The Effect Of Rosiglitazone Intervention On Renal Damage In Spontaneously Hypertensive Rats Induced By High-fat-high-glucose

Chronic renal injury is one of the target organs injuries induced by thehypertension. High-fat-high-glucose(HFHG) diet caused carbohydratelipid-derangement and energy dysfunction; induced Atherosclerosis;vascular diastolic function were attenuated; blood flow and Oxygensupply for the target tissue were reduced. Those effects were interactedwith these systems, such as Inflammation, oxidative stress, lipotoxicity andeventually they developed synergistic effect on the progressive renal injury.The damage or overexpression of the Endothelin played a role in thepathological progress. As vascular proconstriction, proliferation,profibrosis, platelets recruitment, thoses pleiotropic biological effects ofendothelins play a role in vascular constriction reaction, Ischemia anoxiainduced organs’ sclerosis. Endothelin-1acting via both endothelin receptorET-A receptor (ETAR) and ET-B receptor (ETBR). ETB serve a clearanceof ET-1concentrations. endothelial cell ETBR activation is vasodilatorymainly due to nitric oxide release.Thiazolidinediones (TZDs), like rosiglitazone and pioglitazone, areperoxisome proliferator-activated receptor PPARγ ligands, the ROSI couldexert effect on the renal injury prevention significantly. PPARγ directlybound to the PPARγ reaction element (PPRE) site between-1301and-1289in the5’-flanking region of human ETBR gene, that palys importantroles in improving vascular how the renal ETRB regulated by the ROSIand the effects of the renal functions remain further studies. A total of36male Spontaneous hypertensive rats (SHR), wererandomly divided into three groups:①treated group (R group, n=12),high-fat diet-fed ROSI (9mg/kg/day)-treated SHR;②control group (Hgroup, n=12), high-fat diet-fed SHR;③blank control group(C group,n=12),normal-fat diet fed SHR;The data revealed that:(1) compared withthe C group, at the end of the12thweek, the body weight of the H groupincreased (249.18±3.09g vs201.63±3.74g), the blood pressure(195.37±3.19mmHg vs175.49±2.82mmHg) arised respectively (P<0.05).The serum insulin levels increased significantly (79.61±3.16U/L vs54.61±4.33U/L, P<0.05), the HOMA-IR rosed remarkly (17.90±1.05vs12.18±1.17). The serum ET-1levels also increased (50.47±3.29pg/ml vs40.46±3.16pg/ml, P<0.05). and the Ccr reduced (5.75±0.66ml/min vs12.12±1.16ml/min)(P<0.01). ACR arised (0.80±0.04mg/μmol vs0.54±0.04mg/μmol，P<0.05). RT-PCR detected the renal local mRNAlevels, the ETRA and ET-1arised, and the ETRB and PPAR gammaadversed. The semiquantitative avaluated renal injury: GSI increased(1.85±0.32vs0.5±0.16); the TIS arised (2.8±0.23vs1.3±0.16);Our study reveal that,①C group, the body weight, lipidconcentration, insulin level, endothelin-1is steadly rising with the ages andthe blood pressure, as well as the aggravagated renal function, indicate thatboth ages and hypertension are take part in the gressively renal dysfuncionprogression.②insulin resistance index/hyperinsulin levels,endothelin-1levels of the H group is higher than that in the C group, demostrate the dietexacerbated the renal function.③above-mentioned parameter wereimproved insulin resistance in the R group, compared with the H group; butstill serious compared with the C group. The relevant mechanism is thatrosiglitazone attenuated ET-1–induced vasoconstriction through theupregulation of endothelial ETBR expression.