Effect Of Pioglitazone On Liver And Expression Of Nuclear Factor-kappa B And Monocyte Chemoattractant Protein-1in Type2Diabetic Rats

Objective To observe the effect of pioglitazone on liver constitution andfunction、 NF-κB（nuclear factor-κB，NF-κB）、monocyte chemoattractant protein-1 (MCP-1) level in the serum and urine, the liver expression of NF-κB and MCP-1inType2diabetic mellitus(T2DM) rats,and investigate its possible liver protectivemechanisms in type2diabetic mellitus(T2DM) rats.Methods To divide the SD rats into two groups,the normal control group (NCgroup=10) fed with normal diet. The model of T2DM ra（tn=25）was established by fedwith high-sucrose-high-fat diet and injected low dose of strep tozotocin (STZ). Afterthree months,20successful T2DM rats were random diveded into DM group (n=10) andPIO group(n=10).for the pioglitazone (PIO) group, the T2DM rats received PIOintervention.After8weeks,serum and urine were collected, fasting insulin(FINS)、triglyceride(TG）、cholesterol(TC）、fasting peripheral blood glucose(FBG)、glycosylatedhemoglobin A1c(HbA1c)、alanine aminotransferase（ALT）、urinary albumin/creatinineratio(ACR)、urinary retinol binding-protein(URBP) were examined,；NF-κB、serummonocyte chemoattractant protein(SMCP-1)、 urinary monocyte chemoattractantprotein-1(UMCP-1) was also detected. To obtain the liver sample, observing pathologicchanges via light microscope, partly for examining the expression of MCP-1,NF-κBprotein by histochemical staining.and detecting expression of MCP-1,NF-κB mRNA byRT-PCR.Results1. The levels of FBG and HbA1c in group DM and group PIO were significantlyhigher compared with those of group NC(P<0.01),and there were no statisticaldifferences between group DM and group PIO (P>0.05);Level of FINS in group PIOwas significantly lower than those in the DM group（P<0.05);but there was nosignificant difference between in the PIO group and NC group（P>0.05).2. TC and TG level in groups DM and group PIO increased significantly comparedwith those in group NC (P<0.01).Treatment with pioglitazone significantly reducedthe TC and TG (P<0.01). Level of ALT in group DM was significantly increased than those in the NC group（P<0.05);but there was no significant difference betweenin the PIO group and DM group（P>0.05).3. NF-κB,SMCP-1level,UMCP-1excretion rate,ACR and URBP excretion rate ingroups DM and group PIO increased significantly compared with those in group NC(P<0.01). Treatment with pioglitazone also significantly reduced NF-κB, SMCP-1level, UMCP-1excretion rate, ACR as well as URBP excretion rate (P<0.01). Inaddition, UMCP-1excretion rate, NF-κB and SMCP-1level respectively showedpositive correlations with ACR, URBP excretion rate.4. The expression level of MCP-1,NF-κB protein in liver tissue in group DM andgroup PIO was significantly higher (P<0.01)than that in group NC, pioglitazone caninhibit the expression of MCP-1、NF-κB protein(P<0.01).5. The light microscopes results showed that there’s no pathological lesion (fattydegeneration and fibrosis)of liver found in group NC. Pathological changes weremuch more obvious in group DM. It was clear that the structure of liver weredestroying, it were evaluated that severe fatty degeneration and fibrosis.Pathologicalchanges in group PIO were lighter, it can be observed that liver was constrictiveslightly,it were evaluated that mild fatty degeneration and fibrosis.Conclusion The lever of NF-κB、MCP-1were reduced by pioglitazone in serum andurine of T2DM rats,and alleviated pathological damage,such as fatty degeneration andfibrosis.It has some protective effect on type2diabetic rat liver, and this protectiveeffect is independent on the hypoglycemic effect. The mechanism may be related withits inhibition effect on NF-κB、MCP-1protein expression in liver,reduce the lever ofNF-κB and MCP-1in serum.