Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Department of Pediatric, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Diabetes Res Clin Pract. 2019 Oct;156:107755. doi: 10.1016/j.diabres.2019.05.034. Epub 2019 May 28.
The role of chronic inflammation initiated by persistent hyperglycemia in podocyte injury has attracted increasing attention. The advanced glycation end products (RAGE) receptor- nuclear factor-kappa B (NF-кB) signaling pathway is involved in the occurrence of inflammation. We speculate that treatment with human umbilical cord mesenchymal stem cells (hUCMSCs) combined with resveratrol can block this signaling pathway and protect podocyte function.
Non obesity diabetes(NOD) mice were randomly divided into 5 groups: NOD-T1DM, Res, hUCMSCs, hUCMSCs + Res and insulin (INS)groups. Mice without diabetes were classified as NOD control group(NOD group). Blood glucose(BG), blood urea nitrogen(BUN), serum creatinine(SCr), 24-h urine albumin excretion rate (UAER) were measured. The expression of nephrin, WT1 and RAGE, MCP-1 in renal tissues were detected by Western blot, expression of NF-кB protein(P65) was determined by immunohistochemistry.
The combined treatment of hUCMSCs and Resveratrol can reduce BG, BUN, SCr, 24-h UAER, and the expression of the inflammatory factors MCP-1, RAGE and NF-кB; increase the number of podocytes and the expression of the podocyte-related proteins nephrin and WT1 in type 1 diabetes mellitus, and improve renal pathological structure.
Combining of hUCMSCs and resveratrol can better protect renal podocyte function, and the effects on the reduction of blood glucose and renal injury are better than those obtained by insulin treatment. This indicated that the combination of Res and hUCMSCs may be a novel therapeutic method for the treatment of DN.
持续性高血糖引起的慢性炎症在肾小球脏层上皮细胞（足细胞）损伤中的作用引起了越来越多的关注。晚期糖基化终产物（RAGE）受体-核因子-κB（NF-κB）信号通路参与了炎症的发生。我们推测，人脐带间充质干细胞（hUCMSCs）联合白藜芦醇治疗可以阻断这一信号通路，保护足细胞功能。
将非肥胖糖尿病（NOD）小鼠随机分为 5 组：NOD-T1DM 组、白藜芦醇组、hUCMSCs 组、hUCMSCs+白藜芦醇组和胰岛素（INS）组。无糖尿病的小鼠分为 NOD 对照组（NOD 组）。检测血糖（BG）、血尿素氮（BUN）、血清肌酐（SCr）、24 小时尿白蛋白排泄率（UAER）。Western blot 检测肾组织中nephrin、WT1 和 RAGE 的表达，免疫组化法检测 NF-κB 蛋白（P65）的表达。
hUCMSCs 联合白藜芦醇治疗可降低 1 型糖尿病小鼠的 BG、BUN、SCr、24 小时 UAER，以及炎症因子 MCP-1、RAGE 和 NF-κB 的表达；增加足细胞数量及足细胞相关蛋白 nephrin 和 WT1 的表达，改善肾脏病理结构。
hUCMSCs 联合白藜芦醇能更好地保护肾脏足细胞功能，对降低血糖和肾脏损伤的作用优于胰岛素治疗。这表明 Res 和 hUCMSCs 的联合应用可能是治疗糖尿病肾病的一种新的治疗方法。
