| Objective:1.To investigate effect of pioglitazone on expression of TLR-4,NF-κB,MCP-1indiabetic rats aorta.2.Pioglitazone intervention for the expression of diabetes rat thoracic aorta tissueTLR-4, NF-κB,MCP-1.Methods:50male SD rats were randomly divided into NC group(n=10)and modelgroup(n=40). The two groups were fed with standard chow, HSFDs respectively. AfterHSFDs fed for4weeks，blood samples from rat were collected and the FBG,TC, TG,LDL-C, HDL-C, FINS level were assayed.After4weeks,the two groups were injected intraperitoneally with STZ,citrate bufferby35mg/kg respectively after fasting for12hours. After72hours, the mouses werediagnosised with diabetes, if the random blood glucose of them was higher than16.7mmol/L for three consecutive days. Then they were grouped into four groups:group DM(10mg.kg-1.d-1physiological saline,n=10),group A(pioglitazone2.5mg.kg-1.d-1,n=10), group B (pioglitazone5mg.kg-1.d-1, n=10), group C(pioglitazone10mg.kg-1.d-1,n=10). Pioglitazone was solubled in and filled into stomach at9:00AM daily. The ratsof group DM were given10mg.kg-1.d-1physiological saline.The rats of NC groupwere fed with the standard chow, while the remaining four groups were fed with thehigh fat diets.BW,FBG,FINS,TG,TC,LDL-C,HDL-C were measured after12weeks.The morphological changes of aorta tissues were observed through lightmicroscopy after HE staining. Immunohistochemistry staining was used to examine theexpression of TLR-4,NF-κB,MCP-1protein in the aorta. The expression of TLR-4mRNA was detected by RT-PCR.Results: 1. After four weeks, compared with group NC,BW,FBG,FINS,TG,LDL-C of therats in model group were much higher(P<0.01), and the TC, HDL-C were no statisticaldifference (P>0.05).2.After12weeks,Compared with group NC, FBG,TG,TC, LDL-C in group DM andgroup A,B,C were significantly higher (P<0.05),BW,FINS,HDL-C in group DM andgroup A,B,C were significantly lower(P<0.05).FBG,TG,TC,LDL-C in group C wassignificantly lower than that in group DM(P<0.05).BW,FINS in group C wassignificantly higher than that in group DM(P<0.05);TC,HDL–C were no statisticaldifference between group DM and group C (P>0.05).3. The structure of endotheliocyte in rat′s aorta of group NC was clearly, endothelialcells without shedding, mitochondrial was in good codition and the ridge was clear;Intima was smooth, vascular smooth cells and outer loose connective tissue werenormal. The endotheliocytes in rat′s aorta of group DM have been partly damaged，theelastic lamina was asymmetric thickness and some had fissures and disruptions. TheSMCs had slight proliferation and disorganized arrangement. And the lesions in rat′saorta of group C with drug intervention was significantly lighter than DMgroup.Although the pathological changes in rat′s aorta of group A and B was lighterthan that of Group DM, it was not so obviously as compared to group C.4.There is little expression of TLR4,NF-κB,MCP-1in rats of group NC.Comparedwith group NC, the expression of TLR4,NF-κB,MCP-1was significantly increased ingroup DM(P<0.05),and the positive cells presented yellow in nucleus.And itsexpression in the same area of thoracic aorta in rats of group C was weak positive,compared with the group DM, the difference was statistically significant（P<0.05;Compared with group DM,the expression of TLR4,NF-κB,MCP-1in rats ofgroup A was significantly weaked (P<0.05); The staining of TLR4, NF-κB, MCP-1inGroup A was increased significantly compared to that of Group C (P <0.05); That ofGroup B was between group A and group C.5. RT-PCR analysis of the expression of TLR4mRNA in rat thoracic aorta,Theexpression in the NC group was weaker, The expression of TLR-4mRNA in group DM was significantly higher than that of the other four groups（group A,B,C,NC）（P<0．05）; The expression of TLR4mRNA in groups with Pioglitazone intervention isgroup A,B,C from stong to weak, and the difference between each two groups wasstatistically significant (P <0.05).Conclusions:1.The expression of TLR-4,NF-κB,MCP-1in aorta is increased in rats with diabetics,suggesting that TLR-4may take part in the pathogenesis of diabetics macroangiopathy.2. Pioglitazone may reduce the expression of TLR4, NF-κB,MCP-1in the aorta ofrats with diabetics, and protect the aorta of rats with diabetics via reducing its anti-inflammatory activity. |
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