Zhang Feifei, Liu Junchao, Yu Jian, Sun Wen, Wang Yonghong, Fan Teng, Sun Yanyan, Han Xinghui
Children's Hosptial of Fudan University Department of Traditional Chinese Medicine, Shanghai 201102, China.
Evid Based Complement Alternat Med. 2022 Jan 31;2022:9921679. doi: 10.1155/2022/9921679. eCollection 2022.
This study aimed to investigate the effects of Nephropathy Prescription I on the expression of angptl3, nephrin, and podocin, in addition to its protective effects on podocytes in mice with adriamycin-induced nephropathy.
BALB/c mice were randomly divided into the control (C), adriamycin (Model or M), adriamycin + Nephropathy Prescription I ( + ), adriamycin + prednisone acetate ( + ), and adriamycin + Nephropathy Prescription I + prednisone acetate groups ( + + ). All mice except those in the C group in the experimental groups were treated with a single tail vein injection of adriamycin. The urine albumin-creatinine ratio was measured before model establishment and on the 7th day, 14th day, 21st day, and 28th day of doxorubicin injection. All the mice were sacrificed on the 29th day. Blood samples were collected to observe biochemical indicators in the serum. The morphological structure and podocyte ultrastructure in the kidney were observed using light and electron microscopy, respectively. The expression of angptl3, nephrin, and podocin at the mRNA and protein levels was detected by real-time PCR and western blotting, respectively.
Following modeling with adriamycin, albuminuria was observed in urine samples in the first week, and the urinary protein/creatinine ratio increased maximally in the fourth week in the group ( < 0.05). In contrast, the urinary protein/creatinine ratio significantly decreased ( < 0.05) in the third week in the ( + ) group compared to that in the group. Similarly, this ratio decreased in the ( + ) and ( + + ) groups compared to that in the group throughout the experiment. Compared with the C group, serum albumin content and the expression of nephrin and podocin decreased ( < 0.05), whereas blood lipid level and the expression of angptl3 increased ( < 0.05) in the group. Glomerular foot process fusion was observed in this group using electron microscopy. In all the intervention groups, serum albumin content and the expression of nephrin and podocin increased ( < 0.05), whereas blood lipid level and the expression of angptl3 decreased ( < 0.05), with alleviated glomerular foot process injury observed particularly in the ( + + ) group.
The Nephropathy Prescription I can alleviate albuminuria, increase serum albumin levels, lower blood lipid levels, and reduce the fusion of foot processes of podocytes in mice with adriamycin-induced nephropathy. The protective effects of the Nephropathy Prescription I may function by reducing Angptl3 expression and increasing nephrin and podocin expression.
本研究旨在探讨肾病方剂I对血管生成素样蛋白3(angptl3)、nephrin和足突蛋白(podocin)表达的影响,以及其对阿霉素诱导的肾病小鼠足细胞的保护作用。
将BALB/c小鼠随机分为对照组(C)、阿霉素组(模型组或M组)、阿霉素+肾病方剂I组(+组)、阿霉素+醋酸泼尼松组(+组)和阿霉素+肾病方剂I+醋酸泼尼松组(++组)。除C组外,实验组所有小鼠均经尾静脉单次注射阿霉素。在造模前及注射阿霉素后的第7天、14天、21天和28天测量尿白蛋白-肌酐比值。所有小鼠在第29天处死。采集血样观察血清中的生化指标。分别用光学显微镜和电子显微镜观察肾脏的形态结构和足细胞超微结构。分别通过实时荧光定量PCR和蛋白质免疫印迹法检测angptl3、nephrin和podocin在mRNA和蛋白质水平的表达。
阿霉素造模后,第1周尿样中出现蛋白尿,模型组第4周尿蛋白/肌酐比值最高(P<0.05)。相比之下,+组在第3周时尿蛋白/肌酐比值与模型组相比显著降低(P<0.05)。同样,在整个实验过程中,+组和++组的该比值与模型组相比均降低。与C组相比,模型组血清白蛋白含量以及nephrin和podocin的表达降低(P<0.05),而血脂水平和angptl3的表达升高(P<0.05)。该组经电子显微镜观察可见肾小球足突融合。在所有干预组中,血清白蛋白含量以及nephrin和podocin的表达均升高(P<0.05),而血脂水平和angptl3的表达降低(P<0.05),尤其在++组观察到肾小球足突损伤减轻。
肾病方剂I可减轻阿霉素诱导的肾病小鼠的蛋白尿,提高血清白蛋白水平,降低血脂水平,并减少足细胞足突融合。肾病方剂I的保护作用可能通过降低Angptl3表达以及增加nephrin和podocin表达来发挥。