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Background and purpose of type 2 diabetes and atherosclerosis, hypertension, dyslipidemia and vascular abnormal response to insulin is associated with an insulin resistant state. We can replicate this model for high-fructose diet. Arachidonic acid (AA) is the human body a variety of important cardiovascular precursor of the active substance, its metabolites on the cardiovascular system has a significant protective effect, including as a hyperpolarizing factor vasodilator, nitric oxide synthase increased protection vascular endothelial cells, anti-inflammatory, anti-apoptosis and promoting angiogenesis, many effects through the activation of phosphatidylinositol 3-kinase (phosphatidylinositide-3kinase, PI3K) and mitogen-activated protein kinase (mitogen-activated protein kinase, MAPK) signaling mediated by the channel, which both are important insulin signal transduction pathway. Nitric oxide (NO) is the body molecules important biological information, skeletal muscle insulin mediated by NO vasodilation, thus blood flow, promoting glucose uptake, to improve skeletal muscle insulin resistance in peripheral tissues and organs. So arachidonic acid oxidase cytochrome p450 table (CYP) metabolites (EETs) for hypertension and diabetes and insulin resistance treatment effect how? Its associated signal transduction pathway molecule is changed, whether involving nitric oxide synthase activity change it? article mild hypertension in fructose-induced rat model of insulin resistance genes studied CYP2J3 blood pressure and insulin resistance in its therapeutic effect and its mechanism. Methods Male Sprague-Dawley (SD) rats (n = 21) 10% fructose drinking water (fructose) 4 周 induce the formation of mild hypertension and insulin resistance in animal models were randomly divided into three groups: fructose-drinking group (F , n = 7), fructose water plus CYP2J3 (F 2J3 group, n = 7), fructose CYP2J3 plus water plus nitric oxide synthase inhibitor L-NAME (F 2J3 L group, n = 7). The blood pressure measuring blood pressure meter, once a week, 4 weeks and fructose-induced gene therapy specimens from the second week after the rat tail vein and 24-hour urine sample, standard methods of clinical serum lipids, serum insulin, glucose. Germany Gonotec osmomat 030 type measured osmolality urine osmolality. Insulin resistance index (IR) technology by homeostasis model (HOMA) calculated: HOMA-IR = [fasting plasma insulin (μU / ml) × fasting glucose (mmol / L)] / 22.5 (HOMA-IR = FINS × FBG / 22.5). Animals were sacrificed at 2 weeks, RT-PCR assay rats in each group before and after gene therapy for aortic ET-1, ETA-R expression; Western blot analysis of liver CYP2J3 protein, eNOS protein, MAPK and AMPK signaling channel protein expression . Results after 4 weeks of high fructose water, animal blood, serum insulin levels were significantly higher than the normal amount of urine drinking group, urine osmolality was significantly lower than normal water animals. F 2J3 1 week after intervention group had significantly decreased systolic animals (reduced by the 115.2 ± 6.1 112.4 ± 2.6 mmHg), maximum antihypertensive effect in the first two weeks after the gene introduction (108.16 ± 3.6 mmHg), and the difference between Group F There was significant (p lt; 0.05), the antihypertensive effect lasts for 3 weeks. In the F 2J3 L-NAME group 1 week after intervention blood pressure rapidly increased to 135.7 ± 2.3 mmHg, and F, and F 2J3 group were statistically significant (p lt; 0.01), completely blocked the antihypertensive 2J3 role in the first two weeks continued to rise to 146.3 ± 5.2 mmHg, and group F group and FJ extremely statistically significant (p lt; 0.01), the first three weeks continued to show a rising trend. And the drop in blood pressure, while plasma insulin concentrations, insulin resistance index also decreased urine osmolality was significantly elevated, but these effects are L-NAME blocked. CYP2J3 gene after two weeks, F 2J3 group and F 2J3 L-NAME group liver CYP2J3 protein expression was significantly higher than the F group. Western blot analysis of two sets of genes injected CYP2J3 CYP2J3 protein expression in liver tissue were higher than group F; F 2J3 group liver eNOS, phosphorylated MAPK and phosphorylated AMPK protein expression was significantly higher than the F group, plus L-NAME group of three proteins significantly reduced, MAPK, and total protein content of AMPK was no significant difference between the three groups. Conclusion animal drinking water can lead to high blood pressure high fructose and hyperinsulinemia, and its mechanism may be related to vascular ET-1, ETA-R upregulation, eNOS protein decreased, MAPK, AMPK and other signaling channel protein downregulation, CYP2J3 possibly through the introduction of genes reduced vascular ET-1 and ETA-R mRNA expression in the liver increased eNOS protein, MAPK, AMPK channel proteins to improve insulin resistance and lower blood pressure, the results suggest CYP2J3 gene therapy of diabetes or insulin resistance, especially patients with hypertension by increasing NO achieved. This is insulin resistance and hypertension treatment provides a new strategy, and gradually reveal the underlying mechanism.
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