和模型对照组大鼠每日灌胃5%羧甲基纤维素钠溶液,药根碱大剂量组和小剂量组每日分别给予药根碱100,50 mg·kg-1,连续8周。检测各组大鼠体质量、血糖及血清胰岛素水平,酶联免疫吸附测定(ELISA)法比较各组大鼠血清中炎症因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平,Western blotting法检测各组大鼠血管中e NOS蛋白及Akt/AMPK通路蛋白的表达。结果与正常对照组比较,模型对照组大鼠体质量下降,血糖升高,血清胰岛素水平显著性升高,差异有统计学意义(P<0.01);与模型对照组比较,药根碱大剂量组体质量显著增加,血糖降低,胰岛素水平下降均差异有统计学意义(P<0.01)。正常对照组血清中IL-1β为(92.3±4.3)pg·mL-1,模型对照组为(152.4±20.0)pg·mL-1,药根碱小剂量组和大剂量组分别为(120.96±33.0),(95.05±7.7)pg·mL-1;模型对照组血清中TNF-α为(10.50±0.82)pg·mL-1,正常对照组为(7.48±0.36)pg·mL-1,药根碱小剂量组和大剂量组TNF-α分别为(8.82±0.42)和(7.11±0.33)pg·mL-1;与正常对照组比较,模型对照组大鼠血管中e NOS表达量及磷酸化的Akt和AMPK含量显著减少,药根碱大剂量组较模型对照组显著提高(P<0.05或P<0.01)。结论药根碱可能通过影响糖尿病大鼠血管中Akt/AMPK/e NOS信号通路及对抗炎症作用对糖尿病大鼠具有保护作用。

【Abstract】 Objective To observe the influence of jatrorrhizine on the Akt/AMPK/e NOS signaling pathways and potential protective function in blood vessel of diabetes rats. Methods Male Wistar rats( n = 60) were randomly divided into normal control group,model control group,low-and high dose jatrorrhizine groups. Except normal control group,the other rats were given intraperitoneal injection of STZ after induced insulin resistance,to made type Ⅱdiabetes model. CMC-Na solution( 5%) was given to normal control and model control group, and the jatrorrhizine resolved in the same solution was administered to low( 50 mg·kg-1) and high dose( 100 mg·kg-1) jatrorrhizine groups for 8 weeks. Their body weight,blood glucose,and serum insulin levels were measured at the end of the treatment,IL-1β,TNF-α level in serum were measured by ELISA,and the e NOS,Akt/AMPK protein expression levels in the blood vessel were measured by Western blotting. Results Compared with normal control group,the weight of model control group was lossed,blood glucose was increased( P<0.01). Compared with model control group,high-dose jatrorrhizine significantly increased body weight,alleviated blood glucose and decreased serum insulin( P<0.01).Serum inflammatory factor like IL-1β was( 92.3±4.3) pg·mL-1 in normal control group,( 152.4±20.0) pg·mL-1 in model control group,( 120.96±33.0) pg·mL-1 and( 95.05±7.7) pg·mL-1 in low-and high-dose jatrorrhizine groups,respectively. TNF-α was( 10.50±0.82) pg·mL-1 in model control group,( 7.48±0.36) pg·mL-1 in normal control group,( 8.82±0.42) and( 7.11±0.33)pg· mL-1 in low-and high-dose jatrorrhizine groups,respectively. As compared with control group,e NOS and Akt/AMPK expression in blood vessel was significantly reduced( P < 0. 05) in model control group,and those were significantly increased in high-dose jatrorrhizine group as compared with model control group( P<0.05 or P<0.01). Conclusion Jatrorrhizine may exert protective effect on diabetes mellitus rats through regulating Akt/AMPK/e NOS signaling pathway in blood vessel.

  • 【文献出处】 医药导报 ,Herald of Medicine , 编辑部邮箱 ,2017年10期
  • 【分类号】R285.5;R-332
  • 【被引频次】7
  • 【下载频次】232
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