The Effects Of 2,3,7,8-Tetrachlorodibenzo-p-dioxin On The Glucose And Lipid Metabolism Of High-fat Fed Rats

Backgrouds W ith the devlopment of industriy, there are some of new chemistriy is creasing ,the enviroment pullution Stained so more serious that the hume health get m -ore attention . Dioxin is a typical one of the persistent organic pollutants, chlorinated dioxins is by- products of chlorinated organic combustion and chlorinated industrial in the 20th century, for the chlorinated tricyclic aromatic compounds, containing a total of 210 compounds The most toxic is 2,3,7,8 - tetrachlorodibenzo-dioxin (TCDD), a l- ipophilic, biodegradable, bioaccumulation and other properties of lead in the human for a long time. increased food intake, particularly from a high-fat diet (HFD), may also increase risk of dioxin toxicities through higher intakes of TCDD. Furthermore, elimination of TCDD is slowed significantly with increasing adiposity, increased the toxicity of TCDD, such as endocrine-disrupting toxicity. therefore TCDD and other endocrine disruptors more vulnerable to Interfere of high fat diet.high fat diet increas ed triglycerides or fatty acid deposition in peripheral, so that excessive fat tissue imb- alance of endocrine signals, induce insulin resietance.Objective we give different doses of TCDD in high fat rats in order to observe the joint toxicity, namely, to observe the glucose metabolism and lipid metabolism and to explore some mechanisms to provide some theoretical basis of the reasons for diabetes , to support the previous epidemiological observations on the relationship between TCDD exposure and occurrence of metabolic disorders including diabetes mellitus.Methods①40 male SD rats were randomly divided into control group (NC group, n = 10) and high fat diet group (HF group, n = 30), NC group were fed basal diet, HF high fat diet group was given 6 weeks. High-fat high-fat fed rats were randomly divided into control group (HF group), a small dose of TCDD group (0.4μg/kg), the dose of TCDD group (1.6μg/kg), high dose of TCDD group (6.4μg/kg), TCDD dose group (25.6μg/kg).then the rats of high fat recived loading dose rates (LDRs) of 0.4, 1.6, 6.4, or 25.6μg/kg b.w intraperitoneally (i.p.) All animals were weighed every two days, and feed intake was recorded and adjusted for spillage.②we Implementation of the intraperitoneal glucose tolerance test on the Ninth week, collect the blood of each group to analyze for glucose, insulin, triglyceride, cholesterol changes on the tenth week, eleven weeks respectively.we killed the rats then taken the liver tissue specimens to paraffin sections for HE staining and frozen sections were stained with oil red.④Extraction of liver mRNA, observed Insig-1, PGC-1αand Lpin-1 gene changes. in each group.Results 1.Experiment sixth week, compared with NC group, HF rats, body weight (body weight, BW) significantly increased, with significant difference. Fasting insulin (fasting plasma insulin, FIN), fasting blood glucose (fasting plasma glucose), triglyceride (triglyceride TG), total cholesterol(totalcholesterol, TC) has increased, but no significant difference.2.Experimental ninth week (third week after administration), compared with NC group, HF rats, blood glucose at 30min, 60min, 120min increased, with statistically significant (P <0.05); HF +0.4μg / kg, HF +1.6μg / kg blood glucose at 0min, 30min, 60min, 120min increased, with statistical significance (P <0.05); HF +6.4μg / kg blood glucose at 30min, 120min increased with significant (P <0.05); HF +25.6μg / kg increased blood glucose at30min statistically significant (P <0.05). Compared with the HF, HF +0.4μg / kg blood glucose at 0min, 30min, 60min, 120min increased, with statistical significance (P <0.05); HF +1.6μg / kg blood glucose rise at 30min high with statistical significance (P <0.05). Compared with the HF, HF +0.4μg / kg on the tenth week, blood glucose increased, with statistical significance (P <0.05), while the eleventh week increased, but no statistically significant (P> 0.05 ); HF +25.6μg / kg group on the tenth week, the blood glucose decreased significantly (P <0.05); other dose groups no significant difference in blood glucose(P> 0.05).3.Compared with NC, HF group, HF + TCDD, respectively, each dose insulin in the ninth week, the tenth week, the eleventh week of increases, with statistically significant (P <0.05). Compared with the HF, HF + TCDD insulin each dose group was no significant difference(P> 0.05).4.Compared with the NC ,HF group, HF + TCDD dose group rats of the triglycerides has increased in the ninth week, but no statistical significance; HF group, HF + TCDD dose group of the TG has increased in the tenth week, in the eleven week , with statistical significance (P <0.05). Compared with the HF, HF +0.4μg / kg, HF +1.6μg / kg, HF +6.4μg / kg group rats of triglycerides was significantly higher in the tenth week, there was statistically significant (P <0.05), howerve The eleventh week of its level decreased gradually, no statistically significant (P> 0.05).5.Compared with NC, HF group, HF 0.4μg/kg group of cholesterol in the ninth week, tended to increase but no statistically significant (P> 0.05), while in the tenth week, the tenth week was significantly higher , With statistical significance (P <0.05); HF 1.6μg/kg, HF 6.4μg/kg,HF 25.6μg/kg group were increased in the above mentioned period, with statistically significant (P <0.05). Compared with the HF, HF +0.4μg / kg of cholesterol in these rats tended to increase at each time point, but no statistically significant (P> 0.05); HF +1.6μg / kg, HF +6.4μg / kg, HF +25.6μg / kg of cholesterol in these rats was significantly higher at each time point, and was statistically significant (P <0.05).6. HE liver tissue and oil red staining: all the TCDD dose groups show of the fatty degeneration of the liver significantly and dose-dependent.7. compared with the NC, HF rat mRNA expression of liver Insig-1, PGC-1α, Lpin-1 gene transcription levels were reduced by 30%, 25%, 14% respectiy, compared with the HF, HF +0.4μg / kg group rats mRNA expression of liver Insig-1, PGC-1α, Lpin-1 gene transcription levels were reduced 25%, 25%, 33%, HF +1.6μg / kg group liver Insig-1, PGC-1α, Lpin-1 gene transcription levels were reduced 30%, 29%, 39%; HF +6.4μg / kg group liver Insig-1, PGC-1α, Lpin-1 gene transcription levels were decreased by 45%, 43%, 54% ; HF +25.6μg / kg group liver Insig-1, PGC-1α, Lpin-1 gene transcription levels were decreased by 53%, 55%, 56%.8.compare of the NC group, HF group, HF +0.4μg / kg, HF +1.6μg / kg body weight significantly increased , with statistically significant (P <0.05); HF group +6.4μg / kg body weight caused reduced gain in body weight, tending to be close to the normal controls after day 10, However, LDR of 25.6μg/kg TCDD caused reduced gain in body weight, which was significantly lower than normal controls after day 17. with a statistically significant difference (P <0.05).Compared with the HF, HF +0.4μg / kg group, HF +1.6μg / kg body weight has no significant increase in rats; HF +6.4μg / kg, HF +25.6μg / kg group lost weight, respectively, in the first 20 days and 12 days with a statistically significant difference (P <0.05).Compared with HF, high-dose TCDD group reduced their food intake, a large dose of TCDD significantly inhibit appetite, from the first administration on 5th days with significant difference (P <0.05).Conclusion 1. fat diet on the serum total cholesterol, triglycerides, fasting serum insulin, glucose increased .2. on the basis of the high-fat diet, TCDD interferes with glucose metabolism, affecting glucose tolerance, but with time-dependent and dose-related.3.TCDD interfere with lipid metabolism in rats with high fat diet, resulting in the formation of fatty liver, and relative with liver Insig-1, PGC-α, Lpin-1 gene low expression.4. Large dose of TCDD change high fat rats weight is correct with inhibite of food intake.