Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (6): 1337-1346.doi: 10.13481/j.1671-587X.20210601

• Research in basic medicine •     Next Articles

Protective effect of 12/15-lipoxygenase gene knockout on kidney tissue of obesity-related glomerulopathy model mice and its mechanism

Mimi REN,Menghan GAO,Jing WANG,Jiamei LAI,Jinyu YU,Hang YUAN()   

  1. Department of Nephrology,First Hospital,Jilin University,Changchun 130021,China
  • Received:2021-06-29 Online:2021-11-28 Published:2021-12-14
  • Contact: Hang YUAN E-mail:hangyuan75@foxmail.com

Abstract: Objective

To explore the protective effect of 12/15-lipoxygenase (12/15-LO) gene knockout(12/15-LOKO) on the kidney tissue of the obese mice induced by high-fat diet (HFD), and to clarify its role in the progression of kidney disease.

Methods

A total of 16 12/15-LOKO mice and 16 WT mice were randomly divided into HFD group and standard diet (SFD) group,respectively,and there were 8 mice in each group. The mice in HFD group were fed with HFD,and the mice in SFD were fed with SFD, namely WT+HFD group, WT+SFD group, LOKO+HFD group, and LOKO+SFD group.The 24 h urine of mice in various groups was collected after feeding for 1, 8, and 14 weeks. The body weights, double kidney weights and tibia lengths of hind legs of mice in various groups were detected.The 24 h urine of the mice in various groups was collected after 1,8, and 14 week,the urinary protein level,urinary perotein creatinine ratios(PCR), and urinary microalbumin creartinine ratio(ACR) of the mice were detected.The blood glucose levels of the mice in various groups were detected by glucose tolerance test (GTT),and the mRNA levels of adiponectin, tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1),and transforming growth factor-β1(TGF-β1) in kindey cortex tissue of the mice in various groups were detected by Real-time fluorescence quantitative PCR (RT-qPCR)method.ELISA method was used to detect the levels of adiponectin,TNF-α,IL-6,angioteinsinⅡ(AngⅡ)and insulin in serum of the mice in various groups.PAS staining was used to observe the pathomorphology of kidney tissue and glomerularareas of the mice in various groups,and Western blotting method was used to detect the expressions of TGF-β1 and PAI-1β proteins in kidney tissue of the mice in various groups.

Results

The body weight, kidney weight and glomerular area of the mice in HFD group were significantly higher than those in SFD group (P<0.01),and the ACR and PCR of the mice in WT+HFD group were higher than those in SFD group (P<0.05); compared with LOKO+HFD group, the fasting blood glucose level of the mice in WT+HFD group was increased (P<0.05). The expression levels of TNF- α,IL-6,and MCP-1 mRNA in kidney cortex tissue of the mice in WT+HFD group were significantly higher than those in WT+SFD group (P<0.05). Compared with LOKO+HFD group,the expression levels of IL-6 and MCP-1 mRNA in kidney cortex tissue of the mice in WT+HFD group were increased(P<0.05), while the expression level of adiponectin mRNA was decreased significantly (P<0.05). The expression levels of PAI-1 and TGF-β1 mRNA in kidney cortex tissue of the mice in WT+HFD group were higher than those of the mice in WT+SFD group(P<0.05).The expression levels of PAI-1 and TGF-β1 mRNA in kidney cortex tissue of the mice in LOKO+HFD group were lower than those of the mice in WT+HFD group(P<0.01).

Conclusion

12/15-LOKO can improve insulin resistance, proteinuria level and degree of glomerular hypertrophy of the obese mice, and its mechanism may be related to the inhibition the expressions of inflammatory factors such as TNF- α and IL-6 in kidney tissue and affecting the expressions of PAI-1 and TGF-β1 mRNA,so as to play a protective role in kidney.

Key words: 12/15-lipoxygenase, obesity, glomerular disease, inflammation

CLC Number: 

  • R692.6