【摘要】 目的观察沙格列汀治疗老年糖尿病肾病对外周血TNF-α、IL-1和IL-6水平以及外周血单核细胞PI3K、Akt的磷酸化水平的影响。方法选取许昌市中心医院60例早期老年糖尿病肾病患者,比较治疗前后对照组和实验组各项指标变化。另外,沙格列汀治疗8周后观察临床各项指标包括空腹血糖、糖化血红蛋白(Hb A1 c)、24 h尿白蛋白量(24 h UPro)和血肌酐(Cr),以及血浆中TNF-α、IL-6和IL-1水平。同时,检测外周血提取的单核细胞的PI3K和Akt的磷酸化水平。结果与对照组相比,实验组外周血清空腹血糖水平显著下降(P<0.05),同时Hb A1 c显著下降(P<0.05),24 h UPro显著下降(P<0.05),血肌酐(Cr)水平显著降低(P<0.05);另外,与对照组相比,实验组患者血浆中炎症因子TNF-α、IL-6和IL-β的表达水平显著降低(P<0.05);与对照组相比,实验组的外周血提取的单核细胞中PI3K的磷酸化水平和Akt表达水平也显著升高(P<0.05)。结论沙格列汀治疗老年糖尿病肾病患者可显著降低Hb A1 c、24 h UPro和Cr,进而改善肾功能,同时可降低外周血TNF-α、IL-6和IL-1β水平,缓解外周炎症免疫反应,并显著上调外周血单核细胞的PI3K和Akt磷酸化水平。沙格列汀在改善外周血高血糖状态时,进一步恢复PI3K/Akt磷酸化活化水平,参与抑制炎症反应。更多还原

【Abstract】 This study was designed to investigate the effects of saxagliptin on peripheral blood TNF-α, IL-1 and IL-6 levels as well as the phosphorylation levels of PI3 K-Akt in peripheral blood mononuclear cells of elderly diabetic nephropathy patients. Total of 60 cases of early senile diabetic nephropathy was recruited from Xuchang Central Hospital, and divided randomly into control and experiment groups. The clinical indices of the control group and the experimental group were compared before and after treatment. In addition, after 8 weeks of saxagliptin treatment, we observed the clinical indicators including fasting blood glucose, glycosylated hemoglobin(Hb A1 C), 24 hour urine protein(24 h UPro), serum creatinine(Cr), and the levels of TNF-α, IL-6 and IL-1β in plasma. Furthermore, PI3 K and Akt phosphorylation levels of monocytes extracted from peripheral blood were tested by Western blot. Data showed that the serum fasting blood glucose, Hb A1 c, 24 h UPro, serum creatinine(Cr)levels, and the levels of plasma TNF-α, IL-1β and IL-6 of experimental group decreased significantly,as compared with control group(P<0.05). The levels of PI3 K phosphorylation and Akt expression in monocytes the experimental group were significantly increased compared with the control group(P<0.05). Taken together,treatment of combined saxagliptin can reduce Hb A1 C, 24 h UPro, Cr, and the levels of TNF-α, IL-6 and IL-1β in peripheral blood, thus relieve the peripheral inflammatory responses in elderly patients. Meanwhile, saxagliptin also up-regulates the levels PI3 K and Akt phosphorylation of monocytes from peripheral blood. Saxagliptin improves the level of PI3 K/Akt phosphorylation and participates in the inhibition of inflammatory response by improving the peripheral blood glucose status.更多还原