Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China,
Department of Nephrology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China,
Kidney Blood Press Res. 2023;48(1):209-219. doi: 10.1159/000529444. Epub 2023 Feb 13.
Acute kidney injury (AKI) is a clinical emergency caused by the rapid decline of renal function caused by various etiologies. Growth differentiation factor 11 (GDF11) can promote renal tubular regeneration and improve kidney function in AKI, but the specific mechanism remains unclear. Herein, we investigated the effect and mechanisms of GDF11 in ameliorating AKI induced by ischemia-reperfusion (I/R).
An animal model of AKI was established by I/R method, and the changes of serum urea nitrogen and creatinine were measured to evaluate the AKI. Enzyme-linked immunosorbent assay (ELISA) was used to measure cytokines, malondialdehyde, superoxide dismutase, nitric oxide synthase, and arginase 1 levels. Flow cytometry was used to count the M1/M2 macrophages. IHC, WB, and q-PCR experiments were used to evaluate the expression of GDF11.
The changes in serum levels of urea nitrogen and creatinine after I/R suggest that an animal model of AKI induced by I/R was successfully established. AKI caused by I/R significantly changed the M1/M2 macrophage polarization balance, with an increase in M2 being significantly higher than M1 as well as increased oxidative stress. Treatment with GDF11 after I/R significantly increased the differentiation of M2 cells and inhibited the differentiation of M1 macrophages, as well as decreased oxidative stress.
GDF11 can promote the repair of AKI caused by I/R by regulating the balance of M1/M2 polarization in macrophages and oxidative stress.
急性肾损伤（AKI）是由各种病因引起的肾功能迅速下降导致的临床急症。生长分化因子 11（GDF11）可促进 AKI 中的肾小管再生并改善肾功能，但具体机制尚不清楚。在此，我们研究了 GDF11 改善缺血再灌注（I/R）引起的 AKI 的作用和机制。
采用 I/R 方法建立 AKI 动物模型，检测血清尿素氮和肌酐的变化来评估 AKI。酶联免疫吸附试验（ELISA）用于测量细胞因子、丙二醛、超氧化物歧化酶、一氧化氮合酶和精氨酸酶 1 的水平。流式细胞术用于计数 M1/M2 巨噬细胞。免疫组化、WB 和 q-PCR 实验用于评估 GDF11 的表达。
I/R 后血清尿素氮和肌酐水平的变化表明，成功建立了 I/R 诱导的 AKI 动物模型。I/R 引起的 AKI 明显改变了 M1/M2 巨噬细胞极化平衡，M2 的增加明显高于 M1，同时伴有氧化应激增加。I/R 后给予 GDF11 治疗可显著增加 M2 细胞的分化并抑制 M1 巨噬细胞的分化，同时降低氧化应激。
GDF11 可通过调节巨噬细胞 M1/M2 极化平衡和氧化应激来促进 I/R 引起的 AKI 的修复。
