In recent years, the prevalence of childhood simple obesity has been increasing year by year and is one of the most high-profile nutritional diseases in the world. Epidemiological studies have confirmed that obesity is an independent risk factor for cardiovascular diseases such as atherosclerosis (AS). Simple obesity in children not only affects the health of childhood, but is also closely related to the occurrence of many cardiovascular diseases such as diabetes, ischemic heart disease, hypertension and hyperlipidemia in adulthood.
In order to prevent and treat the cardiovascular system complications of obesity, intensive research has been conducted on the cardiovascular damage caused by obesity. Vascular endothelial cells, as the first line of defense against vascular damage, have become the core of relevant research.
Our group studied lipid metabolism, insulin resistance and cardiovascular function in children with simple obesity and found that: children with simple obesity had significant abnormalities in lipid metabolism and insulin resistance, and HDL, ApoA, blood insulin and insulin resistance index were correlated with body weight, BMI and waist circumference, and triglycerides were correlated with waist circumference and waist-to-hip ratio. Their arterial blood pressure was higher than the control group, and they had vascular endothelial dysfunction, mainly manifested by decreased reactive brachial artery dilation and overproduction of endothelin, a vascular endothelial contraction factor.
In addition, the systolic function of the heart in obese children had been affected, with higher cardiac output and higher output per beat in the obese group than in the normal control group, and lower ejection fraction and cardiac index than in the control group, but diastolic function was not found to be significantly affected. The results of this study are consistent with those of other scholars in China and abroad.
In order to understand the changes of cardiovascular ultrastructure in the obese state, an obesity model was established in young rats, and observation by electron microscopy revealed that there were breaks and numerous finger-like protrusions on the surface of vascular endothelial cells in obese young rats, and plasma protein attachments were seen, and this process is one of the key factors of atherosclerosis. In addition to this, migration of smooth muscle cells to the subintima was observed. Smooth muscle cell proliferation and subendothelial migration are the main pathological features of atherosclerosis, suggesting significant ultrastructural alterations in the vascular endothelium of obese young rats.
What is the mechanism of obesity-induced vascular endothelial injury? Scholars at home and abroad have concluded that, in addition to lipid metabolism disorder, insulin resistance and oxidative stress, adipokines also have an important regulatory role on the function and structure of blood vessels. Therefore, a newly discovered adipokine “resistin” was used to study the mechanism of damage to NO system, which is a vasodilatory factor, and it was found that resistin has a clear effect on the cellular activity of aortic endothelial cells and NO system.
The results showed that resistin had a clear effect on the cellular activity of aortic endothelial cells and NO system.
The detection of NO system indicators revealed that NO release was not significantly altered in all groups, and total NOS and eNOS activities were not significantly altered. In addition to the NO system, resistin can cause vascular endothelial cell injury through oxidative stress, increased ET expression, and decreased tumor necrosis factor (TNF) receptor-associated factor (TRAF)-3 secretion.
Resistin can downregulate the expression of eNOS protein and mRNA, and resistin may decrease eNOS protein expression by downregulating eNOS mRNA expression. It is speculated that NO and NOS activity were not affected because NO and NOS are regulated by multiple complex mechanisms, and resistin may have affected other cytokines to indirectly antagonize the reduced activity caused by decreased eNOS protein expression, leaving eNOS activity unaffected.
The expression of P-eNOS was not significantly altered by resistin between the groups. It is speculated that the regulatory effect of resistin on eNOS may not be achieved through phosphorylation. Some of the results of this study are consistent with related domestic and international studies, but the present study is the first to provide a comprehensive and in-depth mechanistic description.
All of the above studies show that obesity has a clear effect on vascular endothelium damage, therefore, prevention of obesity and effective treatment of obesity are important to prevent vascular endothelial damage.
Investigation of the diet and living habits of simple obese children found that: obese children usually eat more, the diet structure is unreasonable, prefer sweet food, meat food, poor eating habits, like to eat snacks and the bad habit of eating before bedtime, at the same time, the amount of activity is low, so that the calorie supply is too much and consumption is less, transformed into fat in the body deposition, is the main factor for obesity. Analysis of the obesity status of the parents of the children found that the proportion of obese children with two parents and/or one parent is significantly higher than that of healthy children, and genetic genes may also play an important role.
Recently, the study subjects were intervened by insisting on following diet control, moderate exercise and changing bad habits to understand the changes of some physical data before and after the intervention. Most of the children achieved varying degrees of success, but still did not reach the level of the control group during the follow-up time, indicating that exercise and diet regulation is a fairly long process, and we also believe that obese children must not be forced to reduce their weight index to normal levels.
The incidence of obesity is increasing year by year, and diet control and exercise are the more recognized methods of weight loss, but even adults are mostly unable to adhere to and achieve the purpose of weight loss, and children are even more difficult to achieve. The protective effect of drugs on vascular endothelial injury in obese patients has therefore received attention.
In this study, niacin and the Chinese herbal medicine Tanshinone IIA were selected for early intervention in obese young rats at different doses, and some lipid metabolic indexes, vascular endothelial factors and changes in cardiovascular ultrastructure under electron microscopy were detected.
Both adequate doses of Tanshinone IIA and low-dose niacin had good effects on regulating lipid metabolism and could reduce serum levels of TG, Tch, LDL-C and VLDL to different degrees and increase HDL-C levels, the latter effect being more significant. HDL-C is a cardiovascular protective factor with anti-AS formation effect, while TG, Tch, LDL-C, VLDL levels and AS were positively correlated. Therefore, these two drugs can reduce the risk of vascular endothelial injury by regulating lipid metabolism.
IGF-1 is an active protein peptide substance with vasodilatory effect. Niacin and tanshinone IIA were not found to alter IGF-1 expression levels within the studied doses.
The balance of TXA2 and PGI2 ratio is an important link to maintain normal vascular function and protect endothelial cells from damage. Since TXA2 and PGI2 are extremely unstable in plasma, TXB2 and 6-keto -PGF1a levels are usually measured to reflect the levels of TXA2 and PGI2. In the high-fat control group, TXB2 levels were significantly higher and 6-keto-PGF1a was significantly lower compared with the normal group, reflecting increased synthesis and release of the vasoconstrictor TXA2 and decreased synthesis of PGI2, and damaged vascular endothelial cells in the high-fat group of rats.
TXB2 levels were significantly reduced in the intervention groups of both drugs compared with the control group, with more significant changes in the low-dose group. The levels of 6-Keto-PGFla were significantly increased in all dose groups of tanshinone IIA with respect to and in the high dose group of niacin compared with the control group. This indicates that these two drugs have a regulatory effect on the imbalance of TXA2 and PGI2 ratio, thus achieving the purpose of protecting the vascular endothelium.
The pathomorphological changes in each group were observed by light and electron microscopy, and it was found that: both drugs significantly reduced the degree of myocardial and vascular endothelial damage in the low and medium dose groups compared with the high-fat control group. It is suggested that: niacin and tanshinone IIA have a clear preventive effect on obesity-induced cardiovascular injury.
The present study confirmed the existence of lipid metabolism disorder, insulin resistance and cardiovascular impairment in children with simple obesity through numerous clinical studies, and morphologically observed the existence of vascular endothelial damage in animal models of obesity, and then investigated the molecular biological mechanism of damage to the NO system of adipokines “resistin” and vasodilators for the first time from multiple levels. The molecular biological mechanism of the damage of the adipokine “resistin” and vasodilator NO system was studied for the first time.
Through the clinical investigation of simple obese children, we understand the relationship between their dietary habits and the development of obesity and provide comprehensive interventions to explore the methods to reduce the degree of obesity, and propose for the first time that niacin and tanshinone IIA can prevent the damage of cardiovascular system caused by obesity. It will help to provide early therapeutic targets for the prevention and treatment of obesity and cardiovascular lesions.
Further clinical trials are needed to explore how to use serum resistin levels as an indicator for assessing the extent of endothelial cell injury and how to apply both niacin and tanshinone IIA in humans, especially in children.