The Effect Of Telmisartan On The Liver Macrophage Polarization Of The Rats Fed With Long-term HSHF Diet

Objective:1.To observe the effects of telmisartan on fasting plasma glucose(FPG),fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)in long-term high sugar and high fat(HSHF)dietary rats.2.To observe the effect of telmisartan on the liver pathomorphism and macrophage polarization of liver in long-term HSHF-fed rats and to explore the possible mechanism of telmisartan in improving insulin resistance in long-term HSHF-fed rats.Methods:The healthy male SD rats were randomly divided into two groups: control group(n =10),fed with normal diet of Shanxi Medical University Animal Experimental Center;high-sugar and high-fat group(n = 20),fed with high-sugar and high-fat diet,which our team had used for several times,the formulations are as follows: 70% of ordinary feed(fabric,provided by Shanxi Medical University Animal Experimental Center)+ 20% lard +10% sucrose + 1% cholesterol + 0.25% cholic acid.The rats in both groups were fed and drunk with water before dark.The 20 survived rats in the HSHF group was randomly divided into two subgroups after 6 months: the HSHF diet group(HSHF group,n=10)was fed with the high sugar and high fat diet.The high sugar and high fat diet and telmisartan Group(telmisartan group,n=10)receiving the high-sugar and high-fat diet feeding while telmisartan 5mg / kg.d gavage at the same time.Rats in the control group,HSHF group and telmisartan group were fed for the next 3 months.At last,there are 9,8,9 rats left in the control group,HSHF group and telmisartan group.We chose 6 rats in the survived rats randomly in each group.These rats were fasted for 8 to 12 hours.Then,the rats were weighed and intraperitoneally injected with urethane(4 ml/kg).After anesthesia,the samples were took out and stored in a sterile EP tube after centrifugation(3000r/min15min).The specimens were stored in a refrigerator at-70 ?,and then the FPG and FINS were measured,the HOMA was calculated(HOMA-IR = FPG(mmol / L)xFINS(?IU/ mL)/22.5).Two rat livers were took out under sterile conditions,one liver was took for pathological paraffin section,stained with hematoxylin-eosin(HE),liver tissue pathology examination.The other liver was labeled and rapidly put into liquid nitrogen.Western blot was used to detect the expression of M1 macrophage markers(iNOS)and M2 macrophages markers(Arg-1)in the liver.Results:1.Compared with the control group,FPG,FINS and HOMA-IR in the HSHF group are significantly higher(P <0.05).Compared with the HSHF group,FPG,FINS and HOMA-IR are significantly decreased in the telmisartan group(P <0.05).2.Compared with the control group,the liver HE staining results in the HSHF group indicate that the liver are visible diffuse fatty degeneration,the nucleus are located in the edge,most of the cells are vacuolated,the volume of liver cell increases significantly,macrovesicular lipid droplets deposit in the cytoplasm,ballooning degeneration become common,cytoplasm rarefaction,a large number of inflammatory cells infiltrate in the hepatic lobule and portal area and spotty necrosis are common.Compared with the HSHF group,the liver HE staining results in the telmisartan group indicate that the volume of the liver cells and the lipid droplets are reduced,ballooning degeneration and inflammation of were significantly improved.3.Compared with the control group,the expression of iNOS protein in the liver of HSHF group is significantly higher than that in control group(P <0.05).Compared with HSHF group,the expression of iNOS protein in telmisartan group is significantly lower than that in HSHF group(P <0.05).4.Compared with the control group,the expression of Arg-1 protein in the liver of HSHF group is significantly lower than that of the control group(P <0.05).Compared with HSHF group,the expression of Arg-1 protein in the liver of telmisartan group is significantly lower than that in HSHF group(P <0.05).Conclusions:1.Telmisartan reduces the levels of FPG and FINS in long-term HSHF dietary rats and improves the status of insulin resistance.2.Telmisartan not only reduces the fat content and inflammatory cell infiltration significantly,but also reduces the marker of M1 macrophages and increase the marker of M2 macrophages in the liver of long-term HSHF-fed rats.It,s mechanism of improving insulin resistance may be related to the state of the macrophage polarization in the liver.