Effects Of Rosuvastatin On Cardiac Inflammation And Myocardial Fibrosis In Hypertensive Mice Induced By Ang ?

Background Hypertension refers to a clinical syndrome characterized by an increase in systemic arterial blood pressure(systolic and/or diastolic blood pressure).Hypertension is a major risk factor for many diseases such as heart failure,atrial fibrillation,chronic kidney disease,and peripheral vascular disease.Hypertension is also one of the main causes of myocardial fibrosis.After myocardial fibrosis,the balance of production and degradation of myocardial extracellular matrix is broken.The excessive accumulation of collagen fibers in normal myocardial tissue will further cause myocardial remodeling and affect the normal contraction and diastolic function of the heart,and even severe heart failure Inhibiting myocardial fibrosis,delaying and avoiding the occurrence and development of heart failure has become a major research topic in the medical.Statins are a class of compounds that block 3-hydroxy-3-methylglutaryl-Co A reductase(HMG-Co A reductase)in hepatocytes to inhibit cholesterol synthesis,thereby lowering cholesterol levels in the blood.Previous studies have shown that statins have multiple effects,besides lipid-lowering effects,they also have anti-inflammatory,antioxidant,vascular endothelial protection,plaque stabilization and immune regulation effects.It has not been reported whether statins can inhibit myocardial fibrosis induced by hypertension.In this study,animal experiments were selected,compared with cytological experiments,animal models can better mimic the pathophysiological processes of hypertension in humans and the molecular mechanisms underlying their development.Angiotensin ?(Ang ?)-induced hypertensive mouse model can replicate a large number of hypertensive models in a short period of time and can strictly control various conditions to replicate suitable for the needs of research purposes,this model has become the first choice for the study of hypertension models.Objective To investigate the effects of rosuvastatin on cardiac inflammatory cells and myocardial fibrosis markers type ? collagen and cytokines(IL-1?and TGF-?1)in Ang ?-induced hypertensive mice.Methods The ten-week-old wild-type male C57 mice were randomly divided into 4 groups,a blank control group(pumped acetic acid),a rosuvastatin intragastric group(5 mg/kg/day),and an angiotensin ? group(1,500ng/kg/min),angiotensin ? + rosuvastatin intragastric group(1,500 ng/kg/min+5 mg/kg/day).After the microosmotic pump was placed subcutaneously,the acetic acid solution and angiotensin ?(Ang ?)solution were pumped for 7 days,and rosuvastatin was administered to the stomach.The blood pressure and heart rate of the mice were measured non-invasively by mouse tail artery sleeves every day from 2 days before surgery to the 7th day after surgery.On the 7th day after surgery,the mice were anesthetized and sacrificed,and the heart was cut.HE staining was used to observe the infiltration of inflammatory cells in cardiac tissue.Masson staining was used to observe myocardial fibrosis.The expression of Collagen ?,TGF-? and IL-1? in myocardial tissue was detected by immunohistochemistry.Real time-PCR was used to detect the expression levels of Collagen ?,TGF-? and IL-1? m RNA in myocardial tissue.Results 1.After the subcutaneous angiotensin ? pump was placed in the mouse,the blood pressure began to increase 1 day after surgery,which was about 120 mm Hg.Then the blood pressure continued to rise,and it was basically stable at 160 mm Hg 4 to 7 days after the operation.2.HE staining results: Ang ? pumping increased the infiltration of perivascular inflammatory cells in the heart tissue of mice.The number of inflammatory cells in the myocardial tissue of C and D groups was significantly higher than that in A and B groups(P<0.05).There was no significant difference in the number of inflammatory cells in myocardial tissue between groups A and B(P > 0.05).The number of inflammatory cells in the myocardial tissue of group D administered with rosuvastatin was significantly lower than that in group C(P<0.05).3.Masson staining results: Ang ? pumping increased the degree of myocardial fibrosis in the heart tissue of mice.The myocardial fibrosis degree of myocardial tissue of C and D groups was higher than that of A and B groups,and the difference was statistically significant(P<0.05).The degree of myocardial fibrosis in myocardial tissue of group D mice given rosuvastatin was significantly lower than that of group C(P<0.05).4.Immunohistochemical staining results: Ang ? pumping increased the expression levels of Collagen ?,TGF-? and IL-1? in the heart tissue of mice.The expression levels of Collagen ?,TGF-? and IL-1? in the heart tissues of C and D groups were higher than those in A and B groups,and the difference was statistically significant(P<0.05).The expression of Collagen ?,TGF-? and IL-1? in the heart tissues of mice in group D administered with rosuvastatin was inhibited,which was significantly lower than that in group C(P<0.05).5.Real time-PCR results: Ang ? pumped increased the m RNA expression of Collagen ?,TGF-?1 and IL-1? in the heart tissue of mice.The m RNA expression levels of Collagen ?,TGF-?1 and IL-1? in the heart tissues of C and D groups were higher than those in A and B groups,and the difference was statistically significant(P<0.05).The m RNA expression levels of Collagen ?,TGF-?1 and IL-1? in group D mice given rosuvastatin were lower than those in group C,and the difference was statistically significant(P<0.05).Conclusions 1.Rosuvastatin can inhibit myocardial fibrosis induced by angiotensin ? in hypertensive mice.2.Rosuvastatin reduced the infiltration of inflammatory cells and the expression of Collagen ?,TGF-?1 and IL-1? in myocardial tissue of angiotensin ?-induced hypertensive mice.