Expression of autophagy and ASPPs in early acute kidney injury of aged rats

doi:10.3877/cma.j.issn.2095-3216.2019.05.005

Abstract

Abstract:

Objective

To observe the expression changes of autophagy-related proteins and apoptosis-stimulating proteins of p53 (ASPPs) in early renal injury, and to explore whether autophagy-related proteins and ASPPs may become early biomarkers of acute kidney injury (AKI) in aged rats.

Methods

A cisplatin-induced AKI model was established in both young and old rats. Male SD rats were randomly divided into sham operation group and cisplatin model group, and a matched number of male young SD rats were as controls. Rats in the model group were given intraperitoneal injection of cisplatin 4 ml/kg, while rats in the sham group injected with normal saline 4 mg/kg. Rats were examined for Scr and BUN at 12 h, 1 day, 3 days, 5 days, and 7 days, and the pathological changes of rat kidney were observed by light microscopy. Ultrastructural changes and autophagosomes in rat renal tubular epithelial cells were observed under transmission electron microscopy. Western blotting was used to detect the expression of Beclin 1, LAMP-2, p62, p53, iASPP and ASPP1 in kidney tissues.

Results

After 12 hours of cisplatin induction, compared with the sham group, there was no significant change in Scr of young and old rats (P>0.05), and electron microscopy showed that autophagosomes in rat renal tubular epithelial cells appeared and the number increased significantly. The expression levels of Beclin 1, p62, LAMP-2, and p53 in the kidney of aged rats were significantly increased (P<0.05), with the expression level of iASPP being significantly decreased (P<0.05). And the renal expression of Beclin 1, LAMP-2, and p53 changed earlier in the old rats than in the young rats (P<0.05).

Conclusions

Autophagy and ASPPs appeared in the early stage of rat AKI, and reactive autophagy had started before Scr began to rise. Autophagy-associated proteins and ASPPs are expected to be earlier markers of AKI, and may be new targets for early intervention of AKI, which still need further research.

Key words: Cisplatin, Acute kidney injury, Biomarker, ASPPs, Autophagy

Qinglin Li, Xiaodan Wang, Bo Fu, Feihu Zhou. Expression of autophagy and ASPPs in early acute kidney injury of aged rats[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2019, 08(05): 213-218.

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Figures/Tables 5

References 27

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项目	Sham	12 h	1 d	3 d	5 d	7 d
青年鼠-Scr	19.6±1.7	20.2±1.6	20±1.6	136.2±21.9^b	70.6±6.7^b	29.6±2.1^b
老年鼠- Scr	25.0±1.1	26.4±1.1	44.6±2.9^b	415.8±65.5^b	840.6±67.1^b	1 298.4±196.1^b
青年鼠-BUN	4.2±0.3	4.5±0.3	5.6±0.6^a	14.0±3.2^b	15.0±2.6^b	5.5±0.7^a
老年鼠-BUN	4.2±0.5	5.9±0.4^b	7.9±1.0^b	34.7±3.6^b	67.5±6.7^b	90.3±17.6^b

项目	Sham	12 h	1 d	3 d	5 d	7 d
青年鼠-Scr	19.6±1.7	20.2±1.6	20±1.6	136.2±21.9^b	70.6±6.7^b	29.6±2.1^b
老年鼠- Scr	25.0±1.1	26.4±1.1	44.6±2.9^b	415.8±65.5^b	840.6±67.1^b	1 298.4±196.1^b
青年鼠-BUN	4.2±0.3	4.5±0.3	5.6±0.6^a	14.0±3.2^b	15.0±2.6^b	5.5±0.7^a
老年鼠-BUN	4.2±0.5	5.9±0.4^b	7.9±1.0^b	34.7±3.6^b	67.5±6.7^b	90.3±17.6^b

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