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    王娥, 赵唐明, 郑辉, 季嘉玲, 甘卫华, 张爱青. tRF-003634对阿霉素肾病小鼠足细胞凋亡的作用和机制研究[J]. 徐州医科大学学报, 2022, 42(12): 866-873. DOI: 10.3969/j.issn.2096-3882.2022.12.002
    引用本文: 王娥, 赵唐明, 郑辉, 季嘉玲, 甘卫华, 张爱青. tRF-003634对阿霉素肾病小鼠足细胞凋亡的作用和机制研究[J]. 徐州医科大学学报, 2022, 42(12): 866-873. DOI: 10.3969/j.issn.2096-3882.2022.12.002
    shu
    The effect and mechanism of tRF-003634 on podocyte apoptosis in mice with adriamycin nephropathy[J]. Journal of Xuzhou Medical University, 2022, 42(12): 866-873. DOI: 10.3969/j.issn.2096-3882.2022.12.002
    Citation: The effect and mechanism of tRF-003634 on podocyte apoptosis in mice with adriamycin nephropathy[J]. Journal of Xuzhou Medical University, 2022, 42(12): 866-873. DOI: 10.3969/j.issn.2096-3882.2022.12.002
    shu

    tRF-003634对阿霉素肾病小鼠足细胞凋亡的作用和机制研究

    The effect and mechanism of tRF-003634 on podocyte apoptosis in mice with adriamycin nephropathy

      摘要
    • 摘要: 目的：探究tRF-003634(tRNA-derived fragment 003634)对阿霉素(Adriamycin)肾病小鼠足细胞凋亡的作用及机制。方法：(1)用BALB/c小鼠作为对象来建立阿霉素(10mg/kg)肾病模型。取20只BALB/c小鼠随机分为：对照组、阿霉素组(ADR组)、ADR+tRF-003634 agomir组、ADR+tRF-003634 NC组(n=5)。检测各组小鼠的血清生化指标水平，HE、PAS染色评估小鼠肾脏病理变化；Real-Time PCR法检测各组肾脏中tRF-003634的表达水平；Western blot法用来检验肾脏组织中caspase3、cleaved caspase3和p53的蛋白表达水平。(2)体外用阿霉素(1 μg/mL)诱导足细胞凋亡。依据不同干预因素将足细胞分为：对照组、ADR组、ADR+tRF-003634 mimics组和ADR+tRF-003634 NC组。Real-Time PCR法测定各组tRF-003634的表达水平；Western blot法用来测定不同组别间足细胞中caspase3、cleaved caspase3和p53的相对表达。(3)将足细胞分成：对照组、ADR组、ADR+SB203580组和SB203580组。利用Western blot法来检测每组p-p38MAPK和p-Hsp27的蛋白相对表达，Real-time PCR法检测tRF-003634的表达水平。结果：(1)与对照组相比，ADR组的病理变化显著加重，tRF-003634的表达水平下降，cleaved caspase3和p53的表达水平显著上升（P<0.05）。与ADR组相比，ADR+tRF-003634 agomir组小鼠24h尿蛋白和血清尿素氮水平显著下降(P<0.05)，病理改变减轻；tRF-003634表达水平明显上升，cleaved caspase3和p53表达水平显著下降(P<0.05)。(2)与对照组相比，ADR组足细胞中tRF-003634表达水平显著下降，cleaved caspase3和p53表达水平显著上升(P<0.05)。与ADR组相比，ADR+tRF-003634 mimics组的tRF-003634表达水平显著上升(P<0.05)，cleaved caspase3和p53表达水平显著下降(P<0.05)。(3)与对照组相比，ADR组p-p38MAPK和p-Hsp27表达上调，tRF-003634表达下降(P<0.05)；与ADR组相比，ADR+SB203580组p-p38MAPK和p-Hsp2蛋白表达显著下降，tRF-003634表达上升(P<0.05)。结论：tRF-003634能够抑制足细胞凋亡，减轻阿霉素诱导的肾脏病理损伤。tRF-003634可能作为MAPK通路的下游效应分子改善足细胞凋亡，为慢性肾脏病的诊治提供新的思路。

       

      Abstract: ob＜x＞jective：To explore the effect and mechanism of tRF-003634(tRNA-derived fragment 003634) on podocyte apoptosis in mice with adriamycin nephropathy . Methods：(1) BALB/c mice were used to establish a model of Adriamycin(10 mg/kg) nephropathy. 20 BALB/c mice were divided randomly into: control group, ADR group, ADR+tRF-003634 agomir group and ADR+tRF-003634 NC group(n=5). The serum biochemical indexes of mice in each group were detected, and the pathological changes of mice kidney were evaluated by HE and PAS staining ; The ex＜x＞pression level of TRF-003634 in each group was detected by Real-Time PCR; The protein ex＜x＞pressions of Caspase3, cleaved Caspase3 and p53 were detected by Western blot method. (2) Adriamycin (1 μg/mL) was used to induce podocyte apoptosis in vitro. Podocytes were divided into: control group, ADR group, ADR+tRF-003634 mimics group and ADR+tRF-003634 NC group according to different intervention factors. The Real-Time PCR method was used to detect the ex＜x＞pression level of tRF-003634 in each group; The relative ex＜x＞pression levels of caspase3, cleaved caspase3 and p53 in podocytes of each group were detected by Western blot method. (3) Podocytes were divided into: control group, ADR group, ADR+SB203580 group and SB203580 group. Western blot was used to detect the protein ex＜x＞pressions of p-p38MAPK and p-Hsp27 in each group, and Real-time PCR was used to detect the ex＜x＞pression of tRF-003634. Results：(1) Compared with the control group, the pathological changes of the ADR group increased significantly, the ex＜x＞pression level of tRF-003634 decreased, and the ex＜x＞pression levels of cleaved caspase3 and p53 increased significantly(P<0.05). Compared with the ADR group, the ADR+tRF-003634 agomir group mice 24h urine protein and serum urea nitrogen decreased significantly(P<0.05), and pathological changes were alleviated; The ex＜x＞pression level of tRF-003634 increased obviously, and cleaved caspase3 and p53 ex＜x＞pression levels were decreased obviously(P<0.05). (2) Compared with the control group, tRF-003634 decreased significantly in ADR podocytes, and the levels of cleaved caspase3 and p53 increased significantly(P<0.05). Compared with the ADR group, the ex＜x＞pression level of tRF-003634 in the tRF-003634 mimics group increased significantly (P<0.05), and the ex＜x＞pression levels of cleaved caspase3 and p53 decreased significantly (P<0.05). (3) Compared with the control group, the ex＜x＞pressions of p-p38MAPK and p-Hsp27 in the ADR group were up-regulated, and the ex＜x＞pression of tRF-003634 was down-regulated(P<0.05). Compared with the ADR group, the protein ex＜x＞pressions of p-p38MAPK and p-Hsp27 in the ADR+SB203580 group decreased significantly, and the ex＜x＞pression of tRF-003634 increased(P<0.05). Conclusion：tRF-003634 can inhibit the apoptosis of podocytes and alleviate the renal pathological damage induced by adriamycin. tRF-003634 may act as a downstream effector molecule of MAPK pathway to improve podocyte apoptosis and provide new ideas for the diagnosis and treatment of chronic kidney disease

       

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