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目的观察西格列汀对糖尿病肾病(DN)大鼠肾脏的保护作用及对细胞外信号调节激酶1/2(ERK1/2)信号通路的影响。方法 40只雄性Wistar大鼠随机分为正常对照组(NC)、DN模型组(DN)、西格列汀小剂量干预组(ST_1)、西格列汀大剂量干预组(ST_2)。第16周末处死大鼠,检测血糖、HbA_1c、UAER、Scr,肌酐清除率(Ccr)及肾重指数;光镜观察肾组织病理变化;免疫组织化学法及RTPCR检测肾脏足细胞标记蛋白(Podocalyxin)和ERK1/2蛋白及基因的表达。结果(1)16周末,ST_1组、ST_2组与DN组比较,FPG、UAER、Scr、HbA_1c和肾重指数下降(P<0.05),Ccr升高(P<0.05);ST_2组上述变化更明显(P<0.05)。(2)与DN组比较,ST_1组和ST_2组肾小球病理损伤有所改善;且ST_2组较ST_1组改善更明显。(3)与DN组比较,免疫组织化学显示,ST_1组和ST_2组肾小球Podocalyxin的表达增加[(0.235±0.012)vs(0.456±0.024)vs(0.678±0.021),P<0.05];ERK1/2表达降低[(8.021±0.231)vs(6.121±0.021)vs(4.098±0.130),P<0.05],与ST_1组比较,ST_2组上述变化更明显(P<0.01)。RT-PCR检测Podocalyxin和ERK1/2基因表达趋势与免疫组织化学表达一致。结论西格列汀可延缓DN的进展,其机制与抑制ERK1/2信号通路的活化有关。
Objective To observe the protective effect of sitagliptin on the kidney of diabetic nephropathy (DN) rats and its effect on extracellular signal-regulated kinase 1/2 (ERK1 / 2) signaling pathway. Methods Forty male Wistar rats were randomly divided into three groups: normal control group (DN), sitagliptin low dose intervention group (ST_1) and sitagliptin high dose intervention group (ST_2). The rats were killed at the end of the 16th week, and the blood glucose, HbA 1c, UAER, Scr, creatinine clearance (Ccr) and renal gravidity index were detected. The pathological changes of renal tissues were observed by light microscope. Immunohistochemistry and RTPCR were used to detect the expression of podocyte marker protein (Podocalyxin) And ERK1 / 2 protein and gene expression. Results (1) At the end of 16th week, the levels of FPG, UAER, Scr, HbA 1c and the index of renal weight decreased in ST_1 group and ST_2 group compared with those in DN group (P <0.05) (P <0.05). (2) Compared with DN group, glomerular pathological damage was improved in ST_1 group and ST_2 group, and ST_2 group was more obvious than ST_1 group. (3) Compared with DN group, the expression of Podocalyxin in ST_1 group and ST_2 group was significantly higher than that in DN group ([(0.235 ± 0.012) vs (0.456 ± 0.024) vs (0.678 ± 0.021), P <0.05] Compared with ST_1 group, the changes of ST_2 group were more obvious (P <0.01). (2) Compared with ST_1 group, the change of ST_2 group was more obvious (P <0.01). RT-PCR detection of Podocalyxin and ERK1 / 2 gene expression trends consistent with immunohistochemical expression. Conclusion Sogliptin can delay the progression of DN, the mechanism of which is related to the inhibition of the activation of ERK1 / 2 signaling pathway.