| Objective:Through feeding otsuka long-evans tokushima fatty (OLETF) rats with high-fat diet to establish the insulin resistance model, the purposes of this study is:1.To observe change of interleukin-18(IL-18) in OLETF rats with insulin resistance;2. To observe change of Toll like receptor4in circulation and myocardial tissue of all the rats in every group;3. To study the effect of angiotensin II type1receptor antagonists (AT1R) telmisartan on insulin resistance and the expression of IL-18;4.To study the effect of peroxisome proliferator-activated receptor y (PPAR-y) pioglitazone on the expression of TLR4, and the possible mechanisms of the pioglitazone reducing the risk of cardiovascular diseases.Methods:36OLETF rats and the fellow12long-evans tokushima otsuka (LETO) rats which were4weeks old fed with normal diet to adapt to environment. At eight weeks old, the OLETF rats began to be fed with high-fat diet. Twenty weeks later, the rats of every group fasted for14hours, the plasma levels of FINS, FBG were evaluated, and HOMA-IR and ISI were measured, which to determine whether the IR model was successfully established. All the OLETF rats with insulin resistance were randomly divided into3groups:the model group(group M), in which the rats were fed with high-fat diet; the telmisartan group(group T), in which the rats were fed with high-fat diet and telmisartan(5mg/kg· d); the Pioglitazone group(group P), in which the rats were fed with high-fat diet and Pioglitazone(2mg/kg· d). The12LETO rats fed with normal diet served as normal control group (group NC). After20weeks of drug intervention, fasted14hours again, the plasma levels of FINS, FBG, triglycerides (TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol (LDL-C), IL-18and TLR4were detected in four groups, then all the rats were killed, and Store the myocardium, pancreas, kidneys and other tissues of all the rats at-80℃refrigerator. Detect the expression of TLR4in myocardial tissues by Western Blotting. All the results were analyzed and processed by SPSS20.0statistical software.Results:1.Comparisons of FBG, FINS, HOMA-IR and ISI among every group: Comparing with group NC, the FBG, FINS, HOMA-IR were significantly increased in group M(P<0.05or P<0.01),and the ISI was obviously lower, the differences were obvious; comparing with group M, the FBG, FINS、HOMA-IR were significantly decreased in group T and group P, and the ISI was obviously higher (P<0.05or P<0.01), the differences were obvious.2. Comparisons of data of lipid metabolism among every group:Comparing with group NC, the TC, TG, LDL-C were significantly increased in group M (P<0.05or P<0.01), the HDL-C was obviously lower, the differences were obvious; comparing with group M, the TC, TG, LDL-C were significantly decreased in group T, the differences were obvious (P<0.05or P<0.01); comparing with group M, the TC, TG, LDL-C were significantly decreased in group P, the HDL-C was obviously higher, the differences were obvious (P<0.05or P<0.01)3. Comparisons of levels of serum IL-18, TLR4among every group:Comparing with group NC, the level of serum IL-18, TLR4were significantly increased in group M (P<0.05or P<0.01), the differences were obvious; comparing with group M, the level of serum IL-18, TLR4were significantly decreased in group T and group P (P<0.05or P<0.01), the differences were obvious.4. Expression of protein of TLR4in myocardial tissues among groups: Comparing with group NC, the relative amounts protein of TLR4were higher (P<0.05), the differences were obvious; comparing with group M, the relative amounts protein of TLR4were decreased in group T and P (P<0.05or P<0.01),the differences were obvious.5. Correlation analysis between IL-18, TLR4and HOMA-IR:Pearson correlation analysis showed that IL-18, TLR4had positive relationship with HOMA-IR. 6. The multiple regression analysis showed that IL-18and TLR4were the independent factors affecting HOMA-IR.Conclusion:1.The level of FBG, FINS, HOMA-IR, TC, TG, LDL-C, IL-18, TLR4were significantly increased in OLETF rats fed with high-fat diet, but HDL-C and ISI were significantly decreased.2. With the treatment of telmisartan, the level of FBG, FINS, HOMA-IR, TC, TG, LDL-C, IL-18, TLR4were significantly decreased, ISI was significantly increased. The results showed that telmisartan can improve insulin resistance by regulating blood glucose and serum lipid as well as inhibiting the expression of IL-18.3. With the treatment of pioglitazone, the level of FBG, FINS, HOMA-IR, TC, TG, LDL-C, IL-18, TLR4were significantly decreased, ISI and HDL-C were significantly increased. The results showed that pioglitazone can significantly improve insulin resistance,4. In addition, pioglitazone can significantly reduce the expression of protein of TLR4in myocardial tissues. This result showed that pioglitazone can reduce the risk of cardiovascular diseases by inhibiting the expression of TLR4. |
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