›› 2012, Vol. 32 ›› Issue (10): 1283-.doi: 10.3969/j.issn.1674-8115.2012.10.001

• Original article (Basic research) •     Next Articles

Metabotropic glutamate receptor 1/5 agonist improves doxorubicin-induced renal injury in mice

TAO Hua, GU Le-yi, WANG Li-hua, YAN Yu-cheng, NI Zhao-hui, QIAN Jia-qi   

  1. Renal Division, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
  • Online:2012-10-28 Published:2012-11-05
  • Supported by:

    National Nature Science Foundation of China, 30971363 ; Nature Science Foundation of Shanghai, 08ZR1413200; Shanghai Science and Technology Committee Foundation, 07JC14037, 10JC1410200


Objective To investigate the effects of selective agonist for metabotropic glutamate receptors 1 and 5 (mGluR1/5), (S)-3,5-dihydroxyphenylglycine (DHPG), on the doxorubicin (ADR)-induced nephrosis in mice. Methods Eighteen 6-week-old male BALB/c mice were randomly divided into control group, ADR group (nephrosis model established by intravenous injection of ADR) and ADR+DHPG group (pretreatment with DHPG injection before model establishment), with 6 mice in each group. Twenty-four-hour urinary albumine levels were measured by enzyme-linked immunosorbent assay (ELISA), and the foot processes effacement and the width of foot processes were determined with electron microscopy. Laser confocal microscope with immunofluorescence staining was employed to detect the expression of nephrin and desmin, and the expression of WT-1 in glomerulus was determined by immunohistochemistry. Besides, the apoptosis of podocytes was detected by TUNEL staining. Results Twenty-four-hour urinary albumine levels were (1.67±0.22) mg, (22.55±2.34) mg and (8.23±2.74) mg in control group, ADR group, and ADR+DHPG group respectively, and there were significant differences among groups (P<0.01). Compared with ADR group, the width of foot processes in ADR+DHPG was shorter, the expression of desmin was lower, and the expression of nephrin was higher. The number of WT-1 positive cells was negatively related to the number of apoptotic cells in glomerulus (R2=0.8 482,P<0.05), and the number of apoptotic podocytes in ADR+DHPG group was significantly smaller than that in ADR group (P<0.01). Conclusion Selective mGluR 1/5 agonist DHPG may inhibit ADRinduced foot processes fusion of podocytes and decreased expression of nephrin, reduce cell apoptosis, and attenuate urinary albumine in ADR-induced nephrosis in mice.

Key words: metabotropic glutamate receptor 1/5, albuminuria, podocyte