Effect Of PPAR-? Agonists On Serum Angiopoietin-like Protein 4 And Triglyceride In Rats With Nephrotic Syndrome

Objective: Hyperlipidemia is one of the main clinical features of nephrotic syndrome,usually manifested by elevated serum triglycerides,total cholesterol,and low-density lipoprotein cholesterol.The mechanism of hyperlipidemia in nephrotic syndrome is still unclear.Studies have found that impaired cholesterol clearance in nephrotic syndrome is due to the acquired lack of liver low-density lipoprotein receptors.However,there are relatively few studies on nephritic syndrome with hypertriglyceridemia.The main factor in regulating serum triglyceride levels is lipoprotein lipase(LPL)activity,LPL hydrolysis of triglycerides is free fatty acid(FFA),and enhance the absorption of FFA in the surrounding tissues,so LPL in the hydrolysis metabolism of triglycerides Play a decisive role.It was found that angiopoietin-like protein 4(ANGPTL4)can regulate lipid metabolism by inhibiting LPL activity,and that elevated ANGPTL4 in the circulation can reduce proteinuria.The peroxisome proliferator-activated receptor ?(PPAR-?)regulates the expression and production of ANGPTL4 in tissues.Therefore,the purpose of this study was to investigate the effect of PPAR-? agonist on serum ANGPTL4 levels and triglyceride levels in rats with nephrotic syndrome.Methods: Sixty male Sprague-Dawley rats were randomly divided into five groups: 1.Normal saline control group(n=15): intraperitoneal injection of an equal volume of saline and intragastrically administered with normal saline;2.PAN control group(n=15): A single intraperitoneal injection of puromycin aminonucleoside(PAN,150 mg/kg)was given by intragastric gavage;the other three groups were intragastrically administered with PPAR-? agonist pioglitazone(Pio,10 mg/Kg/day).therapy group.The specific groupings were as follows: 3.Pio-0 treatment group(n=15): intraperitoneal injection of PAN(150 mg/kg)and intragastric administration of pioglitazone on the day of injection;4.Pio-4 treatment group(n=10)): One-time intraperitoneal injection of PAN(150 mg/kg)and pioglitazone gavage treatment started 4 days after PAN injection;5.Pio-10 treatment group(n=5): single intraperitoneal injection of PAN(150 mg/kg),and Pioglitazone gavage treatment began 10 days after PAN injection.Rats in each group were harvested on the 4th,10 th and 21 th days after intraperitoneal injection of PAN,and 5 rats were harvested each time.The 24-hour urinary protein level was measured at each time point in each group;Serum triglyceride,total cholesterol,albumin,ANGPTL4,and LPL levels were measured at each time point in each group.Results:On the 4th,10 th,and 21 th days after intraperitoneal injection of PAN,urinary proteinuria was significantly higher in the PAN control group than in the saline control group(P<0.05).On the 10 th day after intraperitoneal injection of PAN,it was found that serum ANGPTL4 levels in rats treated with Pio-0 and Pio-4 were significantly higher than those in saline control group and PAN control group(P<0.05);Pio-0 and Pio-4 treatment groups Rat serum LPL was significantly lower than that of PAN control group(P<0.05);24-hour urine protein levels in rats treated with Pio-0 and Pio-4 were significantly lower than those in PAN control group(P<0.05);Pio-0 treatment group and The serum triglycerides in the Pio-4 treatment group were significantly higher than those in the PAN control group(P<0.05).Conclusions: PPAR-?agonist can up-regulate the expression and production of ANGPTL4 in serum of rats with nephrotic syndrome.The increase of serum ANGPTL4 can reduce the 24-hour urinary protein quantification and increase serum triglyceride levels.