摘要
目的研究二肽基肽酶4(DPP-4)抑制剂沙格列汀对2型糖尿病大鼠肾脏损伤的保护作用并探讨其作用机制。方法将30只雄性SD大鼠,随机分成3组(每组10只):正常对照组(NC组)、2型糖尿病模型组(T2DM组)、模型+沙格列汀1.0 mg/kg治疗组(Sax组)。NC组大鼠饲以普通饲料;T2DM组及Sax组大鼠以高脂饮食联合链脲佐菌素(STZ)造2型糖尿病大鼠模型;Sax组大鼠每日1次灌胃给予沙格列汀1.0 mg/kg,NC组和T2DM组灌胃给予等容量生理盐水,连续给药12周后实验终止。记录大鼠体重,测定24 h摄食量、饮水量和24 h尿量;检测空腹血糖(GLU),血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、血肌酐(Cr)和血尿素氮(BUN)水平;采用流式细胞术检测外周血T淋巴细胞亚群水平;取肾脏组织行HE染色观察肾组织病理学变化,免疫组化检测肾组织转化生长因子β(TFG-β)的表达水平;Western blot检测肾组织NF-κB p65、COX-2的蛋白表达水平,RT-PCR检测TNF-α、IL-6、Fox O1的mRNA表达水平。结果 Sax组与T2DM组大鼠相比,GLU、TG、TC和LDL水平明显降低(P<0.05),HDL水平明显升高(P<0.05);大鼠饮水量、体重明显降低(P<0.05);Sax组较T2DM模型组大鼠肾小球肿胀、炎性浸润现象明显缓解,TFG-β表达水平降低(P<0.05);外周血T淋巴细胞亚群水平的失衡明显改善(P<0.05);下调炎症相关因子TNF-α、IL-6、Fox O1的mRNA表达水平及NF-κB p65、COX-2的蛋白表达水平(P<0.05)。结论 DPP-4抑制剂沙格列汀具有保护大鼠2型糖尿病肾损害作用,其作用机制可能为抑制炎症的发生及参与免疫调节。
Objective To investigate the effects of Saxagliptin, tes mellitus rats. Methods Thirty male Sprague - Dawley rats a DPP -4 inhibitor, against kidney injury in type 2 diabewere divided into 3 groups randomly （n = 10 ） ： control group, type 2 diabetes mellitus （T2DM） group, T2DM ＋ Saxagliptin 1.0 mg/kg （Sax） group. The rats of T2DM group and Sax group were fed with a high -fat diet and given STZ to establish experimental type 2 diabetes model, while the rats of control group were fed with a normal diet. The rats of Sax grouD were administered Saxagliptin 1.0 mg/kg once a day for 12 weeks and the rats of control group and T2DM group were given equal volume of saline. Blood glucose was measured in a blood glucose meter. TC, TG, LDL, HDL, Cr, BUN were measured in a blood automatic analyzer. The level of Tregs were measured by flow cytometry. Kidney tissues were examined with HE staining. TFG - β expression was detected by immunohistochemistry. The expression level of TNF - a IL - 6, FoxO1, NF - KB p65, COX - 2 were determined by western blotting and Real -time PCR. Results Saxagliptin decreased blood glucose, reduced food/water intakes and body weight, decreased serum lipid parameters （TC, TG, LDL）, ameliorated Cr, BUN, INF --y/IL - 10, Tregs levels. Saxagliptin significantly down - regulated the expressions of TFG - β, TNF - ct, IL - 6, FoxO1, NF - KB p65, COX - 2. Conclusion DPP - 4 inhibitor Saxagliptin could lessen kidney injury in type 2 diabetes mellitus rats by inhibiting inflammation and regulating immune function.
出处
《大连医科大学学报》
CAS
2017年第4期323-328,333,共7页
Journal of Dalian Medical University
基金
大连市医学卫生科学研究计划项目(大卫科发[2014]142号)
中华医学会医学教育分会中国高等教育学会医学教育专业委员会医学教育研究项目(2016B-YX013)
