Effects of tesaglitazar on serum nitric oxide and heart type inducible nitric oxide synthase mRNA expression in diabetic mice / 医学研究生学报

ABSTRACT

Objective Recent studies show that, tesaglitazar can reduce vascular plaque lipid deposition and inflammatory response in mice.This paper aims to investigate the effects of tesaglitazar, the peroxisome proliferator-activated receptor α/γ( PPARα/γ) agonist on serum lipid, serum nitric oxide ( NO) and heart type inducible nitric oxide synthase ( iNOS) mRNA expression in diabetic mice. Methods Thirty female 3-week-old clean grade mice were fed with ordinary adaptive diet for 7 days.The diabetic mouse model was established by feeding these mice with high-glucose-high-fat diet for four weeks and then taking small doses of streptozotocin( STZ) .These mice were randomly divided into two groups by means of ran-dom number tablecontrol group and tesaglitazar group.Control group continued to be fed with high-glucose-high-fat diet, whereas te-saglitazar group was administered with tesaglitazar orally( high-glucose-high-fat fodder mixed with 20μg/kg tesaglitazar) .After 6 weeks′administration, body weight, total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipo-protein cholesterol(HDL-C) and blood glucose(Glu) levels were measured.Serum NO content were detected with nitrate reductase method, and the expression of iNOS mRNA in heart were detected by RT-PCR. Results Compared with control group[(3.62 ± 0.45)、(2.58 ±0.34)、(1.35 ±0.26)、(19.55 ±3.40) mmol/L], serum levels of TC、TG、LDL-C and Glu in tesaglitazar group [(2.93 ±0.38)、(1.87 ±0.41)、(1.07 ±0.30)、(14.33 ±2.08)mmol/L] were significantly decreased, difference was statistically significant(P<0.01).However, the levels of HDL-C were increased obviously campared with the control group[(1.32 ±0.21) mmol/L vs (1.05 ±0.24)mmol/L, P<0.01];The serum NO content in control group were significantly higher than that in tesaglita-zar group[(75.60 ±8.06)μmol/L vs (41.35 ±5.82)μmol/L] , difference was statistically significant(P<0.01); The ralative quantitative expression of iNOS mRNA in treatment group was significantly lower than that in control group[(0.435 ±0.064) vs (0.568 ±0.067)], difference was statistically significant(P<0.01). Conclusion Tesaglitazar can reduce the production of NO by means of inhibit excessive expressions of iNOS mRNA in diabetic mice.It can also improve the levels of serum lipid, and can delay the progression of atherosclerosis.