活性维生素D对2型糖尿病大鼠肾组织胰岛素信号通路PI3K/Akt的影响

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目的探讨活性维生素D对2型糖尿病大鼠肾组织胰岛素相关信号分子胰岛素受体(IRβ)、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt/PKB)表达的影响。方法 30只雄性Wistar大鼠随机分为普通饲料组即正常组(N组,n=10)和高脂高糖饲料组(n=20),高脂高糖饲料组以小剂量(30 mg/kg)链脲佐菌素(STZ)加高糖高脂饮食诱导2型糖尿病模型后随机分为2组,分别经腹腔注射2.5μg/(kg·d)花生油即糖尿病组(M组,n=10)或腹腔注射2.5μg/(kg·d)溶于花生油中的活性维生素D即维生素D治疗组(D组,n=10)。8周后留取大鼠血标本,测定血糖、血肌酐及尿素氮,处死大鼠留取肾组织。Western blot检测肾组织中胰岛素相关信号分子IRβ、PI3K、Akt的表达及其磷酸化的水平。结果糖尿病组大鼠血糖、尿素氮、肌酐高于正常组(P<0.05);而相对于糖尿病组,维生素D干预组血糖、尿素氮及肌酐明显降低(P<0.05)。Western blot显示相较于正常组,糖尿病组大鼠肾组织总的IRβ、Akt的表达无明显改变而其磷酸化水平及PI3K的水平明显下调,而维生素D干预后明显上调(P<0.05)。结论活性维生素D可激活胰岛素信号通路PI3K/Akt的表达,对糖尿病大鼠肾脏损伤发挥保护作用。 Objective To investigate the effects of active vitamin D on the expression of insulin-like receptor (IRβ), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt / PKB) in kidney of type 2 diabetic rats. Methods Thirty male Wistar rats were randomly divided into two groups: normal group (n = 10) and high fat group (n = 20) kg). STZ plus high glucose and high fat diet induced type 2 diabetes mellitus rats were randomly divided into 2 groups, and were given intraperitoneal injection of 2.5μg / (kg · d) peanut oil, diabetic group (M group, n = 10) or intraperitoneal injection of 2.5μg / (kg · d) of active vitamin D dissolved in peanut oil or vitamin D treatment group (D group, n = 10). After 8 weeks, blood samples of rats were collected, blood glucose, serum creatinine and urea nitrogen were measured, and rats were sacrificed. Western blot was used to detect the expression of insulin-related signal molecules IRβ, PI3K, Akt and their phosphorylation in renal tissues. Results The blood glucose, urea nitrogen and creatinine in diabetic rats were significantly higher than those in normal rats (P <0.05). Compared with those in diabetic rats, the levels of blood glucose, urea nitrogen and creatinine were significantly decreased in vitamin D intervention group (P <0.05). Western blot showed that compared with the normal group, the expression of total IRβ and Akt in the kidney of diabetic rats was not significantly changed, whereas phosphorylation and PI3K levels were significantly decreased in diabetic rats (P <0.05). Conclusion Active vitamin D can activate the expression of PI3K / Akt in insulin signaling pathway and play a protective role in kidney injury in diabetic rats.
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