Effect Of PPAR Gamma Agonist On The ANGPTL4 Level Of Serum And Renal Tissue And On Proteinuria In Purinamycin-Induced Nephrotic Rats

Background:Proteinuria is one of the main clinical manifestations of primary nephrotic syndrome,persistent proteinuria will affect the progress of kidney disease,leading to glomerular sclerosis and tubulointerstitial damage,thus effectively reduce proteinuria,can protect the kidney,kidney in animal model research found that PPAR gamma agonist can effectively to reduce the proteinuria in nephropathy rats,to protect the kidney function,but the mechanism is not clear,the small study found that elevated circulating ANGPTL4 can reduce urinary protein,and ANGPTL4 as PPAR gamma agonist regulating target,PPAR gamma agonist can regulate the generation of ANGPTL4 in peripheral tissues,so we speculated that PPAR gamma agonist may increase the expression of ANGPTL4 in peripheral tissues,so as to reduce the urinary protein,this paper aims to investigate the effect of PPAR gamma agonist on the excretion of proteinuria and the ANGPTL4 level in serum and renal tissue of purinamycin-induced nephrotic rats as well as its mechanism.Methods: Sixty male SD rats,purinamycin-induced nephrotic rat models of minimal change disease were established by intraperitoneal injection of puromycin aminonucleoside(PAN)(150mg/Kg),the health control group received equal volume of normal saline by intraperitoneal injection.Then rats were randomly divided into saline control group(intragastric treatment with normal saline,n=15),PAN control group(intragastric treatment with normal saline after injection of PAN,n=15),Pio0 group(intragastric treatment with pioglitazone was the same day as PAN injection,n=15),Pio4 group(intragastric treatment with pioglitazone 4 days after PAN injection,n=10)and Pio10 group(intragastric treatment with pioglitazone 10 days after PAN injection,n=5).the dose of pioglitazone was given with 10 mg/(kg.day).24 h urine volume,blood and renal tissue specimen were collected 4d,10 d and 21 d after model building.Biochemical method was used to measure total protein of 24 h urine,serum total protein,serum creatinine,total cholesterol and triglyceride.Elisa method was used to detect the serum ANGPTL4 level of rats.RT-PCR and Western blot technology were used to detect mRNA and protein expression of kidney tissue in rats.Results :Tenth days after PAN injection,levels of proteinuria in Pio0 and Pio4 group decreased significantly compared with PAN group [Pio0 group(16.08 ±3.50)vs(70.80±8.12)mg/24h;Pio4 group(33.81±4.16)vs(70.80±8.12)mg/24h;P<0.05].The expression of ANGPTL4 mRNA in renal tissue in Pio0 and Pio4 group showed a significant reduction(P<0.05)compared with PAN group,conversely the expression of serum ANGPTL4 increased significantly compared with PAN group [Pio0 group(104.11±10.56)vs71.90±14.91)ng/mL;Pio4 group(104.88±6.29)vs(71.90±14.91)ng/mL;P<0.05].Conclusion: PPAR gamma agonist may reduce proteinuria by increasing the serum expression of ANGPTL4 and reducing the expression of ANGPTL4 in renal tissue.