ABSTRACT
Obesity-related hypertension is a common hypertension as well as a common chronic disease with wide distribution and great harm to human health. In recent years, this disease has become one of the hot issues of public health due to the significant increase in prevalence. The pathogenesis and pathway of obesity-related hypertension are not yet clear, and the research on its pathogenesis has received extensive attention. Studies have shown that they are regulated in most biological processes, including differentiation, proliferation, migration, and apoptosis. The miR-200 family is a group of miRNAs, which have been suggested to play a crucial role in obesity-related hypertension and glucolipid metabolism dysfunction in recent years. This paper reviews relevant research results, suggesting that the expression level of miR-200 family in obese patients with hypertension is higher than that in healthy people, which regulates the occurrence and development of hypertension through mediating oxidative stress response and GATA expression level. This review reveals the relationship between miR-200 family and obesity-related hypertension, which offers new clues to explore potential therapeutic targets for obesity-related hypertension.
ABSTRACT
ObjectiveTo explore the effect of Qinggan Zishen prescription on metabolic disorders in obesity-related hypertension （OBH） patients and analyze the potential pharmacological mechanism based on network pharmacology. MethodA total of 85 eligible OBH patients who were treated in the outpatient or wards of Jiangsu Province Hospital of Chinese medicine from September 2018 to January 2020 were selected and randomized into the observation group （45 cases） and control group （40 cases）. All patients were treated with western medicine during a four-week introduction period， and then the observation group was treated with Qinggan Zishen prescription on the basis of western medicine. The study lasted 6 months， and indicators， such as triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， glycosylated hemoglobin （HbA1c）， fasting blood glucose （FBG）， fasting insulin （FINS）， waist circumference （W）， hip circumference （H） were detected and homeostasis model assessment of insulin resistance （HOMA-IR），body mass index （BMI）， waist-hip ratio （WHR） were calculated before and after intervention. At the same time， the regulation network of the Qinggan Zishen prescription was visualized and the protein-protein interaction （PPI） network was constructed. The core targets of the network were obtained for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. ResultAfter intervention for 6 months， the levels of W， H， WHR， FINS， and HOMA-IR in the observation group were reduced as compared with those in the control group （P<0.05， P<0.01）. According to network pharmacology， the main components of Qinggan Zishen prescription in treating OBH were luteolin， quercetin， and berberine and the key targets were amyloid precursor protein （APP）， vascular endothelial growth factor A （VEGFA）， and estrogen receptor 1 （ESR1）. Moreover， the key biological pathway was advanced glycation end product （AGE）/advanced glycation end product receptor （RAGE） signaling pathway. ConclusionQinggan Zishen prescription can improve the metabolic disorder of OBH patients through multiple components， multiple targets， and multiple pathways， which provides new mindset for follow-up studies.
ABSTRACT
Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.
Subject(s)
Animals , Male , Adrenomedullin , Metabolism , Blood Pressure , Physiology , Hypertension , Lipopolysaccharides , Pharmacology , Neuropeptides , Metabolism , Obesity , Rats, Sprague-Dawley , Receptors, Adrenomedullin , Metabolism , Sympathetic Nervous System , Metabolism , Toll-Like Receptor 4 , MetabolismABSTRACT
Objective: To observe the effect and explore the mechanism of Tribulus terrestris (TT) on kidney of rats with obesity-related hypertension through leptin mediated JAK2/STAT3 pathway. Methods: To establish the model of rats with obesity-related hypertension by high-fat diet. The model rats were randomly divided into three groups: TT group (eight rats, 17.2 g/kg), Telmisartan group (eight rats, 3.4 mg/kg), and model group (eight rats, normal saline 2 mL/d). Rats were ig given drugs or saline for 12 weeks. The body weights and blood pressure were measured regularly. At the end of the study, the rats were sacrificed and the levels of serum lipid and angiotensinII (AngII) and β2-microglobulin (β2-MG) were determined by ELISA. Morphological changes of adipose tissue and kidney were observed by HE staining. The density of LepR in kidney was observed by immunohistochemical staining. Levels of mRNA and protein expression of JAK2 and STAT3 in kidney were determined by quantitive real-time PCR (qRT-PCR) and Western blotting. Results: Both body weights and blood pressure of TT group were decreased (P < 0.05). The levels of serum TG, TC, and LDL-C of TT group were decreased significantly (P < 0.05). Kidney morphology of TT group was improved obviously and the size of lipocyte decreased. The levels of serum Ang II, Lep, and β2-MG of TT group decreased significantly (P < 0.05). The density of LepR in kidney of TT group decreased significantly (P < 0.05). The mRNA and protein expression of JAK2 and STAT3 in kidney of TT group was decreased significantly (P < 0.05). Conclusion: TT improves the leptin resistance of the obesity-related hypertensive rats mainly through JAK2/STAT3 pathway.
ABSTRACT
Obesity is the most important risk factor of primary hypertension. Rapid increase of obesity-related hypertension has become a worldwide problem. But the specific mechanism of the condition remains to be fully understood. This paper reviews the latest literatures and tries to explain the mechanism of obesity-related hypertension from the following four aspects: hypoadiponectinemia, leptin and resistance of leptin, insulin and resistance of insulin and the activation of renin-angiotensin system(RAS).