Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.
Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.
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DOI：
10.1016/j.bbrc.2017.11.076
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发表时间：
2018
影响因子：
3.1
通讯作者：
Weiqin Yin;Shiqing Xu;Zai Wang;Hong-lin Liu;Liang Peng;Qing Fang;Tingting Deng;Wenjian Zhang;J. Lou
中科院分区：
文献类型：
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作者：
Weiqin Yin;Shiqing Xu;Zai Wang;Hong-lin Liu;Liang Peng;Qing Fang;Tingting Deng;Wenjian Zhang;J. Lou
基于GLP-1的治疗通过刺激胰岛素分泌和抑制胰高血糖素分泌来改善糖尿病。近年来，越来越多的研究表明GLP-1对糖尿病肾病也有一定的保护作用。这些研究大多集中在肾小球，但GLP-1对肾小管间质和肾小管的影响尚不清楚。本研究采用链脲佐菌素（STZ）诱导的糖尿病肾病大鼠模型，观察了重组人胰高血糖素样肽-1（rhGLP-1）对糖尿病肾病大鼠肾脏的保护作用，以及对炎症和肾小管间质损伤的影响。结果表明，rhGLP-1可降低尿白蛋白，而不影响体重和摄食量。rhGLP-1可轻度升高血清C肽水平，但对空腹血糖无明显降低作用。糖尿病肾病大鼠除肾小球硬化外，肾小管间质纤维化严重。rhGLP-1可减轻这些病变。rhGLP-1可降低肾小管组织和人近端肾小管细胞（HK-2细胞）中促纤维化因子I型胶原、α-SMA、纤连蛋白以及炎症因子MCP-1和TNFα的表达。rhGLP-1能显著抑制肾小管组织和HK-2细胞NF-κB、MAPK的磷酸化。GLP-1对HK-2细胞TNFα、MCP-1、I型胶原和α-SMA表达的抑制作用可通过阻断NF-κB或MAPK来模拟。提示rhGLP-1通过抑制MAPK和NF-κB的磷酸化而减轻肾小管间质损伤，发挥肾脏保护作用。因此，rhGLP-1有可能成为治疗糖尿病肾病的潜在药物。
GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, α-SMA, fibronectin, and inflammation factors MCP-1 and TNFα in tubular tissue and human proximal tubular cells (HK-2 cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-κB, MAPK in both diabetic tubular tissue and HK-2 cells. The inhibition of the expression of TNFα, MCP-1, collagen I and α-SMA in HK-2 cells by GLP-1 could be mimicked by blocking NF-κB or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injuryviainhibiting phosphorylation of MAPK and NF-κB. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy.