| Obesity is a condition of excessive weight, especially related to excess of triglyceride accumulation. Obesity does not simply mean overweight, which more emphasizes on the state of accumulation of excessive fat in the body. Excessive fat accumulation is the result of an imbalance between energy intake and energy output, or abnormal metabolism, which results in excessive growth of body weight, increased adipose tissue, even pathology or physiological changes. Obesity is usually associated with insufficient physical activity, genetic predisposition, and individual behavioral factors, as well as gender and age. The prevalence of obesity is at an epidemic proportion in modern society, and it is accompanied by an increase in morbidity and mortality from cardiovascular diseases, including atherosclerosis. As we all know, blood vessel is an important channel to transport nutrients and discharge the waste. Integral and healthy vessel ensures the supply of adequate blood containing oxygen and nutrients to corresponding tissues and organs, as well as the timely excretion of metabolic waste. Therefore, improved vascular function has very important significance on local organs even the whole body. While vascular function is mainly dependent on a series of vasoactive factor secreted from vascular endothelial cells. Among these endothelial factors regulating vascular contraction and relaxation, the most important one is nitric oxide(NO). NO is synthesised from the amino acid L-arginine by a family of enzymes known as nitric oxide synthase(NOS). Its main function is to maintain vascular diastolic, inhibit adhesion of leukocyte, reduce proliferation of vascular smooth muscle cells. Based on variety of pharmacological effects, NO could prevent atherosclerosis and thrombus formation. The NOS enzyme occurs as three isoforms, namely neuronal NOS(n NOS), inducible NOS(i NOS) and endothelial NOS(e NOS). Of the three isoforms, it has been proposed that e NOS is the major isoform responsible for NO production under physiological conditions in the cardiovascular system and endothelial cells in particular. Followed by the injured synthesis and release of NO, endothelial function was impaired.With the development of science and technology, a large number of micro RNA is found distribution in a number of diseases, which has gradually attracted people’s attention. A lot of studies show that micro RNA is widely involved in the regulation of physiological and pathological changes, including obesity. In obese patients, many micro RNA express, which causes body injury.Micro RNA-27 a is one of them. It increases in obese rats or obese patients and negatively regulates adipocyte. Some studies have also found that the expression of micro RNA-27 a in hypoxia is increased, while obese adipose tissue is in hypoxia area. Micro RNA-27 a has a number of downstream targets and PPAR- γ is one of them.PPAR-γ is the member of the nuclear receptor transcription factor superfamily which regulates the expression of target gene. PPAR-γ has adipose tissue specificity and can be activated by fatty acids and exogenous peroxisome proliferators expression and regulates some enzymes involved in lipid metabolism. Some studies showed that PPAR-γ protects the endothelium functions of pulmonary aorta by PPAR-γ/AKT/e NOS protein signaling pathway. Whether excessive micro RNA-27 a in obese people inhibits PPAR-γ/AKT/e NOS protein signaling pathway and reduces NO production is unclear. We want to study it.Rats were randomly divided into two groups, normal group with normal diet and high fat group with high fat diet. Establish the obesity rats model for 3 months. Exam the body weight, abdominal circumference length ratio, content of serum glucose, serum triglycerides content, the content of serum cholesterol, serum insulin levels in rats. We found that the body weight of obese rats increased significantly and abdominal circumference length ratio was significantly increased and we also found elevated serum glucose content. Serum triglyceride, serum cholesterol level are increased, serum insulin increased. The experimental results of IPGTT and ITT showed that the glucose tolerance and insulin resistance in obese rats were found. The results of insulin sensitivity index and insulin resistance index showed that there was a decrease in insulin sensitivity and a increase in insulin resistance in obese rats.Further, we detected the experimental rats serum NO, serum micro RNA-27 a content and the results showed that the obese group of rats serum NO content decreased and the serum micro RNA-27 a content increased. The results of expression of micro RNA-27 a in the aorta of experimental rats showed that the expression of micro RNA-27 a in the aorta of obese rats was increased.By Western blot technology on rat aortic vascular, PPAR-γ/AKT/e NOS signaling pathway protein expression level were detected. The results showed that obese rats PPAR-γ protein expression were inhibited, which decreased Akt and e NOS phosphorylation.Next, we performed a validation at the cellular level. We divided the cells into the con group: normal cultured; NC group: with micro RNA-27 a negative control; ROSI group: with rosiglitazone; micro RNA-27 a group: transfect micro RNA-27 a into HUVEC cells; group micro RNA-27a+rosi: transfect micro RNA-27 a into HUVEC cells and add rosiglitazone. Results showed that rosiglitazone significantly increased the NO release of HUVEC cells, and the transfection of micro RNA-27 a reduced the release of NO from HUVEC cells. Administration of rosiglitazone after transfection with micro RNA-27 a reduced NO release and reduced symptoms. At the same time, Western blot results showed that administration of rosiglitazone could significantly increase the expression level of PPAR-γ protein in HUVEC cells, and improve the downstream of Akt and e NOS phosphorylation level. Transfection micro RNA-27 a to HUVEC inhibits PPAR-γ protein expression and then inhibits the Akt and e NOS phosphorylation. Administration of rosiglitazone after transfection of micro RNA-27 a can alleviate the inhibition expression of PPAR-γ/AKT/e NOS signal pathway protein affected by micro RNA-27 a.It shows that obesity causes the increase of micro RNA-27 a secretion, and may affect the NO release function of vascular endothelium by inhibiting the PPAR-γ/AKT/e NOS protein signaling pathway in endothelial cells, which can induce vascular endothelial injury. Corresponding intervention on its downstream target PPAR-γ can reduce the impact of micro RNA-27 a. |
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