Department of Endocrinology, People's Hospital of Shenzhen Baoan District, The Second School of Clinical Medicine, Southern Medical University, The Second Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
Department of No. 1 Cadres, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
J Diabetes Res. 2021 Apr 5;2021:8873956. doi: 10.1155/2021/8873956. eCollection 2021.
To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats.
DN rats were randomly divided into two groups ( = 10) and were injected with liraglutide or normal saline twice a day. The 24-hour urine microalbumin content and biochemical index levels were measured. qRT-PCR was performed to detect the expression of miR-34a in the kidney and liver tissues. The levels of SIRT1, HIF-1a, Egr-1, and TGF-1 in kidney and liver tissues were determined using qRT-PCR, western blot, and immunohistochemistry. Electron microscopy and HE staining were used to observe the ultrastructure and pathological changes.
Liraglutide treatment in DN rats decreased blood glucose, 24-hour urine microalbumin, TC, TG, LDL-C, UA, Cr, UREA, ALT, and AST levels and increased the level of HDL-C ( < 0.05). Compared with the control group, the miR-34a levels were significantly decreased in kidney and liver tissues followed by liraglutide treatment ( < 0.05). The levels of SIRT1 in the liraglutide group are significantly higher than those in the control group with the kidney and liver tissues ( < 0.05). Conversely, the contents of HIF-1a, Egr-1, and TGF-1 were significantly lower in the liraglutide group than in the control group ( < 0.05). Electron microscopy showed that the kidney of the liraglutide-treated group exhibited minor broadening of the mesangial areas, fewer deposits, and a well-organized foot process. HE staining revealed that the kidney of the liraglutide-treated rats had a more regular morphology of the glomerulus and Bowman sac cavity and lighter tubular edema. Additionally, the liraglutide-treated DN rats had a clear hepatic structure, a lower degree of steatosis, and mild inflammatory cell infiltration.
Liraglutide, through its effect on the miR-34a/SIRT1 pathway, may have a protective role in the kidney and liver of DN rats.
通过 miR-34a/SIRT1 通路及相关因子探讨利拉鲁肽对糖尿病肾病（DN）大鼠肾脏和肝脏的调控作用。
将 DN 大鼠随机分为两组（每组 n=10），每天两次分别注射利拉鲁肽或生理盐水。测量 24 小时尿微量白蛋白含量和生化指标水平。采用 qRT-PCR 检测肾脏和肝脏组织中 miR-34a 的表达。采用 qRT-PCR、western blot 和免疫组化法测定肾脏和肝脏组织中 SIRT1、HIF-1a、Egr-1 和 TGF-β1 的水平。电镜和 HE 染色观察超微结构和病理变化。
利拉鲁肽治疗可降低 DN 大鼠的血糖、24 小时尿微量白蛋白、TC、TG、LDL-C、UA、Cr、UREA、ALT 和 AST 水平，升高 HDL-C 水平（<0.05）。与对照组相比，利拉鲁肽治疗后肾脏和肝脏组织中的 miR-34a 水平显著降低（<0.05）。利拉鲁肽组的 SIRT1 水平在肾脏和肝脏组织中明显高于对照组（<0.05）。相反，利拉鲁肽组的 HIF-1a、Egr-1 和 TGF-β1 含量明显低于对照组（<0.05）。电镜显示，利拉鲁肽治疗组的肾小球系膜区稍有增宽，沉积物减少，足突排列整齐。HE 染色显示，利拉鲁肽治疗大鼠的肾小球形态更规则，鲍曼囊腔更清晰，肾小管水肿较轻。此外，利拉鲁肽治疗的 DN 大鼠肝脏结构清晰，脂肪变性程度较低，炎症细胞浸润较轻。
利拉鲁肽可能通过 miR-34a/SIRT1 通路对 DN 大鼠的肾脏和肝脏发挥保护作用。
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