Effect Of Telmisartan On The Expression Of Adiponectin And Its Receptors, CRP, And TNF-a In Aortic Of Insulin Resistance Rats

Aim In order to offer some experimental evidences for the feasibility that telmisartan could be applied to prevent and treat IR, type 2 diabetes associated cardiovascular disease (CVD), the effect of telmisartan on the expression of adiponectin (APN) and its receptors, CRP, and TNF-αin aortic of IR rats was investigated, the relationship between this effect and inflammatory response in aortic of IR rats was explored.Methods Male SD rats were divided into four groups: control group, Tel group, IR group, IR+Tel group. Control group and Tel group were fed with ordinary diet for 12 weeks. Tel group rats were treated with telmisartan (5mg/kg/days,dissolved in drinking water) since the 4 weekend and administration lasted eight weeks. IR group and IR+Tel group rats were fed with high fructose diet for 4weeks to induce IR rats model. To verify IR rats model, the following indexs were measured respectively in each group: blood sample were withdraw from the end of tail of animals for fasting blood glucose (FBG) by automatic biochemical analyzer, fasting serum insulin (FSI) by radiotherapy immune act at 4 weekend, and insulin sensitive indexs (ISI) were calculated. When ISI≤-4.88 indicate modeling success. These rats which ISI≤-4.88 were selected as IR rats. IR group rats continued being fed with high fructose diet for 8 weeks.In addition to being fed with high fructose diet, IR+Tel group rats were treated with telmisartan (administration dosage and route was the same as Tel group) for 8 weeks at the same time. Systolic blood pressure (SBP) were measured at the end of weeks 0, 2, 4, 6, 8, 10, 12. FBG, FSI, and CRP were measured at the end of weeks 0, 4, 8, 12, and ISI were calculated. Fasting serum lipid level was measured by automatic biochemical analyzer and intraperitoneal glucose tolerance test was performed at 12 weekend. Animals were killed at the end of weeks 0, 4, 12, RT-PCR detected the expression of APN, AdipoR1, AdipoR2, CRP, and TNF-αmRNA in aortic.Results (1) Compared with the IR group, the SBP, CRP, FBG, FSI levels of the IR+Tel group decreased significantly(P<0.01); the ISI significantly increased(P<0.01); the fasting serum triglyceride (TG), total cholesterol (TC) contents of IR+Tel group decreased significantly (P<0.01); low density lipoprotein cholesterol (LDLC) content decreased too (P<0.05); high-density lipoprotein (HDLC) content significantly increased (P<0.01). (2) Compared with the control group, the expression of APN, AdipoR1. AdipoR2 mRNA was significantly reduced in aortic of IR group ( P < 0.01 ) , and TNF-α,CRP mRNA expression was significantly increased(P<0.01); Compared with the IR group , the expression of APN, AdipoR1 and AdipoR2 mRNA in aortic of IR+Tel group was significantly increased(P<0.01), the expression of TNF-α,CRP mRNA was significantly reduced (P<0.01).Conclusion 1. Telmisartan can reduce the SBP, correct glucose and lipid metabolism, increase insulin sensitivity and improve IR of IR rats. 2. Telmisartan can increase the expression of anti-inflammatory factor APN and its receptors AdipoR1,AdipoR2 mRNA in aortic of IR rats; reduce the expression of inflammatory cytokines CRP, TNF-αmRNA in aortic of IR rats. These results suggested that telmisartan may inhibit inflammatory response in aortic of IR rats.