Application of PNR Detection in the Diagnosis and Drug-efficacy Evaluation of Diabetic Kidney Disease in Rats

doi:10.12300/j.issn.1674-5817.2024.044

Abstract

Abstract:

Objective This study aims to monitor the mRNA ratio of podocin to nephrin (PNR) in glomerular podocytes of early diabetic kidney disease (DKD) rat models. The feasibility of using PNR as an early diagnostic indicator for DKD was evaluated by comparing it with the urinary albumin-to-creatinine ratio (U-ACR). Additionally, the early intervention effects of valsartan and fosinopril sodium on DKD were compared. Methods The DKD rat model was established by caudal intravenous injection of streptozotocin (STZ) at a dosage of 60 mg/kg. The early changes in PNR and U-ACR were monitored and compared, followed by timely intervention with valsartan and fosinopril sodium. Hematoxylin and eosin staining (HE) was used to observe glomerular structure, while transmission electron microscopy examined the ultrastructure of glomerular podocytes. Results PNR reached the critical value(≥1) on day 9 after modeling, earlier than U-ACR, which reached the critical value(≥30 mg/g) on day 15. Intervention with valsartan and fosinopril sodium on day 9 after modeling significantly reduced U-ACR (P < 0.05), with low-dose valsartan showing better results than high-dose (P>0.05), while high-dose fosinopril sodium outperformed low-dose (P>0.05). Both low doses of valsartan and fosinopril sodium significantly reduced PNR (P<0.05), with no significant effect observed for high doses. The interventions with valsartan and fosinopril sodium improved and maintained glomerular structure and podocyte arrangement. Conclusion PNR changes earlier than U-ACR, indicating its potential as an early diagnostic marker for DKD in rats. Early intervention with valsartan and fosinopril sodium demonstrates a therapeutic effect on DKD in rats.

Key words: PNR, Urinary albumin-to-creatinine ratio (U-ACR), Diabetic kidney disease, Proteinuria prevention, Rats

CLC Number:

R587.1

ZHANG Naiqun,YUAN Piaopiao,CAO Linrong,et al. Application of PNR Detection in the Diagnosis and Drug-efficacy Evaluation of Diabetic Kidney Disease in Rats[J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 543-549. DOI: 10.12300/j.issn.1674-5817.2024.044.

Figures/Tables 3

References 16

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造模后时间 Time after molding/d	U-ACR/(mg·g^-1)		PNR
造模后时间 Time after molding/d	正常组 Normal	模型组 Model	正常组 Normal	模型组 Model
3	12.69±3.69	ND	0.85±0.40	0.39±0.19
5	13.29±4.05	ND	0.88±0.31	0.64±0.45
7	13.02±3.7	ND	0.86±0.37	0.66±0.10
9	12.14±3.27	9.45±6.23	0.91±0.27	1.26±0.11
11	11.96±3.21	18.19±8.75	0.90±0.25	1.70±0.65
13	13.88±4.02	ND	0.89±0.30	1.63±0.63
15	12.73±3.98	72.59±19.51	0.87±0.38	1.25±0.17
17	13.01±2.98	77.68±11.16	0.91±0.42	2.54±0.20

造模后时间 Time after molding/d	U-ACR/(mg·g^-1)		PNR
造模后时间 Time after molding/d	正常组 Normal	模型组 Model	正常组 Normal	模型组 Model
3	12.69±3.69	ND	0.85±0.40	0.39±0.19
5	13.29±4.05	ND	0.88±0.31	0.64±0.45
7	13.02±3.7	ND	0.86±0.37	0.66±0.10
9	12.14±3.27	9.45±6.23	0.91±0.27	1.26±0.11
11	11.96±3.21	18.19±8.75	0.90±0.25	1.70±0.65
13	13.88±4.02	ND	0.89±0.30	1.63±0.63
15	12.73±3.98	72.59±19.51	0.87±0.38	1.25±0.17
17	13.01±2.98	77.68±11.16	0.91±0.42	2.54±0.20

组别 Group	U-ACR/(mg·g^-1)		PNR
组别 Group	给药前 0 week	给药4周 4 weeks	给药前 0 week	给药4周 4 weeks
正常对照 Normal control (0.9%NS)	11.69±3.15	11.45±3.25	0.92±0.21	0.89±0.17
模型对照 Model control (0.9%NS)	17.96±6.45	896.12±62.89 ^**	1.24±0.11	1.64±0.08 ^**
缬沙坦低剂量 Valsartan 25 mg/kg	18.08±7.03	408.99±78.03 ^△△	1.16±0.14	0.53±0.13 ^△△
缬沙坦高剂量 Valsartan 50 mg/kg	18.86±6.90	480.97±94.34 ^△△	1.14±0.24	1.28±0.44
福辛普利钠低剂量 Fosinopril 30 mg/kg	18.73±6.82	314.93±67.81 ^△△	1.26±0.22	0.92±0.28 ^△△
福辛普利钠高剂量 Fosinopril 60 mg/kg	17.86±5.92	236.61±43.55 ^△△	1.17±0.21	2.14±0.29

组别 Group	U-ACR/(mg·g^-1)		PNR
组别 Group	给药前 0 week	给药4周 4 weeks	给药前 0 week	给药4周 4 weeks
正常对照 Normal control (0.9%NS)	11.69±3.15	11.45±3.25	0.92±0.21	0.89±0.17
模型对照 Model control (0.9%NS)	17.96±6.45	896.12±62.89 ^**	1.24±0.11	1.64±0.08 ^**
缬沙坦低剂量 Valsartan 25 mg/kg	18.08±7.03	408.99±78.03 ^△△	1.16±0.14	0.53±0.13 ^△△
缬沙坦高剂量 Valsartan 50 mg/kg	18.86±6.90	480.97±94.34 ^△△	1.14±0.24	1.28±0.44
福辛普利钠低剂量 Fosinopril 30 mg/kg	18.73±6.82	314.93±67.81 ^△△	1.26±0.22	0.92±0.28 ^△△
福辛普利钠高剂量 Fosinopril 60 mg/kg	17.86±5.92	236.61±43.55 ^△△	1.17±0.21	2.14±0.29

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