Division of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Ren Fail. 2024 Dec;46(2):2394637. doi: 10.1080/0886022X.2024.2394637. Epub 2024 Aug 27.
Recent studies have reported that helix B surface polypeptide (HBSP), an erythropoietin derivative, exhibits strong tissue protective effects, independent of erythropoietic effects, in a renal ischemia-reperfusion (IR) injury model. Meanwhile, the transforming growth factor-β (TGF-β) superfamily member glial cell line-derived neurotrophic factor (GDNF) demonstrated protective effect on podocytes . Using a rat puromycin aminonucleoside nephropathy (PAN) model, this study observed the renal protective effect of HBSP and investigated its renal protective effect on podocytes and mechanism related to GDNF.
Rats nephropathy model was induced by injection of 60 mg/kg of PAN the tail vein. Rats in the PAN + HBSP group were injected intraperitoneally with HBSP (8 nmol/kg) 4 h before the model was induced, followed by intraperitoneal injections of HBSP once every 24 h for 7 consecutive days. The 24-hour urinary protein level was measured once every other day, and blood and renal tissue samples were collected on the 7th day for the examination of renal function, complete blood count, renal pathological changes and the expression levels of GDNF.
Compared with the control group, the PAN nephropathy rat model showed a large amount of urinary protein. The pathological manifestations were mainly extensive fusion and disappearance of foot processes, along with vacuolar degeneration of podocytes and their separation from the glomerular basement membrane. GDNF expression was upregulated. Compared with the PAN + vehicle group, the PAN + HBSP group showed decreased urinary protein ( < 0.05). Pathological examination revealed ameliorated glomerular injury and vacuolar degeneration of podocytes. The expression of GDNF in the PAN nephropathy group was increased, when compared with the control group. The greatest expression of GDNF observed in the PAN + HBSP group ( < 0.05).
The expression of GDNF in the kidney of PAN rat model was increased. HBSP reduced urinary protein, ameliorated pathological changes in renal podocytes, increased the expression of GDNF in the PAN rat model. HBSP is likely to exert its protective effects on podocytes through upregulation of GDNF expression.
最近的研究报告称，红细胞生成素衍生物螺旋 B 表面多肽（HBSP）在肾缺血再灌注（IR）损伤模型中具有很强的组织保护作用，且不依赖于红细胞生成作用。同时，神经胶质细胞衍生神经营养因子（GDNF）是转化生长因子-β（TGF-β）超家族成员，对足细胞具有保护作用。本研究采用大鼠嘌呤霉素氨基核苷肾病（PAN）模型，观察 HBSP 的肾保护作用，并探讨其对足细胞的保护作用及其与 GDNF 相关的机制。
通过尾静脉注射 60mg/kg 的嘌呤霉素氨基核苷诱导大鼠肾病模型。在诱导模型前 4 小时，PAN+HBSP 组大鼠腹腔内注射 HBSP（8nmol/kg），随后每 24 小时腹腔内注射一次，连续 7 天。每隔一天测量一次 24 小时尿蛋白水平，第 7 天采集血和肾组织样本，检查肾功能、全血细胞计数、肾组织病理学变化和 GDNF 表达水平。
与对照组相比，PAN 肾病大鼠模型的尿蛋白大量增加。病理表现主要为广泛融合和足突消失，同时伴有足细胞空泡变性和与肾小球基底膜分离。GDNF 表达上调。与 PAN+载体组相比，PAN+HBSP 组尿蛋白减少（<0.05）。病理检查显示肾小球损伤和足突细胞空泡变性得到改善。与对照组相比，PAN 肾病组 GDNF 的表达增加。在 PAN+HBSP 组观察到 GDNF 的表达最高（<0.05）。
PAN 大鼠模型肾组织中 GDNF 的表达增加。HBSP 减少尿蛋白，改善肾足突细胞的病理变化，增加 PAN 大鼠模型中 GDNF 的表达。HBSP 可能通过上调 GDNF 的表达发挥对足细胞的保护作用。
