| 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 IL-6, IL-18and TLR4in OLETF rats with insulin resistance;2. To observe change of TLR4in myocardial tissue in every group;3. To study the possible mechanisms of the pioglitazone and metformin reducing the risk of cardiovascular diseases.4. To study the differences of the pioglitazone and metformin in promoting IR and protecting the cardiovascular system.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 for12hours, the plasma levels of FINS, FBG were evaluated, and HOMA-IR and IS I 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 O), in which the rats were fed with high-fat diet; the Pioglitazone group(group P), in which the rats were fed with high-fat diet and Pioglitazone(2mg/kg·d), the Metformin group (group M), in which the rats were fed with high-fat diet and Met (150mg/kg·d),. The12LETO rats fed with normal diet served as normal control group (group NC). After20weeks of drug intervention, fasted12hours 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 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 SPSS19.0statistical 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 O (P<0.05),and the ISI was obviously lower, the differences were obvious; comparing with group O, the FBG, FINS、HOMA-IR were significantly decreased in group P and group M, and the ISI was obviously higher (P<0.05), 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 O(P<0.05), the HDL-C was obviously lower, the differences were obvious; comparing with group O, the TC, TG, LDL-C were significantly decreased in group P and group M, the HDL-C was obviously higher, the differences were obvious (P<0.05)3. Comparisons of levels of serum IL-6, IL-18, TLR4among every group: Comparing with group NC, the level of serum IL-6, IL-18, TLR4were significantly increased in group O (P<0.05), the differences were obvious; comparing with group O, the level of serum IL-6, IL-18, TLR4were significantly decreased in group P (P<0.05), the differences were obvious; comparing with group O, the level of serum IL-6, TLR4were significantly decreased in group M, the differences were obvious, but the differences of IL-18were not significantly obvious (P>0.05)4. Expression of TLR4in myocardial tissues among groups:Comparing with group NC, the relative amounts protein of TLR4were higher in group O (P<0.05) the differences were obvious; comparing with group O, the relative amounts protein of TLR4were decreased in group P and M (P<0.05), the differences were obvious.Conclusion:1.Comparing with group NC, the level of FBG, FINS, HOMA-IR, TC, TG, LDL-C, IL-6, IL-18and TLR4were significantly increased in OLETF rats fed with high-fat diet, but HDL-C and ISI were significantly decreased.2. the pioglitazone and metformin can improve IR through decreasing the level of FBG, FINS, TC, TG, LDL-C, and increasing the level of HDL-C.3. the pioglitazone and metformin may protect the cardiovascular system by inhibiting the expression of TLR4in myocardial tissues.4. In addition, comparing with metformin, the pioglitazone still can significantly reduce the level of serum IL-18, this result showed that pioglitazone can be better than metformin in improving IR. |
PDF Full Text Request